https://www.sciencedirect.com/science/article/pii/S1198743X22001422

Discussion
The present study adds significant insight into the potential causes of the observed reduction in vaccine effectiveness over time across different populations [3,14,15]. First, we document that in this large cohort of mainly middle-aged and older individuals with a substantial burden of comorbidities, initial peak antibody responses to all vaccine regimens were robust in 95% of vaccinated individuals. Increasing age was associated with lower levels of neutralizing antibodies, but interestingly, this association was not present when we analyzed relative increases in quantitative SARS-CoV-2 IgG levels. Others have also reported an association between age and neutralizing antibody titres after BTN-162b2 vaccination [16]. Elderly individuals are known to have reduced ability to mount robust and sustained responses to new antigens, and age-related decrease in the production of new B cells from their precursors may lead to production of antibodies with lower avidity and affinity [17]. Thus, it may be important to consider both functional and quantitative measures of antibody levels in the evaluation of vaccine response and protection against COVID-19.

The efficacy of the two mRNA vaccines, BNT162b2 and mRNA-1273, against COVID-19 was almost identical in the respective phase 3 trials, but subsequent studies have indicated that total antibody levels and neutralization activity may be higher after two doses of mRNA-1273 compared to BNT162b2. In one report, recipients of the BNT162b2 vaccine had a 27% higher risk of documented SARS-CoV-2 infection and a 70% higher risk of hospitalization for COVID-19 than recipients of the mRNA-1273 vaccine over 24 weeks of follow-up in a period marked by Alpha-variant predominance [14]. The authors also reported a trend towards higher risk of documented infection among BNT162b2 vaccinees than among mRNA-1273 vaccinees over 12 weeks of follow-up in a period marked by Delta-variant predominance [14]. Others have reported higher SARS-CoV-2–binding antibody response after mRNA-1273 vaccination compared to BNT162b2 vaccination [18,19]. In contrast to our study, these two studies did not measure functional or neutralizing antibodies. Indeed, we not only observed higher levels of total Spike and RBD IgG but also higher levels of functional Spike and RBD-ACE2-blocking antibodies in mRNA-1273 compared to BNT162b2 vaccinees. Differences in immunogenicity and effectiveness between the BNT162b2 and mRNA-1273 vaccines could be due to several factors, including variation in mRNA content of the vaccines (100 vs. 30 μg for mRNA-1273 vs. BNT162b2), differences in the recommended interval between the first and second dose (4 weeks for mRNA-1273 vs. 3 weeks for BNT162b2), or other factors, such as the lipid composition of the nanoparticles used for packaging the mRNA content [8,9,20].

Our study also had some limitations. Due to the temporal variations in the availability of specific COVID-19 vaccines in Denmark, most of the individuals who were categorized as high risk in the national vaccination program received BTN162b2. This may bias the antibody responses in the BTN162b2 to be lower compared to the other groups. Also, the ChAdOx1/mRNA group mainly consisted of female health-care workers, and the timing of their second vaccine was closer to the 3- and 6-month visit. We have used different strategies to balance out the inherent differences between vaccine groups, such as stratification and multivariate adjustment in the analyses, but some residual confounding may persist; therefore, direct comparison of vaccine responses between the groups should be made with caution.

Although we report on plasma levels of SARS-CoV-2 Spike and RBD antibodies, which have been shown to correlate with protection against COVID-19, data on cellular immunity were not available for this study. It should be noted that T-cell responses may be of particular importance in preventing severe COVID-19 among those who become infected with SARS-CoV-2 [13,21].