Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which is responsible for the COVID-19 pandemic, has affected hundreds of millions of people and caused millions of deaths worldwide [1][2]. As of August 13, 2024, Africa reported 874,036 confirmed cases and 18,498 deaths [3]. In Senegal, there were 89,053 infections and 1971 deaths [2]. To curb the spread of the virus, various measures were implemented globally, including physical distancing, masks-wearing, and the use of protective eyewear [4][5]. These measures effectively reduced exposure risk and subsequently lowered the rate of new infections [6][7]. Further reductions in infection rates were achieved with the introduction of vaccines less than a year after the WHO declared the pandemic [8][9].

Various types of vaccines were developed, including inactivated virus vaccines, adenoviral vector vaccines, and messenger RNA (mRNA) vaccines [8]. In Senegal, vaccines such as Pfizer/BioNTech, AstraZeneca, Moderna, Sinopharm, and Johnson & Johnson (J&J) were administered. Regardless of the manufacturer or technology, these vaccines primarily targeted the Spike protein, which is located on the surface of the SARS-CoV-2 envelope. This protein facilitates binding to the cellular receptor ACE2 and subsequent entry into host cells [10][11]. Several studies have demonstrated that antibodies directed against this protein provide some levels of protection against infection [12][13]. Their effectiveness against ancestral strains ranges from 63% to 86%, while protection against severe forms of COVID-19 ranges from 73% to 95% [14]. However, vaccine efficacy can vary between populations due to genetic and environmental factors. Therefore, it is essential to include diverse populations in clinical trials and to assess the impact of geographical variations on immune responses to inform the future use of these vaccines [15][16].

Like many resource-limited countries, Senegal received the majority of its vaccines through the COVAX initiative and bilateral partnerships. The Ministry of Health distributed these vaccines via the Expanded Programme on Immunisation (EPI), without any prior or subsequent evaluation of immunogenicity. In this context, we assessed the antibody response of participants who received Johnson & Johnson and Sinopharm vaccines over a 12-month period. Our aim was to determine the persistence of vaccine-induced humoral responses, evaluate the benefits of additional booster doses for the population, and analyse the impact of socio-demographic factors and community exposure on antibody production and persistence.

This study focused on monitoring the long-term humoral response to SARS-CoV-2 vaccination by periodic measurement of the levels of targeted anti-bodies to spike protein antigens (S1, S2) and nucleocapsid antigen (Np) for 12 months. It also explored the influence of socio-demographic factors and community-level exposure on these immune responses.

The observed associations between socio-demographic factors and antibody profiles reflect the different exposure patterns and specific characteristics of the administered vaccines. Participants received either two doses of an inactivated whole-virus vaccine (Sinopharm) or one dose of an adenoviral vector vaccine (J&J). Sinopharm can induce antibodies against the Spike protein (S1/S2) and the nucleoprotein (NP) due to its whole-virus composition [17], whereas the Johnson & Johnson vaccine only expresses the Spike protein and does not induce anti-NP antibodies [18].

The association between anti-S1 seropositivity and households with more than 16 members confirms the role of overcrowding in facilitating intra-household transmission, whereby close and prolonged contact increases viral circulation [19][20]. Similarly, commercial workers and students are exposed to repeated interpersonal interactions in high-density environments, which may explain the higher S1/S2 positivity observed in these groups [21][22]. In contrast, the higher anti-NP positivity in Koranic school pupils probably reflects natural infection, as NP antibodies are markers of previous viral replication rather than Spike-only vaccination [23].

On Day 0, prior to any injection, several participants already exhibited high levels of antibodies despite no prior vaccination, suggesting previous natural exposure to SARS-CoV-2. This situation is consistent with the epidemiological context in Senegal during 2022-2023, which was marked by widespread viral circulation and a population largely already immunized, either through natural infection or repeated exposure to the virus. Such pre-existing immunity, well documented in high-transmission settings [24], can enhance vaccine-induced responses through a “booster-like” effect [25]. This could explain the rapid and elevated antibody levels observed shortly after vaccination. However, some variability in immune responses was noted, likely influenced by individual factors such as age, sex, and prior exposure. This study helps to address the gap in immunological data on COVID-19 in African populations and highlights the importance of assessing pre-existing immunity prior to vaccination.

The J&J vaccine (Ad26.COV2. S) initially induced a robust humoral response, with significantly high concentrations of anti-S1 and anti-S2 antibodies observed on days 14 and 28 post-vaccination. These results confirm the efficacy of this single-dose vaccine in generating a rapid immune response, as previously reported in several clinical studies [26]. However, this response progressively diminishes over time, with a notable decline in antibody levels at six and nine months. This decline aligns with findings from other cohorts, where the persistence of antibodies after vaccination with Ad26.COV2.S was lower than that observed with mRNA vaccines [27]. The declining levels of antibodies may be explained by the non-replicating nature of the viral vector platforms, which relies solely on the Spike protein and tends to elicit a strong but transient antibody response. The emergence of viral variants and the absence of additional antigens may also contribute to a less durable immune response [28][29]. Nevertheless, the observed decline in antibody levels may reflect the natural course of the immune response [30], as well as the vaccine’s tendency to induce a predominantly cellular immune response and the generation of memory T and B cells rather than sustained antibody production [31]. These findings are in line with the study by Self et al. [32], which reported that anti-Spike and anti-RBD IgG levels were significantly lower in individuals vaccinated with Johnson & Johnson compared to those who received Moderna or Pfizer-BioNTech vaccines. Overall, these results highlight the importance of monitoring the duration of vaccine-induced immunity and adapting immunization strategies accordingly, particularly through the administration of homologous or heterologous booster doses. Our findings support the use of booster doses to maintain long-term antibody protection, particularly in areas with high viral circulation or among at-risk individuals.

The administration of the first dose of the Sinopharm vaccine led to a slight increase in anti-S1 and anti-NP SARS-CoV-2 antibody levels, while a slight decrease was observed in anti-S2 antibody levels. These findings suggest a modest humoral response induced by the initial dose, with a preferential specificity directed toward the S1 subunit of the Spike protein, which contains the receptor-binding domain (RBD) a major target of neutralizing immunity [33]. The increase in anti-NP antibodies can be attributed to the nature of the Sinopharm vaccine (BBIBP-CorV), which is an inactivated whole-virus vaccine containing all structural viral proteins, including the nucleoprotein (NP). This is consistent with the findings of an earlier study [18], and contrasts with mRNA or viral vector vaccines, which solely express the Spike protein. The observed decrease in anti-S2 antibodies may be due to the intrinsically lower immunogenicity of the S2 subunit compared to S1 [34] suggesting that S2 may be less exposed making it a less dominant target for humoral responses. Additionally, this limited response may reflect a transient redistribution of immune resources, awaiting amplification following the second dose. However, contrary to expectations, no significant booster effect was observed following the administration of the second dose of the vaccine. This could be because the first dose may have induced an immune response that approached the maximal level, thereby limiting further enhancement by the second dose, as previously suggested [32][33] or that the second dose was administered too early, or that the antibody measurements were taken before the immune system had completed its full response to the first dose making the increase in antibody levels not yet apparent. This is consistent with an earlier report which highlighted the importance of optimizing the interval between doses [35]. It is also possible that the second dose only targeted enhancing antibody affinity through affinity maturation rather than increase the overall quantity [36][37]. Finally, individual variability must be considered. Factors such as age, sex, general health status, and comorbidities can significantly influence the magnitude and quality of the immune response as previously described [38][39].

Our study revealed a sex-specific dynamic in the immune response induced by vaccination irrespective of the target antibodies as depicted by the higher levels of anti-S1, anti-S2 and anti-Np antibodies in the early phases of the study among men. However, this trend reversed over time: women gradually developed higher antibody titres and demonstrated greater antibody persistence for both vaccines assessed. This pattern remained consistent throughout the follow-up period in agreement with previous reports of women mounting more durable and protective immune response compared to men [40][41]. This enhanced immunity in females was largely attributed to the influence of sex hormones particularly oestrogens and the presence of immunoregulatory genes on the X chromosome [41]-[43]. In contrast, men tend to exhibit a more intense but transient immune response, often accompanied by heightened inflammation. This phenomenon has also been described by Takahashi et al. (2020), who reported sex-based differences in immune responses to SARS-CoV-2, which helped to explain some of the observed disparities in clinical outcomes [44]. Several studies have shown that various immune cells, such as B lymphocytes, express oestrogen receptors that are regulated by circulating oestrogen levels [45][46]. Moreover, oestrogen has been shown to promote immunoglobulin production, while testosterone may exert an inhibitory effect [47].

Moreso, this study revealed that the levels of anti-S1, anti-S2, and anti-NP antibodies vary depending on the type of vaccine administered and the age group. Overall, the J&J vaccine elicited a stronger immune response in younger individuals, particularly those aged 18 to 30 years, throughout the follow-up period which contrasts the stronger immune response elicited by the Sinopharm vaccine among participants between 46 to 70 years of age particularly at the early stages of the study. This observation may be explained by the higher immunological reactivity of younger adults, who generally exhibit better B and T cell functionality with faster and more effective humoral response. This agree with the report that age is a critical determinant of vaccine immunogenicity, with older individuals often showing a diminished response due to immunosenescence [48][49]. Furthermore, the J&J vaccine, being a viral vector-based platform, may stimulate a stronger initial response in younger individuals whose naïve immune systems are more responsive to this type of vaccine as highlighted in the findings from an earlier study on the immunogenicity and efficacy of the Ad26.COV2. S vaccine [50]. Notwithstanding, the lost to follow-up among participants of age above 46 years leading to incomplete data on long-term effect of the Sinopharm vaccine, the earlier response observed agrees with an earlier report from a study which observed higher average antibody titres in individuals aged 45 and above [51]. Conversely, these results contrast with the conclusions of another study which documented a decline in antibody levels with increasing age among Sinopharm vaccine recipients [52][53]. Potential explanation for this observation could be that the presence of pre-existing immune memory, due to prior exposure to related coronaviruses, could enhance the initial response in older subjects. Additionally, external factors such as stress, fatigue, and nutrition which tend to be more stable in older adults, may also play a favourable role in modulating the immune response [42][43]. Nevertheless, further investigations are needed to better understand the actual underlying mechanisms. Notwithstanding, these results underscore the importance of adopting an age-specific approach when evaluating vaccine immunogenicity which may help inform tailored vaccination strategies, particularly regarding booster administration in older populations.

A major strength of this study is the extended follow-up period, combined with multiple data collection points, enabling a detailed assessment of immune response dynamics over time. The immune response was then analysed according to several key variables, including gender, age and vaccine type. This multidimensional approach explored many factors that could influence immunogenicity. The study also assessed the impact of sociodemographic characteristics and exposure at community level, providing valuable insights into individual and contextual determinants of immune response. This study is limited by the small Sinopharm cohort (n = 44) compared with Johnson & Johnson (n = 331), along with uneven distribution of certain variables, particularly age and sex, and gradual loss to follow-up, may have reduced the statistical power of subgroup analyses and contributed to variability in the results. A more thorough assessment of participants’ overall health status and environmental factors would have been necessary to better understand the observed disparities. Additionally, the analysis focused solely on the humoral response, measured by antibody levels, without evaluating the cellular response (T lymphocytes and their subpopulations), which is crucial for comprehensive immunity. Another important limitation is the absence of antibody neutralization assays, which would have provided valuable complementary data to support the conclusions drawn from ELISA results. Another limitation of this study is the absence of baseline PCR and serological testing, which limited the confirmation of prior SARS-CoV-2 infection among participants. Despite these constraints, this study offers significant insights into vaccine-induced immune responses and paves the way for further in-depth research.

This study evaluated the humoral response induced by the Johnson & Johnson and Sinopharm vaccines in Senegalese adults aged 18 and older. The results confirm the immunogenicity of both vaccines, showing a robust antibody response that gradually declines over time, highlighting the importance of booster doses to maintain long-term immunity. Variations were observed according to age, sex, and vaccine type, emphasizing the influence of individual and contextual factors, some of which warrant further investigation. Finally, this study underscores the need to tailor vaccination strategies, protective measures, and serological monitoring to local realities. Prioritizing the most vulnerable groups while reinforcing effective prevention practices is essential.

We wish to express our sincere gratitude to the Institute of Health Research, Epidemiological Surveillance, and Training (IRESSEF) for its institutional support and guidance throughout this study. We warmly thank all the medical and paramedical staff involved in this work for their valuable collaboration, as well as all the participants for their commitment and trust. Our appreciation also goes to our laboratory colleagues for their technical assistance, and to the IRESSEF data management team for their essential support in data handling and analysis.

FBNM, DJW, TND designed the project.

FBNM, ND, DJW, NKK, ALS, NDD, MSG, and JKB, NAL performed the experimental analyses.

BFNM, ND, OD, AM and IDO analysed the data and prepared the figures & tables.

FBNM, ND and IDO wrote and reviewed the manuscript.

DJW, TND, SOM supervised the overall study.

All authors have read and approved the final submitted version of the manuscript.