Background: Human adenoviruses (HAdVs) are extensively used as vectors for vaccines development and cancer therapy. People who already have antibodies against HAdVs, on the other hand, would have an impact on the preventative or therapeutic effect. This review focuses primarily on the prevalence of pre-existing antibodies against HAdVs in distinct geographical populations. Summary: After screening, 64 studies from 31 countries between 1962 and 2021 were selected, totaling 39,427 samples. The total prevalence of preexisting antibodies to HAdVs varied by country or location, ranging from 2.00 to 95.70%. Southeast Asia had the highest prevalence (54.57%) while Europe had the lowest (18.17%). The prevalence in practically all developing nations was higher than in developed nations. Adults have a greater frequency than children and newborns in most nations. The primary HAdV antibody types varied by country. Adults in China, the USA, the United Kingdom, and Belgium had the lowest prevalence of preexisting antibodies against HAdV55, HAdV37, HAdV8, and HAdV36, respectively. Children in the USA, China, the United Kingdom, and Japan had the lowest rates of HAdV48, HAdV11, HAdV8, and HAdV40. The frequency of antibodies differed significantly between military and civilian groups. Key Messages: Preexisting antibodies against various types of HAdVs differed greatly throughout worldwide populations. Future development of HAdV-vector vaccines and medicines should focus on preexisting antibodies in target groups rather than a “one-size-fits-all” strategy. It might be advantageous in selecting HAdV vectors for studying the prevalence of preexisting antibodies against HAdVs in different locations and people throughout the world.

Adenoviruses (AdVs) are a group of double-stranded linear DNA viruses without envelopes that belong to the family Adenoviridae [1]. They were first cultured and identified in 1953 from human adenoid tissue [2]. Since then, AdVs have been identified in a range of animals and humans. Currently, there are more than 100 serotypes of AdVs, which are divided into 7 subgroups (A-G). Among them, more than 60 types are specifically human adenoviruses (HAdVs). HAdVs have the ability to infect humans through multiple pathways, including the respiratory, gastrointestinal, urinary, or ocular tracts. They have the ability to invade organs such as the bladder, liver, or brain, causing a variety of diseases [3‒5]. The most common routes of infection are through the respiratory and gastrointestinal tracts.

With advancements in genetic engineering technology, AdVs have been utilized as gene expression vectors due to their broad host range and low pathogenicity in humans [6]. AdV-vector vaccines have been extensively employed in preventing various viral infections, including Ebola, hepatitis B, hepatitis C, and influenza virus [7‒10]. During the COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several vaccines based on AdV vectors have been developed and utilized [11‒13]. For example, the Gam-COVID-Vac (Sputnik V) COVID-19 vaccine was developed by the Gamaleya Research Institute of Epidemiology and Microbiology using replication-deficient adenovirus (rAdV) 26 and rAdV5 vectors [14]. Likewise, the Janssen pharmaceutical company developed the Ad26.COV2.S vaccine, which utilized the rAdV26 vector encoding the full-length wild-type SARS-CoV-2 spike protein [15]. CanSino Biologics and the Beijing Institute of Biotechnology also developed the Ad5-nCoV vaccine, an AdV-vectored vaccine using the rAdV5 vector [16]. Additionally, the University of Oxford and AstraZeneca developed the ChAdOx1 nCoV-19 vaccine, utilizing a chimpanzee AdV-vector called ChAdOx1 [17]. These recombinant AdV-vector vaccines involve the insertion of exogenous antigen genes into the Adv genome, enabling the expression of the target protein in the body, thereby inducing antibody production upon vaccination.

In addition to the development of vaccines, AdVs have been genetically modified for potential tumor treatments. AdVs have a natural affinity for epithelial cells, which make up the majority of human tumors. Through artificial modifications, AdVs can be transformed into oncolytic viruses designed to recognize and infect tumor cells while sparing normal cells in the body [18, 19]. Moreover, AdVs can be utilized as targeted drug carriers for delivering therapeutic drugs directly to tumor cells, aiding in tumor therapy [20]. Currently, numerous clinical worldwide are underway for AdV-associated oncolytic viruses or drug vectors. These novel therapeutic approaches target a wide range of tumors, including glioma, colon, melanoma, and bladder cancer [20].

However, HAdVs are widespread worldwide and can lead to outbreaks throughout the year [4, 21]. Humans are highly susceptible to HAdVs and can develop specific antibodies following infection, which generate preexisting immunity against future HAdV infections. Preexisting immunity refers to the existing level of neutralizing antibodies and specific cellular immunity acquired from previous infections. This preexisting immunity can have an impact on the effectiveness of AdV-vector vaccinations or therapies. Since the prevalence of neutralizing antibodies against HAdVs in populations can significantly influence the preventive or therapeutic effects of AdV-vector vaccines or drugs, it is crucial to investigate the prevalence of antibodies against specific types of HAdVs in the population prior to their applications.

Immunocompetent individuals typically experience mild symptoms and recover spontaneously after HAdV infection, while individuals with suppressed immune function often have severe outcomes [22, 23]. As a result, antibodies against HAdVs can be found in the blood of both diseased and non-diseased populations. Asymptomatic HAdV infections may lead to an underestimation of antibodies in populations. Additionally, the prevalence of HAdVs antibodies can increase due to vaccination with AdV vaccines. For instance, the United States of America (USA) developed oral vaccines for HAdV4 and HAdV7, which were vaccinated to military recruits [24‒27]. Given the numerous HAdV types and their varying prevalence in different geographic areas and populations, it is challenging to investigate the prevalence of antibodies against each type individually. Therefore, this study aims to determine the global prevalence of preexisting antibodies against various types of HAdVs in different areas and populations by reviewing relevant literature on AdV-vector vaccines and drug development and application.

Data Collection

Literatures published in databases of PubMed, Web of Science, Elsevier, Ovid, and China National Knowledge Infrastructure (CNKI) before May 17, 2021, were searched and screened. The search technique was adjusted in various databases based on different search criteria. The keywords included: “Adenovirus*,” “prevalence*,” “seroprevalence*,” “antibody*,” and “neutralization”. Asterisks indicated wildcard characters. One reviewer independently checked out titles and abstracts, followed by another independent reviewer who screened entire texts.

Inclusion Criteria

Studies were included after screening but were considered to be excluded in our analysis if they were: (1) duplicate articles, where the same document appeared multiple times in different databases; (2) the same samples, where studies that used data from the same population; (3) no needed data meant that the study does not have the required data; (4) articles not written in English or Chinese languages; (5) studies focused on non-human subjects and excluding nonanimal studies; (6) studies primarily dealing with diseases rather than examining the prevalence of antibodies; (7) studies primarily dealing with diseases rather than examining the prevalence of antibodies; (8) studies specifically investigating the phylogenetic distance, genome organization, or nucleotide composition of HAdVs; (9) Studies primarily focused on AdV-vector vaccines; (10) studies primarily emphasizing other genera within the Adenoviridae family rather than HAdVs; (11) studies providing only data on HAdVs infection without addressing the prevalence of antibodies; (12) editorial articles.

Data Extraction

The variables that were extracted for analysis encompassed the following aspects: authors of the studies, publication year, country, study date, study design, characteristics of the population under investigation, age distribution, specimen type used for testing, sample size, number of positive cases detected, prevalence rate, detection method employed, and specific serotypes of interest.

Country Classification

Based on the 2021/2022 Human Development Report, the countries included in this study were classified into two categories: developed and developing. According to the report, out of the 38 member countries of the Organization for Economic Co-operation and Development (OECD), only 33 are categorized as developed countries. The remaining countries, which include five OECD’s members (Costa Rica, Chile, Colombia, Mexico, and Turkey) are classified developing countries. Refer to Supplementary Table 1 (for all online suppl. material, see https://doi.org/10.1159/000538233) for an overview of the country classifications used in this analysis.

Statistical Analysis

To analyze the prevalence of HAdVs in different countries and populations, the study employed the χ2 test or Fisher’s exact test (when sample size was small). The statistical software used for programming was R 4.03 (The R Foundation for Statistical Computing, Vienna, Austria). A p value threshold of <0.05 was considered statistically significant. Geographical distribution maps were generated using ArcGIS 10.2.0 for visualization purposes.

Figure 1 illustrated the process of article selection for the analysis. Initially, a total of 921 articles were collected from different databases. Following the application of exclusion criteria (online suppl. Tables 2), 64 articles were deemed suitable for inclusion in the analysis. The publication years of the included articles ranged from 1962 to 2021, with a significant proportion (60.94%) published between 2011 and 2021. This observation suggests a heightened interest in preexisting antibodies of HAdVs in recent years. Based on the regional classification by the World Health Organization (WHO), the distribution of articles was as follows: Western Pacific (42.19%), Americas (26.56%), Europe (18.75%), Eastern Mediterranean (6.25%), Africa (4.69%), Southeast Asia (3.13%), and 2 articles (3.13%) that did not specify the region where the samples were collected (Fig. 2). Overall, the included articles reported a total of 39,427 samples, among which 17,257 cases were seropositive for HAdVs.

Fig. 1.

The flowchart of studies screening and inclusion.

Fig. 1.

The flowchart of studies screening and inclusion.

Close modal
Fig. 2.

Geographic distribution of included studies by regions. The depth of the blue gradient represented the number of articles included in each region, and the gray area indicated that there was no relevant literature for that region.

Fig. 2.

Geographic distribution of included studies by regions. The depth of the blue gradient represented the number of articles included in each region, and the gray area indicated that there was no relevant literature for that region.

Close modal

Prevalence of Preexisting HAdVs Antibodies by Regions

According to Table 1, the prevalence of antibodies against different types of HAdVs in 31 countries or areas ranged from 2.00% to 95.70%. Among the regions, Southeast Asia had the highest median prevalence (54.57%), followed by Eastern Mediterranean (43.31%), Western Pacific (42.40%), Africa (35.48%), and the Americas (24.02%). In contrast, Europe had the lowest median prevalence of 18.17%. It was worth noting that Europe primarily consisted of developed countries, while the Eastern Mediterranean and Africa regions were developing countries (online suppl. Table 2). Additionally, the prevalence in the Western Pacific was higher than that in the Americas (42.40 vs. 24.02%, p < 0.05).

Table 1.

Prevalence of HAdVs antibodies by regions

RegionsCountries or areasDevelopmentReports (n)Sample (n)Prevalence (%)Median (IQR*) (%)Reference
Africa 3,920 2.00–90.80 35.48 (12.80, 68.92) 
 Africa 199 7.54–83.42 32.16 (18.09, 52.89) Barouch et al. [28] (2011) 
 Gambia Developing 50 2.00–84.00 43.00 (22.50, 63.50) Nwanegbo et al. [29] (2011) 
 Kenya Developing 263 14.83–90.49 58.55 (41.92, 72.24) Barouch et al. [28] (2011) 
 Sierra Leone Developing 498 69.30–90.80 80.05 (74.68, 85.43) Wang et al. [30] (2018) 
 South Africa Developing 2,668 5.37–79.25 14.54 (12.27, 38.27) Barouch et al. [28] (2011), Nwanegbo et al. [29] (2011), Thorner et al. [31] (2006), Chapple et al. [32] (1966) 
 Uganda Developing 242 5.00–86.36 58.89 (38.84, 72.42) Barouch et al. [28] (2011) 
Eastern Mediterranean 1,596 30.58–49.07 43.31 (39.37, 47.07) 
 United Arab Emirates Developing 973 47.07 Lessan et al. [33] (2020) 
 Iran Developing 127 39.37–43.31 41.34 (40.36, 42.33) Saderi et al. [34] (2000) 
 Saudi Arabia Developing 375 49.07 Hossain et al. [35] (1988) 
 Tunisia Developing 121 30.58 Chapple et al. [32] (1966) 
Europe 12 8,136 4.46–55.95 18.17 (8.02, 24.36) 
 Belgium Developed 250 6.00 Goossens et al. [36] (2011) 
 Czechia Developed 1,179 26.46 Aldhoon et al. [37] (2014) 
 Germany Developed 850 6.16–29.80 19.05 (11.32, 24.07) Sester et al. [38] (2002), Jung et al. [39] (1967) 
 Netherlands Developed 259 5.02 Goossens et al. [36] (2011) 
 Norway Developed 1,268 24.50 Omenaas et al. [40] (1995) 
 Sweden Developed 3,676 13.14–18.17 15.66 (14.40, 16.91) Almgren et al. [41] (2012), Almgren et al. [42] (2014) 
 Turkey Developing 458 7.52–16.30 12.20 (9.86, 14.25) Ergin et al. [43] (2015), Karamese et al. [44] (2015), Kocazeybek et al. [45] (2017) 
 United Kingdom Developed 196 4.46–55.95 45.24 (24.85,50.60) Chapple et al. [32] (1966), Potter et al. [46] (1963) 
Southeast Asia 508 12.79–91.43 54.57 (17.12, 82.19) 
 India Developing 70 91.43 Appaiahgari et al. [47] (2007) 
 Thailand Developing 438 12.79–82.19 35.85 (16.04, 82.19) Barouch et al. [28] (2011) 
The Americas 20 8,056 2.53–77.66 24.02 (12.99, 37.81)  
 Brazil Developing 417 15.84–69.5 22.25 (18.18, 38.88) Ersching et al. [48] (2010), Cancelier et al. [49] (2021), Weinberg et al. [50] (1989) 
 Chile Developing 250 48.80 Sapuna et al. [51] (2020) 
 Jamaica Developing 510 53.92 Jennings et al. [52] (1972) 
 Mexico Developing 157 73.89 Parra-Rojas et al. [53] (2013) 
 North/South America 405 7.65–51.85 20.50 (13.58, 32.04) Barouch et al. [28] (2011) 
 The USA Developed 14 6,317 2.53–77.66 19.67 (10.48, 35.89) Barouch et al. [28] (2011), Nwanegbo et al. [29] (2011), Chapple et al. [32] (1966), Ludwig et al. [54] (1998), Rubicz et al. [55] (2011), Curlin et al. [56] (2011), Crawford-Miksza et al. [57] (1996), Rosen et al. [58] (1962), Buchwald et al. [59] (1996), Gabbert et al. [60] (2010), Broderick et al. [61] (2010), Berger et al. [62] (2014), Atkinson et al. [63] (2005), Tosh et al. [64] (2017) 
Western Pacific 26 15,355 5.85–91.10 42.40 (22.40, 63.82) 
 China Developing 22 13,838 5.85–91.10 43.07 (22.38, 67.82) Wang et al. [30] (2018), Zhou et al. [65] (2018), Yang et al. [66] (2016), Wang et al. [67] (2014), Zhang et al. [68] (2013), Yu et al. [69] (2012), Ye et al. [70] (2018), Tian et al. [71] (2021), Zhao et al. [72] (2018), Zheng et al. [73] (2017), Huang et al. [74] (2015), Yu et al. [75] (2012), Chen et al. [76] (2017), Sun et al. [77] (2011), Li et al. [78] (2017), Liu et al. [79] (2018), Zhao et al. [80] (1995), Su et al. [81] (2007), Li [82] (2018), Sheng et al. [83] (2013), Zhu et al. [84] (2016), Lu et al. [85] (2011) 
 Japan Developed 528 16.20–42.23 24.65 (20.43, 33.44) Iwaya et al. [86] (1995), Shinozaki et al. [87] (1987) 
 Malaysia Developing 160 45.00 Chapple et al. [32] (1966) 
 Marshall Islands Developing 93 54.84 Chapple et al. [32] (1966) 
 South Korea Developed 736 34.26–59.18 37.76 (36.01, 48.47) Park et al. [88] (2020), Na et al. [89] (2012) 
Unknown 1,555  
 Unknown 1,482 41.43 Kazakova et al. [90] (2012) 
 Unknown 73 23.30 Vander et al. [91] (2013) 
Overall 64 39,126 2.00–91.43 27.39 (13.59, 51.85) 
RegionsCountries or areasDevelopmentReports (n)Sample (n)Prevalence (%)Median (IQR*) (%)Reference
Africa 3,920 2.00–90.80 35.48 (12.80, 68.92) 
 Africa 199 7.54–83.42 32.16 (18.09, 52.89) Barouch et al. [28] (2011) 
 Gambia Developing 50 2.00–84.00 43.00 (22.50, 63.50) Nwanegbo et al. [29] (2011) 
 Kenya Developing 263 14.83–90.49 58.55 (41.92, 72.24) Barouch et al. [28] (2011) 
 Sierra Leone Developing 498 69.30–90.80 80.05 (74.68, 85.43) Wang et al. [30] (2018) 
 South Africa Developing 2,668 5.37–79.25 14.54 (12.27, 38.27) Barouch et al. [28] (2011), Nwanegbo et al. [29] (2011), Thorner et al. [31] (2006), Chapple et al. [32] (1966) 
 Uganda Developing 242 5.00–86.36 58.89 (38.84, 72.42) Barouch et al. [28] (2011) 
Eastern Mediterranean 1,596 30.58–49.07 43.31 (39.37, 47.07) 
 United Arab Emirates Developing 973 47.07 Lessan et al. [33] (2020) 
 Iran Developing 127 39.37–43.31 41.34 (40.36, 42.33) Saderi et al. [34] (2000) 
 Saudi Arabia Developing 375 49.07 Hossain et al. [35] (1988) 
 Tunisia Developing 121 30.58 Chapple et al. [32] (1966) 
Europe 12 8,136 4.46–55.95 18.17 (8.02, 24.36) 
 Belgium Developed 250 6.00 Goossens et al. [36] (2011) 
 Czechia Developed 1,179 26.46 Aldhoon et al. [37] (2014) 
 Germany Developed 850 6.16–29.80 19.05 (11.32, 24.07) Sester et al. [38] (2002), Jung et al. [39] (1967) 
 Netherlands Developed 259 5.02 Goossens et al. [36] (2011) 
 Norway Developed 1,268 24.50 Omenaas et al. [40] (1995) 
 Sweden Developed 3,676 13.14–18.17 15.66 (14.40, 16.91) Almgren et al. [41] (2012), Almgren et al. [42] (2014) 
 Turkey Developing 458 7.52–16.30 12.20 (9.86, 14.25) Ergin et al. [43] (2015), Karamese et al. [44] (2015), Kocazeybek et al. [45] (2017) 
 United Kingdom Developed 196 4.46–55.95 45.24 (24.85,50.60) Chapple et al. [32] (1966), Potter et al. [46] (1963) 
Southeast Asia 508 12.79–91.43 54.57 (17.12, 82.19) 
 India Developing 70 91.43 Appaiahgari et al. [47] (2007) 
 Thailand Developing 438 12.79–82.19 35.85 (16.04, 82.19) Barouch et al. [28] (2011) 
The Americas 20 8,056 2.53–77.66 24.02 (12.99, 37.81)  
 Brazil Developing 417 15.84–69.5 22.25 (18.18, 38.88) Ersching et al. [48] (2010), Cancelier et al. [49] (2021), Weinberg et al. [50] (1989) 
 Chile Developing 250 48.80 Sapuna et al. [51] (2020) 
 Jamaica Developing 510 53.92 Jennings et al. [52] (1972) 
 Mexico Developing 157 73.89 Parra-Rojas et al. [53] (2013) 
 North/South America 405 7.65–51.85 20.50 (13.58, 32.04) Barouch et al. [28] (2011) 
 The USA Developed 14 6,317 2.53–77.66 19.67 (10.48, 35.89) Barouch et al. [28] (2011), Nwanegbo et al. [29] (2011), Chapple et al. [32] (1966), Ludwig et al. [54] (1998), Rubicz et al. [55] (2011), Curlin et al. [56] (2011), Crawford-Miksza et al. [57] (1996), Rosen et al. [58] (1962), Buchwald et al. [59] (1996), Gabbert et al. [60] (2010), Broderick et al. [61] (2010), Berger et al. [62] (2014), Atkinson et al. [63] (2005), Tosh et al. [64] (2017) 
Western Pacific 26 15,355 5.85–91.10 42.40 (22.40, 63.82) 
 China Developing 22 13,838 5.85–91.10 43.07 (22.38, 67.82) Wang et al. [30] (2018), Zhou et al. [65] (2018), Yang et al. [66] (2016), Wang et al. [67] (2014), Zhang et al. [68] (2013), Yu et al. [69] (2012), Ye et al. [70] (2018), Tian et al. [71] (2021), Zhao et al. [72] (2018), Zheng et al. [73] (2017), Huang et al. [74] (2015), Yu et al. [75] (2012), Chen et al. [76] (2017), Sun et al. [77] (2011), Li et al. [78] (2017), Liu et al. [79] (2018), Zhao et al. [80] (1995), Su et al. [81] (2007), Li [82] (2018), Sheng et al. [83] (2013), Zhu et al. [84] (2016), Lu et al. [85] (2011) 
 Japan Developed 528 16.20–42.23 24.65 (20.43, 33.44) Iwaya et al. [86] (1995), Shinozaki et al. [87] (1987) 
 Malaysia Developing 160 45.00 Chapple et al. [32] (1966) 
 Marshall Islands Developing 93 54.84 Chapple et al. [32] (1966) 
 South Korea Developed 736 34.26–59.18 37.76 (36.01, 48.47) Park et al. [88] (2020), Na et al. [89] (2012) 
Unknown 1,555  
 Unknown 1,482 41.43 Kazakova et al. [90] (2012) 
 Unknown 73 23.30 Vander et al. [91] (2013) 
Overall 64 39,126 2.00–91.43 27.39 (13.59, 51.85) 

*IQR, interquartile range.

Investigations conducted in Africa revealed a wide range in the prevalence of 9 HAdVs types across 5 countries ranging from 2.00% to 90.80% (Table 1) [28‒32]. Sierra Leone exhibited the highest median prevalence at 80.05%, whereas South Africa had the lowest median prevalence at 14.54% [28‒32]. The prevalence of HAdV5 in Sierra Leone was the highest among all African countries at 90.80% [30]. Conversely, Gambia reported the lowest prevalence of HAdV35 at 2.00% [29]. In a study conducted in 2011, the prevalence of 4 HAdV types (HAdV5, HAdV26, HAdV35, and HAdV48) was assessed in 3 countries (South Africa, Kenya, Uganda). The results from these countries showed that HAdV5 had the highest prevalence, followed by HAdV26, HAdV48, and HAdV35 (p < 0.05) [28].

In the Eastern Mediterranean region, studies conducted in United Arab Emirates, Iran, Saudi Arabia, and Tunisia reported the prevalence of preexisting antibodies against HAdVs, ranging from 30.58% to 49.07% (Table 1) [32‒35]. The identified HAdV types included HAdV8, HAdV36, HAdV40, and HAdV41. Saudi Arabia exhibited the highest prevalence at 49.07% the 4 countries, although the specific serotypes of these HAdVs were not specified [35]. Tunisia had the lowest prevalence at 30.58%, while United Arab Emirates reported a prevalence of 47.07% [32, 33]. Iran only provided data on the prevalence of antibodies against two HAdV types, with a prevalence of 43.31% for HAdV40 and 39.37% for HAdV41 [34].

In Europe, a total of 15 types of HAdVs were studied in 8 countries, revealing a wide range of prevalence of antibodies, from 4.46% to 55.95% (Table 1). A majority of the studies (7 out of 12, 58.33%) focused on investigating the prevalence of HAdV36, which ranged from 5.02 to 26.46%. Two studies from Norway and Germany did not specify the types of HAdVs investigated [38, 40]. However, a German study reported the prevalence of antibodies against 12 HAdV types, with HAdV9 having the highest prevalence (29.80%) and HAdV15 having the lowest prevalence (6.16%) [39]. In the United Kingdom (UK), three HAdVs (HAdV1, HAdV3, and HAdV8) were reported, with a median prevalence of 45.84% among the 8 countries [32, 46]. The Netherlands had the lowest prevalence of antibodies against HAdV36 at 5.02% [36]. As the only developing country in Europe, Turkey had a median prevalence of 12.20% [45].

In Southeast Asia, only 2 articles from India and Thailand were included in the study. The prevalence of antibodies against HAdVs in this region ranged from 12.79% to 91.43% (Table 1) [28, 47]. In India, a high prevalence of antibodies against HAdv5 was reported at 91.43% [47]. In Thailand, antibodies against 4 HAdV types were detected, with the highest prevalence seen for HAdV5 at 82.19%, followed by HAdv26 (54.57%), HAdv35 (17.12%), and HAdv48 (12.79%) (p < 0.05) [28].

In the Americas, the study included data from five countries and reported prevalence rates for ten different types of HAdVs (Table 1). The prevalence of HAdV36 in Mexico was the highest among the 5 countries at 73.89% [53]. The median prevalence rates in Jamaica, Chile, and Brazil were 53.92%, 48.80%, and 22.25%, respectively [48‒52]. The USA had a median prevalence rate of 19.67%, which was lower compared to the other countries in the region. Among the 8 types of HAdVs reported in the USA, HAdV35 had the lowest prevalence at 6.33%, followed by HAdV27 at 7.00% [29, 58]. The prevalence of HAdV5 in both Brazil and the USA remained higher compared to the other types [29, 48, 56].

In the Western Pacific region, data from five countries revealed a range in prevalence rates of antibodies against 12 different HAdV types, from 5.85% to 95.70% (Table 1). Among these countries, Japan, as a developed country, had the lowest median prevalence rate of 24.65% [86, 87]. The highest median prevalence rate was observed in Marshall Islands at 54.84%, followed by Malaysia (45.00%), China (43.07%), and South Korea (37.76%). Most of the studies and samples from the Western Pacific region were conducted in China, where 11 types of HAdVs were reported [30, 65‒85]. In China, HAdV55 had the lowest prevalence rate at 5.85%, while HAdV2 had the highest prevalence rate at 91.10% [70, 71]. The prevalence of antibodies against HAdV5 was higher compared to HAdV4 and HAdV26 but lower compared to HAdV2 and HAdV41 (p < 0.05).

Prevalence of HAdVs Antibodies in Different Periods

The analysis of the prevalence of preexisting antibodies during different periods grouped the years 1962–2000 as the first period, followed by 2001–2010 and 2011–2020 as the second and third periods, respectively (Table 2). The number of studies conducted in these three periods was 15, 9, and 40, respectively. During the first period, HAdV4 and HAdV8 were frequently reported, while HAdV5 and HAdV36 were more commonly reported in the latter two periods [32, 39, 53‒56, 80‒82]. Most countries only had studies in one of the periods, with only Brazil, China, South Africa, and the USA having studies spanning all three periods (Fig. 3). Brazil had similar median prevalence in the first third periods, but significantly higher prevalence in the second period [48‒50]. In contrast, South Africa showed a small difference in prevalence between the first and third periods, but much lower prevalence in the second period [28, 29, 31, 32]. Both China and the USA exhibited an upward trend in prevalence across the three periods.

Table 2.

Prevalence of HAdVs antibodies by regions in different periods

Countries1962–20002001–20102011–2021
prevalence (%)median (%)prevalence (%)median (%)prevalence (%)median (%)
Africa 7.54–83.42 32.16 
Gambia 2.00–84.00 43.00 
Kenya 14.83–90.49 58.56 
Sierra Leone 69.30–90.80 80.05 
South Africa 30.00 6.00–79.87 13.27 12.15–79.1 28.20 
Uganda 5.37–86.36 58.89 
United Arab Emirates 47.10 
Iran 39.37–43.31 41.34 
Saudi Arabia 41.90–51.20 
Tunisia 31.00 
Belgium 6.00 
Czechia 26.46 
Germany 11.32 18.84 22.4 
Netherlands 5.02 
Norway 24.50 
Sweden 13.14–18.17 15.66 
Turkey 7.52–16.30 12.20 
United Kingdom 4.50–60.00 48.81 
India 91.43 
Thailand 12.79–82.19 35.85 
Brazil 17.24 21.00–69.50 33.75 15.84 
Chile 48.80 
Jamaica 53.90 
Mexico 64.00 
North/South America 7.65–51.85 20.50 
USA 5.00–33.99 12.60 2.53–77.66 30.32 13.37–90.49 37.75 
China 5.12–35.84 24.95 22.38 5.85–91.10 49.76 
Japan 10.00–42.23 12.00 
Malaysia 45.00 
Marshall Islands 55.00 
South Korea 34.26–59.18 37.76 
Countries1962–20002001–20102011–2021
prevalence (%)median (%)prevalence (%)median (%)prevalence (%)median (%)
Africa 7.54–83.42 32.16 
Gambia 2.00–84.00 43.00 
Kenya 14.83–90.49 58.56 
Sierra Leone 69.30–90.80 80.05 
South Africa 30.00 6.00–79.87 13.27 12.15–79.1 28.20 
Uganda 5.37–86.36 58.89 
United Arab Emirates 47.10 
Iran 39.37–43.31 41.34 
Saudi Arabia 41.90–51.20 
Tunisia 31.00 
Belgium 6.00 
Czechia 26.46 
Germany 11.32 18.84 22.4 
Netherlands 5.02 
Norway 24.50 
Sweden 13.14–18.17 15.66 
Turkey 7.52–16.30 12.20 
United Kingdom 4.50–60.00 48.81 
India 91.43 
Thailand 12.79–82.19 35.85 
Brazil 17.24 21.00–69.50 33.75 15.84 
Chile 48.80 
Jamaica 53.90 
Mexico 64.00 
North/South America 7.65–51.85 20.50 
USA 5.00–33.99 12.60 2.53–77.66 30.32 13.37–90.49 37.75 
China 5.12–35.84 24.95 22.38 5.85–91.10 49.76 
Japan 10.00–42.23 12.00 
Malaysia 45.00 
Marshall Islands 55.00 
South Korea 34.26–59.18 37.76 
Fig. 3.

Prevalence of preexisting antibodies against HAdVs in different periods. Most of the countries had studies only in one period, and only four countries (Brazil, China, South Africa, and the USA) had studies published in all three periods.

Fig. 3.

Prevalence of preexisting antibodies against HAdVs in different periods. Most of the countries had studies only in one period, and only four countries (Brazil, China, South Africa, and the USA) had studies published in all three periods.

Close modal

Prevalence of HAdVs Antibodies among Children in Countries

A total of 27 studies have examined the prevalence of antibodies against HAdVs in children. Table 3 reveals that the prevalence rates were ascending order as follows: Europe, Africa, Western Pacific, the Americas, Eastern Mediterranean, and Southeast Asia. Among all countries, Germany reported the lowest median prevalence of children (4.69%), while India reported the highest (96.87%) [39, 47]. The studies conducted in China had the highest number, with a median prevalence of 24.14% [66, 71, 75, 77, 81, 83, 85]. A study from Czechia reported a prevalence rate of 26.46% for HAdV36 [37]. Another study, which included over 1,000 samples, reported a prevalence rate of 41.43% for HAdV5, but the specific location of the study was not clear [90, 91].

Table 3.

Prevalence of HAdVs antibodies by regions in children

RegionsCountries or areasDevelopmentReports (n)Samples (n)Prevalence (%)Median (%)
African 818 5.37–65.95 13.27 
 South Africa Developing 818 5.37–65.95 13.27 
Eastern Mediterranean 369 43.31–52.89 48.10 
 Iran Developing 127 43.31 
 Saudi Arabia Developing 242 52.89 
Europe 1,969 2.50–27.08 6.89 
 Czechia Developed 1,179 26.46 
 Germany Developed 160 2.50–18.75 4.69 
 Sweden Developed 401 24.44 
 Turkey Developing 229 7.52–27.08 17.30 
Southeast Asia 32 96.87 
 India Developing 32 96.87 
The Americas 1,325 7.00–66.67 24.00 
 Brazil Developing 110 15.84–66.67 41.26 
 Jamaica Developing 311 55.95 
 Mexico Developing 157 73.89 
 USA Developed 747 7.00–41.92 15.32 
Western Pacific 1,248 0.00–77.78 22.99 
 China Developing 1,165 0.00–77.78 24.14 
 Japan Developed 83 12.05 
Unknown 1,555 
 Unknown 73 23.30 
 Unknown 1,482 41.43 
Overall 27 7,316 0.00–96.87 15.58 
RegionsCountries or areasDevelopmentReports (n)Samples (n)Prevalence (%)Median (%)
African 818 5.37–65.95 13.27 
 South Africa Developing 818 5.37–65.95 13.27 
Eastern Mediterranean 369 43.31–52.89 48.10 
 Iran Developing 127 43.31 
 Saudi Arabia Developing 242 52.89 
Europe 1,969 2.50–27.08 6.89 
 Czechia Developed 1,179 26.46 
 Germany Developed 160 2.50–18.75 4.69 
 Sweden Developed 401 24.44 
 Turkey Developing 229 7.52–27.08 17.30 
Southeast Asia 32 96.87 
 India Developing 32 96.87 
The Americas 1,325 7.00–66.67 24.00 
 Brazil Developing 110 15.84–66.67 41.26 
 Jamaica Developing 311 55.95 
 Mexico Developing 157 73.89 
 USA Developed 747 7.00–41.92 15.32 
Western Pacific 1,248 0.00–77.78 22.99 
 China Developing 1,165 0.00–77.78 24.14 
 Japan Developed 83 12.05 
Unknown 1,555 
 Unknown 73 23.30 
 Unknown 1,482 41.43 
Overall 27 7,316 0.00–96.87 15.58 

Figure 4 presented the investigation of 26 types of HAdVs in children from different countries. Most of these types were studied in only one country. Specifically, HAdV13, HAdV15, and HAdV17 were exclusively investigated in Germany, while HAdV40 was studied in Iran [34, 39]. The highest prevalence rate of 96.88% was observed for HAdV5 in India [4]. In China, 9 types were investigated in children, with HAdV41 and HAdV2 showing the highest prevalence rates of 66.50% and 66.29%, respectively [77, 78]. Conversely, HAdV11 had the lowest prevalence rate of 1.31%, followed by HAdV14 at 1.96% [71]. In the USA, the prevalence of HAdV36 was 24.33%, which represented the highest all types investigated, while HAdV27 had the lowest prevalence rate at 7.09% [58, 62]. Similarly, the prevalence of HAdV36 in the four other countries (Turkey, Sweden, Mexico, and Brazil) was no less than 15.00%, with Mexico reporting the highest prevalence of 73.89% [41, 42, 44, 49, 53]. In Germany, children were investigated for 10 HAdV types, and HAdV15, HAdV19, and HAdV22 had the lowest prevalence rates at around 2.50% [39]. In South Africa, seven HAdV types were investigated, with HAdV5 having the highest prevalence of 57.78% and HAdV48 having the lowest prevalence of 6.06% [28, 31].

Fig. 4.

Prevalence of HAdVs antibodies in children by regions. Different color dots presented different HAdVs types; the size of a dot with 4 quarters presented the size of a prevalence value; the gradient blue depths of areas represented the sizes of median prevalence values; the gray area indicated that there was no relevant literature for that region.

Fig. 4.

Prevalence of HAdVs antibodies in children by regions. Different color dots presented different HAdVs types; the size of a dot with 4 quarters presented the size of a prevalence value; the gradient blue depths of areas represented the sizes of median prevalence values; the gray area indicated that there was no relevant literature for that region.

Close modal

Prevalence of HAdVs Antibodies among Adults in Countries

The prevalence of antibodies against HAdVs in adults varied significantly across 27 countries or areas, with a range of 2.00–95.70% (Table 4). The median prevalence rates, in ascending order, were as follows: Europe (17.36%), the Americas (25.07%), Southeast Asia (35.85%), the Eastern Mediterranean (41.90%), Africa (50.48%), and the Western Pacific (55.00%). In Europe, except for the Netherlands and Belgium, the median prevalence in Turkey was lower than the other 4 developed European countries [32, 36, 38‒44, 46]. The median prevalence in developed countries of the Americas and Western Pacific was significantly lower than that in developing countries. Nearly half of the studies (23 out of 47, 48.94%) were conducted in the Western Pacific, with China accounting for the majority of these studies. Among the Chinese studies, 82.61% (19 out of 23) reported a median prevalence of 62.59% (ranging from 5.85% to 95.7%) [30, 65‒74, 76‒79, 81, 83‒85]. There were 10 studies conducted in the USA, with a median prevalence of 13.59% (ranging from 2.53% to 77.66%) [28, 29, 32, 54‒57, 59, 61, 63]. In Africa, Europe, the Americas, and the Western Pacific, the median prevalence among adults was higher than that among children. In contrast, the median prevalence among adults in the Eastern Mediterranean and Southeast Asia was lower than that among children.

Table 4.

Prevalence of HAdVs antibodies by regions in adults

RegionsCountries or areasDevelopmentReports (n)Samples(n)Prevalence (%)Median (%)
African 2,394 2.00–90.80 50.48 
 Africa 199 7.54–83.42 32.16 
 Gambia Developing 50 2.00–84.00 43.00 
 Kenya Developing 263 14.83–90.49 58.56 
 Sierra Leone Developing 498 69.3–90.80 80.05 
 South Africa Developing 1,604 13.09–88.27 32.27 
 Uganda Developing 242 5.37–86.36 58.89 
Eastern Mediterranean 1,180 30.58–47.07 41.90 
 United Arab Emirates Developed 973 47.07 
 Saudi Arabia Developing 86 41.90 
 Tunisia Developing 121 30.58 
European 5,617 6.00–52.38 17.36 
 Belgium Developed 250 6.00 
 Germany Developed 472 10.31–44.38 29.06 
 Netherlands Developed 131 6.10 
 Norway Developed 1,268 24.50 
 Sweden Developed 3,275 13.14–16.58 14.86 
 Turkey Developing 179 12.20–12.31 12.26 
 UK Developed 116 1.35–52.38 45.23 
Southeast Asia 438 12.79–82.19 35.85 
 Thailand Developing 438 12.79–82.19 35.85 
The Americas 12 6,158 2.53–77.66 25.07 
 Brazil Developing 200 44.00–69.50 56.75 
 Chile Developing 250 48.80 
 Jamaica Developing 101 47.52 
 North/South America 405 7.65–51.85 20.50 
 USA Developed 10 5,202 2.53–77.66 13.59 
Western Pacific 23 11,247 5.85–95.70 55.00 
 China Developing 19 9,990 5.85–95.70 62.59 
 Japan Developed 361 20.00–54.14 29.00 
 Malaysia Developing 160 45.00 
 Marshall Islands Developing 93 54.84 
 South Korea Developed 736 34.26–59.18 37.76 
Overall 47 27,034 2.00–95.70 38.11 
RegionsCountries or areasDevelopmentReports (n)Samples(n)Prevalence (%)Median (%)
African 2,394 2.00–90.80 50.48 
 Africa 199 7.54–83.42 32.16 
 Gambia Developing 50 2.00–84.00 43.00 
 Kenya Developing 263 14.83–90.49 58.56 
 Sierra Leone Developing 498 69.3–90.80 80.05 
 South Africa Developing 1,604 13.09–88.27 32.27 
 Uganda Developing 242 5.37–86.36 58.89 
Eastern Mediterranean 1,180 30.58–47.07 41.90 
 United Arab Emirates Developed 973 47.07 
 Saudi Arabia Developing 86 41.90 
 Tunisia Developing 121 30.58 
European 5,617 6.00–52.38 17.36 
 Belgium Developed 250 6.00 
 Germany Developed 472 10.31–44.38 29.06 
 Netherlands Developed 131 6.10 
 Norway Developed 1,268 24.50 
 Sweden Developed 3,275 13.14–16.58 14.86 
 Turkey Developing 179 12.20–12.31 12.26 
 UK Developed 116 1.35–52.38 45.23 
Southeast Asia 438 12.79–82.19 35.85 
 Thailand Developing 438 12.79–82.19 35.85 
The Americas 12 6,158 2.53–77.66 25.07 
 Brazil Developing 200 44.00–69.50 56.75 
 Chile Developing 250 48.80 
 Jamaica Developing 101 47.52 
 North/South America 405 7.65–51.85 20.50 
 USA Developed 10 5,202 2.53–77.66 13.59 
Western Pacific 23 11,247 5.85–95.70 55.00 
 China Developing 19 9,990 5.85–95.70 62.59 
 Japan Developed 361 20.00–54.14 29.00 
 Malaysia Developing 160 45.00 
 Marshall Islands Developing 93 54.84 
 South Korea Developed 736 34.26–59.18 37.76 
Overall 47 27,034 2.00–95.70 38.11 

According to Figure 5, the global prevalence of HAdV5 in adults was only slightly lower than that of other types of HAdVs. In a study conducted in China, 9 types of HAdVs were investigated in adults. The highest prevalence was observed for HAdV41 with a prevalence rate of 95.70%, while the lowest prevalence was found for HAdV55, with a prevalence rate of 5.85% [66, 79]. In Japan, the prevalence of HAdV11 (54.14%) was higher in Japan compared to China (24.00%) [71, 86], and it was the highest among the three types of HAdVs investigated in Japan [87]. HAdV40 had the lowest prevalence in Japan, at 20.00%. In the USA, the prevalence rates of the 4 HAdVs (HAdV5, HAdV4, HAdV36, HAdV7) reported were similar, ranging around 30.00% [29, 54‒56, 61, 63]. In the UK, the prevalence of antibodies against HAdV8 was the lowest, with 1.35% [32], while in Malaysia and the Marshall Islands, it was as high as 45.00% [32].

Fig. 5.

Prevalence of HAdVs antibodies in adults by regions. Different color dots presented different HAdVs types; the size of a dot with 4 quarters presented the size of a prevalence value; the gradient blue depths of areas represented the sizes of median prevalence values; the gray area indicated that there was no relevant literature for that region.

Fig. 5.

Prevalence of HAdVs antibodies in adults by regions. Different color dots presented different HAdVs types; the size of a dot with 4 quarters presented the size of a prevalence value; the gradient blue depths of areas represented the sizes of median prevalence values; the gray area indicated that there was no relevant literature for that region.

Close modal

Prevalence of HAdVs Antibodies among Infants in Countries

A total of 1,600 infants were extracted from 9 countries or areas, with a median prevalence of 13.49% (Table 5). The highest prevalence was observed in India, while the lowest prevalence was found in South Africa [28, 47]. The prevalence rates in three developed countries (Germany, UK, and Japan) varied significantly, with rates of 2.38% for HAdV8, 59.52% for HAdV1, and 8.51% for HAdV40, respectively [39, 46, 87]. Some studies investigated the prevalence of HAdV5 in infants in South Africa, India, and China. The prevalence in South Africa was 13.36%, which was much lower than India (86.84%) and China (82.30%, p < 0.05) [31, 47, 85]. Another study from South Africa reported that only one of 149 infants was seropositive for HAdV26, and none were seropositive for HAdV35 [28]. Studies from China showed a higher prevalence of HAdV3 (33.33%) compared to HAdV7 (20.48%) in infants, while the prevalence of HAdV7 was higher than HAdV4 (p < 0.05) [80, 83]. Studies investigating infants in the UK demonstrated that the prevalence of HAdV3 (45.23%) was lower than HAdV1 (59.52%, p < 0.05) [46].

Table 5.

Prevalence of HAdVs antibodies among infants in countries

RegionsCountries or areasDevelopmentReports (n)Samples (n)Seroprevalence (%)Median (%)
Africa South Africa Developing 366 0.00–13.36 0.67 (0.34, 7.02) 
Eastern Mediterranean Saudi Arabia Developing 47 42.55 
Europe Germany Developed 126 2.38 
 UK Developed 42 59.52 
Southeast Asia Indian Developing 38 86.84 
The Americas Brazil Developing 107 63.55 
 Jamaica Developing 20 15.00 
Western Pacific China Developing 807 19.70–82.30 20.24 (19.91, 30.12) 
 Japan Developed 47 8.51 
Overall   14 1,600 0.00–86.84 13.49 (6.67, 20.00) 
RegionsCountries or areasDevelopmentReports (n)Samples (n)Seroprevalence (%)Median (%)
Africa South Africa Developing 366 0.00–13.36 0.67 (0.34, 7.02) 
Eastern Mediterranean Saudi Arabia Developing 47 42.55 
Europe Germany Developed 126 2.38 
 UK Developed 42 59.52 
Southeast Asia Indian Developing 38 86.84 
The Americas Brazil Developing 107 63.55 
 Jamaica Developing 20 15.00 
Western Pacific China Developing 807 19.70–82.30 20.24 (19.91, 30.12) 
 Japan Developed 47 8.51 
Overall   14 1,600 0.00–86.84 13.49 (6.67, 20.00) 

– indicates only one report.

Prevalence of Antibodies against HAdVs by Gender

A total of 24 articles presented data on prevalence stratified by gender. The prevalence ranged from 4.76 to 92.09% among males and from 6.74 to 93.00% among females (Table 6). Out of the 24 articles, only 6 demonstrated statistically significant differences in prevalence between males and females.

Table 6.

Prevalence of antibodies against HAdVs by gender

PublicationCountryMaleFemalep value
sample (n)prevalence (%)sample (n)prevalence (%)
Wang et al. [30] (2018) China 120 54.20, 69.20 135 46.70, 76.30 0.255 
China 123 64.22, 82.00 137 64.23, 87.60 0.289 
Sierra Leone 268 61.20, 88.80 230 71.70, 93.00 0.141 
Zhou et al. [65] (2018) China 486 52.06 338 46.45 0.130 
Sharon et al. [54] (1998) USA 173 38.70, 29.50 97 27.80, 23.70 0.095 
Vander et al. [91] (2013) 16 12.50 57 26.31 0.404 
Nader et al. [33] (2020) United Arab Emirates 477 41.30 496 52.60 0.001* 
Wang et al. [67] (2014) China 226 69.90, 11.10 165 80.00 0.033* 
Yu et al. [69] (2012) China 665 72.63 585 66.32 0.018* 
Ye et al. [70] (2018) China 704 60.20, 62.90 598 56.2, 64.90 0.156 
Huang et al. [74] (2015) China 203 66.01 201 69.65 0.498 
Rohina et al. [55] (2011) USA 482 12.90 745 13.80 0.741 
Minako et al. [86] (1995) Japan 188 43.62 1,998 40.91 0.663 
Malin et al. [41] (2012) Sweden 219 19.50 215 15.60 0.314 
Isela et al. [53] (2013) Mexico 75 50.80 82 49.10 0.262 
Charles et al. [60] (2010) USA 70 12.86 54 18.52 0.538 
Broderick et al. [61] (2010) USA 205 32.20 88 46.59 0.027* 
Berger et al. [62] (2014) USA 146 39.04 145 44.83 0.378 
Na et al. [89] (2012) South Korea 270 29.63 270 38.89 0.030* 
Aldhoon et al. [37] (2014) Czechia 557 19.75 622 32.48 0.000* 
Sun et al. [77] (2011) China 144 75.00 134 79.85 0.411 
Dieter et al. [39] (1967) Germany 357 12.04, 25.21, 22.69, 22.69, 4.76, 17.65, 16.53, 7.84, 18.77, 6.16, 25.77, 24.37 341 11.14, 29.33, 21.70, 21.41, 6.74, 16.72, 14.96, 8.80, 18.77, 8.21, 23.75, 21.11 0.256 
Malin et al. [42] (2014) Sweden 891 14.93 798 11.15 0.026* 
Li et al. [78] (2017) China 278 92.09 222 92.34 0.916 
Liu et al. [79] (2018) China 279 5.37 46 8.70 0.598 
Zhu et al. [84] (2016) China 229 35.37 132 42.11 0.143 
PublicationCountryMaleFemalep value
sample (n)prevalence (%)sample (n)prevalence (%)
Wang et al. [30] (2018) China 120 54.20, 69.20 135 46.70, 76.30 0.255 
China 123 64.22, 82.00 137 64.23, 87.60 0.289 
Sierra Leone 268 61.20, 88.80 230 71.70, 93.00 0.141 
Zhou et al. [65] (2018) China 486 52.06 338 46.45 0.130 
Sharon et al. [54] (1998) USA 173 38.70, 29.50 97 27.80, 23.70 0.095 
Vander et al. [91] (2013) 16 12.50 57 26.31 0.404 
Nader et al. [33] (2020) United Arab Emirates 477 41.30 496 52.60 0.001* 
Wang et al. [67] (2014) China 226 69.90, 11.10 165 80.00 0.033* 
Yu et al. [69] (2012) China 665 72.63 585 66.32 0.018* 
Ye et al. [70] (2018) China 704 60.20, 62.90 598 56.2, 64.90 0.156 
Huang et al. [74] (2015) China 203 66.01 201 69.65 0.498 
Rohina et al. [55] (2011) USA 482 12.90 745 13.80 0.741 
Minako et al. [86] (1995) Japan 188 43.62 1,998 40.91 0.663 
Malin et al. [41] (2012) Sweden 219 19.50 215 15.60 0.314 
Isela et al. [53] (2013) Mexico 75 50.80 82 49.10 0.262 
Charles et al. [60] (2010) USA 70 12.86 54 18.52 0.538 
Broderick et al. [61] (2010) USA 205 32.20 88 46.59 0.027* 
Berger et al. [62] (2014) USA 146 39.04 145 44.83 0.378 
Na et al. [89] (2012) South Korea 270 29.63 270 38.89 0.030* 
Aldhoon et al. [37] (2014) Czechia 557 19.75 622 32.48 0.000* 
Sun et al. [77] (2011) China 144 75.00 134 79.85 0.411 
Dieter et al. [39] (1967) Germany 357 12.04, 25.21, 22.69, 22.69, 4.76, 17.65, 16.53, 7.84, 18.77, 6.16, 25.77, 24.37 341 11.14, 29.33, 21.70, 21.41, 6.74, 16.72, 14.96, 8.80, 18.77, 8.21, 23.75, 21.11 0.256 
Malin et al. [42] (2014) Sweden 891 14.93 798 11.15 0.026* 
Li et al. [78] (2017) China 278 92.09 222 92.34 0.916 
Liu et al. [79] (2018) China 279 5.37 46 8.70 0.598 
Zhu et al. [84] (2016) China 229 35.37 132 42.11 0.143 

*Means p value less than 0.05.

Prevalence of HAdVs Antibodies in Special Populations

A total of 5 studies examined the prevalence of HAdVs among 1,775 soldiers from 3 countries (the USA, China, and South Korea) [54, 61, 76, 79, 88]. The prevalence ranged from 5.85 to 85.48%. One study conducted in 2010 found that the prevalence of HAdv36 (36.52%) in the USA military was higher than that in the local general population [61]. In the Chinese military, the prevalence of HAdV55 was 5.85%, which was much lower than the result reported in another study from China (22.40%) [73, 79]. In South Korea, a prevalence of 85.48% for HAdV55 in soldiers was reported, significantly higher than the prevalence found in China for the same type [88]. Furthermore, the prevalence of HAdV55 was lower in newly recruited soldiers than veteran, while the opposite was observed for HAdv4 [88].

There were 5 included studies that focused on individuals infected with the human immunodeficiency virus (HIV) or populations at high risk for HIV infection [28, 56, 57, 77, 78]. The prevalence of antibodies against HAdVs among HIV-infected individuals ranged from 11.57% (USA) to 88.70% (China), while for populations at high risk for HIV infection, the prevalence ranged from 7.57 (USA) to 90.49% (Kenya) [28, 57, 78]. Control groups were included in all of these studies, which consisted of individuals without HIV infection or those at low risk for HIV infection. The differences in prevalence between the control groups and experimental groups were statistically significant. Moreover, a significantly higher proportion of individuals in experimental groups exhibited high levels of antibody titers compared to the control groups.

Prevalence of Antibodies against HAdV5

A total of 18 studies conducted in 12 countries or regions reported the prevalence of HAdV5 (Fig. 6). The prevalence of HAdV5 varied from 22.38 to 91.43%, with a median prevalence of 74.20%. Among these countries, Southeast Asia exhibited the highest median prevalence of 86.81% (ranging from 82.19 to 91.43%) [28]. The USA, as the sole developed country included in the studies, reported the lowest median prevalence of HAdV5 at 38.08% [28]. In contrast to the USA, the remaining countries had a median prevalence of HAdV5 above 50% [30, 48, 68].

Fig. 6.

The global distribution of pre-existing antibodies against HAdV5 by regions. The gradient blue depths of areas represented the sizes of median prevalence values; the gray area indicated that there was no relevant literature for that region.

Fig. 6.

The global distribution of pre-existing antibodies against HAdV5 by regions. The gradient blue depths of areas represented the sizes of median prevalence values; the gray area indicated that there was no relevant literature for that region.

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Prevalence of Antibodies against HAdV36

The prevalence of HAdV36 in various populations from 12 countries, comprising a total of 11,433 individuals, was reported. The median prevalence was found to be 25.29%, ranged from 5.02% to 73.89% (Table 7). Among different regions, Europe had the lowest median prevalence of 12.67%, followed by the Americas, Western Pacific, and Eastern Mediterranean. In terms of developed countries, South Korea had the highest prevalence of 34.26%, while the Netherlands and Belgium had the lowest prevalence, both below 6.00% [36, 89]. Furthermore, with the exception of Turkey, almost all developing countries had a higher prevalence of HAdV36 compared to developed countries. Despite being a developing country, Turkey had a higher median prevalence of HAdV36 compared to Belgium and the Netherlands, but lower than all other developed countries [43, 45].

Table 7.

Prevalence of antibodies against HAdV36

RegionsCountries or areasReports (n)Samples (n)Cases (n)Prevalence (%)
Eastern Mediterranean 973 458 47.1 
 Arabia 973 458 47.1 
Europe 5,822 984 5.02–26.46 
 Belgium 250 15 6.00 
 Czechia 1,179 312 26.46 
 Netherlands 259 13 5.02 
 Sweden 3,676 583 13.14–18.17 
 Turkey 458 61 7.52–16.30 
The Americas 3,201 856 13.40–73.89 
 Brazil 101 16 15.84 
 Chile 250 122 48.8 
 Mexico 157 116 73.89 
 USA 2,693 602 13.40–41.92 
Western Pacific 1,364 595 34.26–49.76 
 China 824 410 49.76 
 South Korea 540 185 34.26 
unknown Unknown 73 17 23.3 
Overall 20 11,433 2,910 5.02–73.89 
RegionsCountries or areasReports (n)Samples (n)Cases (n)Prevalence (%)
Eastern Mediterranean 973 458 47.1 
 Arabia 973 458 47.1 
Europe 5,822 984 5.02–26.46 
 Belgium 250 15 6.00 
 Czechia 1,179 312 26.46 
 Netherlands 259 13 5.02 
 Sweden 3,676 583 13.14–18.17 
 Turkey 458 61 7.52–16.30 
The Americas 3,201 856 13.40–73.89 
 Brazil 101 16 15.84 
 Chile 250 122 48.8 
 Mexico 157 116 73.89 
 USA 2,693 602 13.40–41.92 
Western Pacific 1,364 595 34.26–49.76 
 China 824 410 49.76 
 South Korea 540 185 34.26 
unknown Unknown 73 17 23.3 
Overall 20 11,433 2,910 5.02–73.89 

Prevalence of Antibodies against Other Types of HAdVs

HAdV36, HAdV5, and HAdV4 were the most commonly reported types in all studies, with HAdV7, HAdV26, HAdV3, and HAdV55 following closely. HAdV4 was mentioned in studies conducted in China, Sierra Leone, South Korea, and the USA [30, 54, 70, 71, 80, 83, 88]. The prevalence of HAdV4 ranged from 16.00% in China to 69.30% in Sierra Leone (Table 8). HAdV7 was reported in the USA and China, with prevalence ranging from 5.12 to 63.82%. In the 1900s, HAdV7 had a similar prevalence in both countries (30.00%), but a more recent study in China reported a higher prevalence (63.82%) [54, 70, 80]. The prevalence of HAdV26 was investigated in nine countries or areas and ranged from 8.56 to 67.77%. Developed countries still had higher prevalence rates compared to developing countries. In the USA, the prevalence of HAdV26 was less than 25%, while it exceeded 50% in Uganda, Kenya, and Thailand [28, 58]. The prevalence of HAdV3 ranged from 33.33 to 78.00% in China, Jamaica, and the UK [46, 52, 71, 83].

Table 8.

Prevalence of pre-existing antibodies against different types

CountriesHAdV4HAdV7HAdV26HAdV3HAdV55
Brazil 44.00 
China 16.00–58.40 5.12–63.82 35.30 33.33–78.00 2.00–34.00 
Germany 25.93 
Jamaica 53.92 
Kenya 66.16 
North/South America 25.43 
Sierra Leone 79.03 
South Africa 13.74–45.57 
South Korea 59.18 18.06–56.00 
Thailand 54.57 
The UK 45.23 
The USA 33.99 27.39 8.56–15.13 
Uganda 67.77 
CountriesHAdV4HAdV7HAdV26HAdV3HAdV55
Brazil 44.00 
China 16.00–58.40 5.12–63.82 35.30 33.33–78.00 2.00–34.00 
Germany 25.93 
Jamaica 53.92 
Kenya 66.16 
North/South America 25.43 
Sierra Leone 79.03 
South Africa 13.74–45.57 
South Korea 59.18 18.06–56.00 
Thailand 54.57 
The UK 45.23 
The USA 33.99 27.39 8.56–15.13 
Uganda 67.77 

HAdVs have become increasingly popular as vaccine or drug vectors. However, the presence of pre-existing antibodies posed a significant challenge in the prevention of infectious diseases or treatment of cancers. It was inevitable that preexisting antibodies could impact the development of AdV-vector vaccines and drugs. Therefore, types with a lower prevalence of absence of preexisting antibodies within populations might be more favorable choices as vectors for vaccines and drugs.

An example of a vaccine developed for COVID-19, called ChAdOx1 nCoV-19, by the University of Oxford and AstraZeneca, utilized a chimpanzee AdV vector in order to circumvent the issue of preexisting antibodies of HAdVs [17]. Therefore, it is crucial to study the presence of preexisting antibodies prior to the development of AdV-vector vaccines or drugs. This study aimed to summarize the global prevalence of preexisting antibodies against different HAdV types in various areas and populations, based on populations from 1962 to 2020. It was found that the prevalence of HAdVs varied significantly between studies and was influenced by multiple factors. Even within the same study, the prevalence of different virus types varied considerably across different populations [21, 22, 31].

Of the 31 countries or areas that reported prevalence of preexisting antibodies against HAdVs, the regions of Africa and the Western Pacific had the largest range of prevalence. This indicated that the prevalence of different types of HAdVs varied significantly within these regions. A study from Gambia reported the lowest prevalence of HAdV35 but found a high prevalence of up to 80% against HAdV35 within the same population [23]. These findings suggest that the use of HAdV5-vector vaccines may not have the expected effect among individuals in Gambia. The types of HAdVs with low prevalence also varied among populations from different countries. HAdV55 had a low prevalence in Chinese children, similar to HAdV11 and HAdV14 [71]. HAdV15, HAdV19, and HAdV22 had a low prevalence in German children, which differed from children in South Africa where HAdV48 had a low prevalence [28‒32]. The same situation could be observed in adults. Therefore, AdV-vector studies should consider that a vaccine based on one HAdV-type vector might be ineffective for different populations in different regions.

Given the widespread presence of HAdVs in the nature environment and the heightened susceptibility of these viruses, the likelihood of exposure and infection increases with age. In this study, the median infection rate was found to be higher in adults compared to children and higher in children compared to infants. However, in the Southeast Asia region, the median infection rate among adults was found to be lower than among children. It is worth noting that the adult data from Southeast Asia were obtained from the same study, which included a high-risk population for HIV infection [28]. These individuals may have had compromised immune systems, leading to lower antibody production compared to children. This finding should be taken into consideration when interpreting the results.

In April 2022, the UK reported numerous cases of acute hepatitis in children, the cause of which was unknown [92]. Subsequently, more cases were discovered in several countries. The most commonly detected virus in all cases was HAdV41, which showed a greater affinity for the gastrointestinal system and was associated with gastrointestinal symptoms [93, 94]. It was suggested that HAdV infection, possibly in combination with an unidentified additional cofactor, could be a possible cause of acute hepatitis with unknown pathogenicity in children. The authors also noted that the lockdowns implemented during the COVID-19 pandemic may have reduced children’s overall exposure to adenoviruses (including HAdVs), potentially increasing their risk of developing more severe disease if infected post-lockdown [95]. The implementation of lockdown measures resulted in decreased travel, social interaction, and natural exposures, thereby reducing the chances of children being infected with low-dose and low-pathogenicity pathogens, including HAdVs present in the environment. Consequently, children’s immune responses may not have been gradually trained and strengthened against these pathogens. Similar to the previous study [95], it was speculated that some children may have had a dysregulated response to their first HAdV infection. However, this inference remains unverified. Furthermore, it is still unclear whether AdV infection alone or in combination with other unidentified factors led to the development of hepatitis in children. It is challenging to determine whether hepatitis associated with AdVs is a new phenomenon or whether it has previously gone unrecognized [96]. Additionally, the prevalence of preexisting antibodies against HAdV41 in the UK, the first country to report acute hepatitis of unknown etiology in children, remains unknown. Despite HAdV41 being the primary cause of gastrointestinal illness in young children, it has not received sufficient attention. Only three studies assessing the prevalence of preexisting antibodies against HAdV41 were included in this study, and these investigations were conducted in China, Japan, and Iran [34, 66, 87].

The prevalence of HAdVs in adults was found to be higher in developing countries compared to developed countries. HAdVs primarily spread through droplets, fecal-oral routes, and close contact. Developing countries with low economy levels often have poor sanitary conditions, such as crude public toilets and inadequate water supply, which can increase the risk of exposure and infection with various microbes, including HAdVs. Based on research findings, Turkey, as a developing country, has exhibited a lower prevalence of HAdVs in all age groups compared to certain developed countries [43, 44]. The United Nations’ Human Development Report 2022 indicates that Turkey’s Human Development Index (HDI) value has increased by 39.7 percent, from 0.600 to 0.838, between 1990 and 2021 [92]. This increase reflects Turkey’s in developing an advanced healthcare system and emphasizing health promotion. These factors are believed to contribute to the lower prevalence of HAdVs in Turkey.

It was found that the median prevalence of HAdVs antibodies differed significantly between the Western Pacific and the Americas, despite only five countries being included in both regions. The majority of samples in the Western Pacific were from China, a developing country with a relatively high prevalence of HAdVs. Conversely, the majority of samples in the Americas were from the USA, a developed country with a low prevalence of HAdVs.

With the exception of Czechia and Sweden, the prevalence of HAdVs in children from developed countries was found to be lower than that in developing countries. Notably, both studies conducted in Czechia and Sweden focused on examining the prevalence of HAdV36 in relation to obesity [37, 41]. It can be suggested to be the fact that the study populations primarily consisted of overweight or obese children.

The impact of gender on the prevalence of HAdV appeared to be minimal. The majority of the 24 included studies reported no statistically significant difference in the prevalence of antibodies between males and females. This finding aligns with another study which observed a detection rate of 1.78% in males and 1.92% in females admitted to hospitals with respiratory adenoviral infection [93].

This study investigated the prevalence of thirty different types of HAdVs, including HAdV5, HAdV36, HAdV4, HAdV7, and several others. Among them, HAdV5 and HAdV36 were found to be the most commonly studied types. It was observed that the prevalence and titer level of HAdV5 were significantly higher compared to other types. Furthermore, HAdV5 was also identified as the most widely utilized HAdV vector, with many adenoviral vectors currently in development or undergoing clinical trials being modified versions of HAdV5 [28, 29]. However, it is important to note that the higher prevalence of preexisting antibodies in populations could potentially impact the effectiveness of vaccines or drugs that employ HAdV5 as their vectors.

HAdV4 and HAdV7 were identified as the main types responsible for febrile respiratory diseases in the military of USA. The implementation of oral HAdV4 and HAdV7 vaccinations resulted in a decline in the incidence of infection. However, this also led to high antibody levels among military personnel. Among the 64 studies included in this analysis, only one examined the prevalence of HAdV4 and HAdV7 in the USA military in 1998, while another study focused on the prevalence of HAdV36 in the same population [54, 62]. It is essential to investigate of HAdV4 and HAdV7 in the USA military after the introduction of new AdV vaccinations as it could potentially impact the use of other viral vector vaccines within the military.

This study has several limitations. First, the classification of ages into more specific categories was challenging due to variations in age groupings across different studies. As a result, the ages were only grouped into infants, children, and adults for the purpose of this study. Second, although studies from 1962 to 2021 were included, there were certain years where only one or no articles were available. Therefore, when comparing the prevalence across different regions and age groups, the potential impact of the year was not taken into consideration.

This study summarized the prevalence of preexisting antibodies against HAdVs in 31 countries or areas, ranging from 2.00% to 91.43%. Different populations grouped by areas, periods, and ages had varied prevalence of antibodies against different types of HAdVs. The prevalence of HAdVs in developed countries was generally lower than that in developing countries. HAdV5 and HAdV36 had relatively high prevalence, while other types of HAdVs, such as HAdV26 and HAdV55, had low prevalence. Vaccine studies should avoid using HAdV types with high preexisting antibodies in the targeted populations or HAdVs vectors should be modified to minimize the impact of preexisting antibodies. Furthermore, more investigations aimed at diverse populations should be conducted in the future to document the global background levels of preexisting antibodies against HAdVs.

The authors have no conflicts of interest to declare.

This research was supported by “double first-class” construction and scientific research start-up fund of Lanzhou University.

Q.R. revised the manuscript and participated in the conception and design; L.H. and F.J. searched literature, performed the statistical analysis, data visualization, and extracted data; L.H., F.J., W.Y., Z.Q., C.H., and M.M. performed screening of articles; L.H., Z.Q. drafted the manuscript. All the authors approved the final manuscript.

Additional Information

Hui Luo and Qian Zhou contributed equally to this work.

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