Booster dose of BNT162b2 after two doses of CoronaVac improves neutralization of SARS-CoV-2 Omicron variant

The emergence of the SARS-CoV-2 Omicron variant, characterized by numerous mutations, raised concerns about vaccine escape, particularly regarding neutralization by antibodies induced by vaccination. Brazil, with a high number of COVID-19 cases and deaths, implemented a widespread vaccination program utilizing CoronaVac. However, with the introduction of variants like Delta and Omicron, a booster dose of the BNT162b2 mRNA vaccine was adopted to enhance protection. This study investigates the effectiveness of a BNT162b2 booster dose following a two-dose CoronaVac regimen in inducing neutralizing antibodies against the Omicron variant in a Brazilian healthcare worker cohort. The research question focuses on determining if this heterologous booster improves the humoral immune response and enhances neutralization antibody titers against Omicron compared to the primary CoronaVac vaccination alone. The study's importance lies in providing valuable data on the efficacy of combination vaccination strategies in combating emerging SARS-CoV-2 variants and informing public health vaccination policies.

Existing literature highlights the challenges posed by SARS-CoV-2 variants, especially Omicron, in evading vaccine-induced immunity. Studies have investigated various vaccine combinations to improve the immune response against these variants. Previous research has indicated that heterologous boosting, using different vaccine platforms, may be beneficial in enhancing neutralizing antibody production and broader immune protection. This study builds upon these findings by specifically evaluating the combination of CoronaVac and BNT162b2 against the Omicron variant, focusing on a large sample size of Brazilian healthcare workers, a particularly vulnerable population.

Ninety healthcare workers who received the two-dose CoronaVac protocol were enrolled. Serum samples were collected at three time points: 30 days (D30) and 60 days (D60) after the second CoronaVac dose, and 30 days (D270) after receiving the BNT162b2 booster dose. A viral microneutralization assay (VNT50) was used to determine the neutralizing antibody titers against the SARS-CoV-2 Omicron variant (HIAE-W.A.) in each sample. Serum samples were heat-inactivated and serially diluted before incubation with the virus. Vero cells were used to assess viral cytopathic effects. The neutralization capacity was determined by the reciprocal dilution at which 50% of cytopathic effects were avoided (VNT50), calculated using the Spearman-Karber algorithm. Statistical analysis was performed using one-way ANOVA and Tukey’s multiple comparisons test. Ethical approval and informed consent were obtained.

The study revealed a significant improvement in neutralizing antibody levels after the BNT162b2 booster dose. At D30, only 16.6% of participants showed detectable neutralizing antibodies, decreasing to 10% by D60. However, this increased dramatically to 76.6% at D270 (post-booster). The mean VNT50 increased by 575.5 times compared to D60 and 43.1 times compared to D30, demonstrating a substantial boost in neutralization capacity against the Omicron variant. The findings highlight the superior effectiveness of heterologous boosting with BNT162b2 in enhancing humoral immunity against Omicron compared to the two-dose CoronaVac regimen.

The findings demonstrate the significant improvement in neutralizing antibody response against the Omicron variant achieved by administering a BNT162b2 booster dose following CoronaVac primary vaccination. This is consistent with other studies indicating the advantages of heterologous boosting strategies in improving immune responses. The observed increase in neutralizing antibodies can be attributed to the conserved regions within the SARS-CoV-2 spike protein, which might facilitate antibody recognition despite the numerous Omicron mutations. The high seroconversion rate observed after boosting emphasizes the practical implications for public health interventions aimed at optimizing protection against emerging variants. The results reinforce the importance of heterologous booster strategies, especially in scenarios where primary vaccination with inactivated vaccines may lead to insufficient neutralizing antibody responses against new variants.

This study provides compelling evidence that a BNT162b2 booster dose significantly enhances the neutralizing antibody response against the SARS-CoV-2 Omicron variant in individuals previously vaccinated with CoronaVac. The substantial increase in seroconversion rates and neutralization titers highlights the benefit of heterologous boosting strategies in overcoming the limitations of inactivated vaccines against emerging variants. Future research could investigate the duration of protection afforded by this combined regimen and explore the efficacy of other heterologous booster combinations.

The study's relatively small sample size and focus on healthcare workers, while allowing for a focused analysis of this important population, might limit the generalizability of the findings to the broader population. Further research is needed to investigate the longer-term effects of the combined vaccination strategy and its efficacy in other demographic groups. The study focuses on serological responses; a more comprehensive evaluation involving cellular immune responses would provide a more complete picture.