Assessing the effects of booster vaccinations against SARS-CoV-2 Omicron variant

In a recent study posted to the bioRxiv* preprint server, researchers analyzed the effect of vaccine booster doses against the severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) Omicron variant.

With the emergence of the most mutated SARS-CoV-2 variant of concern (VOCs), Omicron, the coronavirus disease 2019 (COVID-19) pandemic situation worsened significantly.

With over 30 mutations, the Omicron or B.1.1.529 variant has quickly overtook all of the existing SARS-CoV-2 variants in circulation and is now responsible for most COVID-19 cases globally.

Most of its mutations are within the receptor-binding domain or RBD of the spike (S) protein, which is the key target of neutralizing antibodies elicited by infection or vaccination, raising concerns about the efficiency of existing vaccines based on the original wildtype (WT) SARS-CoV-2.

Several reinfections and vaccine-breakthrough cases were observed for the Omicron variant prompting the administration of booster vaccine doses.  Many types of vaccines are used against SARS-CoV-2 such as the whole virus-inactivated, messenger ribonucleic acid (mRNA)-based, recombinant protein subunit, and Adenovirus-vectored vaccines. The efficacy of booster doses of all these vaccines was analyzed in this study.

The study

In the present study, researchers investigated the immune responses to COVID-19 vaccine boosters in China. The effects of four different vaccines: two-dose CoronaVac (inactivated vaccine or IAV), two-dose BBIBP-CorV (IAV), three-dose ZF2001 (recombinant protein subunit vaccine or PRV), and single-dose Convidecia (Adenovirus-vectored or AdV) were assessed.

The binding, blocking, and neutralizing titers were measured against the Omicron variant in convalescent and fully vaccinated individuals and were compared with the prototype or WT SARS-CoV-2. The immune responses elicited by a booster dose were measured against a control group that did not receive booster vaccines.

Findings

The authors first examined the sensitivity of the Omicron variant to the immune responses elicited by natural infection or a full-course vaccination. The binding antibody titer was found to be 5-10-fold reduced for the B.1.1.529 variant when compared with the WT SARS-CoV-2. Similarly, neutralizing activity against the Omicron variant was lost for all except one specimen (PRV-vaccinated), but nearly all the specimens demonstrated neutralization against the WT SARS-CoV-2. Neutralization assays revealed a several-fold reduction in NT₅₀ titers for the Omicron variant than prototype SARS-CoV-2. Notably, the PRV recipients had the highest neutralizing titers against B.1.1.529 variant but this was one-fifth of that observed for convalescent serum samples. 

The effect of a homologous or heterologous vaccine booster was assessed in IAV recipients. The binding, blocking, and neutralizing activities showed an increase following either homologous or heterologous booster as compared with the control group; however, the researchers noted that AdV booster dose significantly elevated NT₅₀ titers in IAV recipients.  A similar analysis of booster doses on AdV-vaccinated individuals was conducted that demonstrated increased binding, blocking, and neutralizing activities. Notably, the heterologous PRV booster showed a higher NT₅₀ titer in AdV recipients.

Based on the observation that a heterologous booster dose enhanced neutralizing titers relatively more than the homologous dose, the authors speculated that a variant-specific vaccine could achieve better results. To test this, the team developed mRNA-based WT, Beta-, Delta- and Omicron–specific booster vaccine shots that were injected after the administration of a single vaccine based on the WT SARS-CoV-2. The authors observed that mice injected with Delta- and Omicron-specific mRNA boosters had higher neutralizing activities against the B.1.1.529 variant and the Omicron-specific vaccine significantly increased the NT₅₀ titers against the Omicron variant compared to any other type of booster.

Conclusions

Overall, the study results showed that fully vaccinated individuals lacked Omicron-specific neutralization despite demonstrating neutralizing activity against the WT SARS-CoV-2. The neutralization potency of fully vaccinated IAV and AdV recipients was < 1/20 of that observed in the sera from convalescent individuals. The findings showed that booster doses, especially a heterologous vaccine booster, elicited increased humoral activity, therefore, humoral responses were considerably boosted in IAV and AdV recipients following AdV and PRV booster doses, respectively.

Studies conducted in mice reported that a vaccine booster enhanced humoral response, but it is the variant-specific vaccine booster that significantly increased the antibody neutralizing titers when compared to WT-based booster doses. To conclude, the present study could inform health regulatory bodies and the research community to optimize the booster vaccination policies to efficiently counter the ongoing COVID-19-induced health crisis.

*Important notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information

Written by

Tarun Sai Lomte

Tarun is a writer based in Hyderabad, India. He has a Master’s degree in Biotechnology from the University of Hyderabad and is enthusiastic about scientific research. He enjoys reading research papers and literature reviews and is passionate about writing.