The COVID-19 pandemic, caused by SARS-CoV-2, necessitated the rapid development and deployment of vaccines. Among these, mRNA vaccines, such as the BNT162b2 vaccine (Pfizer-BioNTech), have shown high efficacy. These vaccines primarily induce neutralizing antibodies targeting the spike protein (S), crucial for viral entry into host cells. The emergence of new SARS-CoV-2 variants, particularly B.1.1.7 and B.1.351, raised concerns about reduced vaccine effectiveness due to mutations in the spike protein affecting antibody binding and neutralization. This study aimed to characterize the neutralizing antibody responses elicited by the BNT162b2 vaccine against these variants of concern, comparing them to responses in individuals who recovered from COVID-19. Understanding the breadth and magnitude of vaccine-induced immunity against emerging variants is essential for informing public health strategies and vaccine development.

Existing literature demonstrated that SARS-CoV-2 infection induces antibodies against the spike and nucleoprotein, with spike-specific antibodies being neutralizing and associated with protective immunity. Studies of COVID-19 patients and vaccine recipients indicated a correlation between prior infection or vaccination and a decreased risk of reinfection. While the long-term persistence of vaccine-induced antibodies is still under investigation, infection-induced neutralizing antibodies have been detected for at least six months post-infection. Several vaccine candidates, including mRNA vaccines (BNT162b2 and mRNA-1273) and adenoviral vector vaccines (ChAdOx1-S and Janssen), have been authorized for use, all aiming to induce spike protein-specific neutralizing antibodies. Initial studies suggested that these vaccines were effective against early circulating variants, but the emergence of variants like B.1.1.7 and B.1.351 raised concerns about their efficacy. Previous research indicated that while B.1.1.7 was susceptible to vaccine-induced antibodies, the neutralization of B.1.351 was significantly reduced, highlighting the need for further investigation into the vaccine's ability to protect against these newer variants.

This study employed a sequential semi-ample cohort of 180 Finnish healthcare workers who received two doses of the BNT162b2 vaccine with a three-week interval. Serum samples were collected before vaccination (0d), three weeks (3wk) after the first dose, and six weeks (6wk) after the first dose (three weeks after the second dose). Enzyme immunoassays (EIA) were used to measure SARS-CoV-2 S-specific IgG, IgA, and IgM antibody responses. Neutralizing antibody titers against four SARS-CoV-2 variants (D614G, B.1.1.7, B.1.351, and B.1.463) were determined using a microneutralization test (MNT). Serum samples from 50 non-hospitalized recovered COVID-19 patients were included for comparison. The researchers also performed genetic analysis of the SARS-CoV-2 isolates to identify mutations in the spike protein. Sequence analysis and structural modeling were used to visualize the location of the mutations on the spike protein. Statistical analyses were performed to compare antibody responses and neutralization titers between different time points, variants, and demographic groups.

The study revealed that two doses of the BNT162b2 vaccine induced high levels of anti-S IgG antibodies in the vaccinated healthcare workers. The second dose significantly increased neutralizing antibody titers against the D614G and B.1.1.7 variants. While neutralization of the B.1.351 variant was significantly reduced (five-fold lower compared to D614G and B.1.1.7 variants), 92% of the vaccinated individuals still displayed a neutralization titer >20 against this variant. Importantly, the vaccinees' neutralization titers were significantly higher than those observed in convalescent COVID-19 patients. The study also found a correlation between EIA values (anti-S1 IgG and total anti-S1 Ig) and MNT titers, suggesting that EIA could be a useful surrogate marker for assessing COVID-19 immunity. Age and gender showed some influence on antibody responses, with older individuals exhibiting lower responses after the first dose, although this difference was less pronounced after the second dose. Females displayed slightly higher neutralization titers than males after the second dose.

This study demonstrates that the BNT162b2 vaccine effectively induces high levels of neutralizing antibodies against multiple SARS-CoV-2 variants, including those of concern. Although the neutralization of B.1.351 was reduced, a substantial proportion of vaccinees maintained protective levels of neutralizing antibodies. The superior response of the vaccine compared to that observed in naturally infected individuals further underscores the effectiveness of the vaccine. The strong correlation between EIA and MNT data suggests the potential for using EIA as a faster and more accessible method for evaluating vaccine-induced immunity. However, it's important to acknowledge that the reduced neutralization capacity against B.1.351 variant highlights the need for ongoing monitoring and adaptation of vaccination strategies. Further research into the development and persistence of cell-mediated immunity is warranted.

This study confirms the efficacy of the BNT162b2 vaccine in inducing robust neutralizing antibody responses against several SARS-CoV-2 variants. While the B.1.351 variant showed reduced susceptibility, a high percentage of vaccinated individuals maintained protective antibody levels. The study highlights the value of EIA as a potential surrogate marker for immune status assessment and the need for ongoing surveillance of vaccine efficacy against emerging variants. Future research should focus on long-term immunity, the role of T-cell responses, and the development of updated vaccines to address variant-specific challenges.

The study's limitations include the relatively small sample size, the focus on a specific geographic region (Finland), and the limited follow-up period for assessing long-term immune responses. The study primarily focuses on humoral immunity and lacks analysis of cell-mediated immunity. The selection of healthcare workers as participants may not fully reflect the response in the broader population. The results may not be generalizable to other vaccines or populations.