Investigating effectiveness of mRNA booster against SARS-CoV-2 Omicron in individuals primed with mRNA or inactivated virus vaccines

Clinical Trials & Research

Scientists have developed vaccines at an unprecedented speed to protect individuals from severe acute respiratory syndromes coronavirus-2 (SARS-CoV-2) infection, which has claimed millions of lives worldwide. The global outbreak of this virus has resulted in the coronavirus disease 2019 (COVID-19) pandemic. 

Study: mRNA booster vaccination enhances antibody responses against SARS-CoV2 Omicron variant in individuals primed with mRNA or inactivated virus vaccines. Image Credit: Michiru13/Shutterstock

Owing to the continual emergence of new variants with increased virulence, transmissibility, and capability to evade immune responses, it is imperative to re-evaluate the efficacy of the available COVID-19 vaccines against these variants. Addressing this need, scientists have determined the effectiveness of different vaccination regimens in eliciting humoral immune responses against the SARS-CoV-2 Omicron variant. They evaluated plasma antibodies and levels of Omicron RBD-specific B cells in individuals who received different priming-booster vaccination regimens. This study has been currently posted to the Research Square* preprint server while under consideration for publication in Scientific Reports.

Background

The emergence of new SARS-CoV-2 variants due to genomic mutations has reduced the efficacy of the available COVID-19 vaccines that are designed based on the spike protein of the original SARS-CoV-2 strain. Scientists have classified the new variants as variants of concern (VOC) and variants of interest (VOI). Several studies have reported a decline in vaccine-induced immune protection over time. To overcome this limitation, the COVID-19 booster vaccination strategy has been formulated. 

In Singapore, the National Vaccine Programme (NVP) has permitted three vaccines, i.e., two mRNA-based vaccines developed by Pfizer-BioNTech/COMIRNATY (BNT162b2) and Moderna (mRNA-1273) and an inactivated virus vaccine developed by Sinovac (CoronaVac), for mass vaccination. NVP introduced booster vaccination in July 2021, by reviewing the available reports about the waning of vaccine-induced protection over time and its efficacy against the new SARS-CoV-2 variants.

In most countries around the world, the Omicron variant has replaced the Delta strain and has become the dominantly circulating SARS-CoV-2 variant. Several studies related to the Omicron variant have reported incidence of breakthrough infection and reduced neutralization capability of antibodies produced via the primary vaccination of different types of vaccine.

About the study

In this study, researchers included healthy donors who were above twenty-one years of age and were recruited under the Singapore Immunology Network study. All the participants received either mRNA (BNT162b2 or mRNA-1273) or an inactivated virus (CoronaVac, BBIBP-CorV) vaccine as their third dose booster.

Researchers obtained peripheral blood before and 28 (±5) days after the booster vaccination. The study cohort contained sixty-six participants including twenty-nine males and thirty-seven females. The participants were categorized into four different groups as follows: 

(a) Homologous mRNA vaccine booster: individuals vaccinated with two doses of mRNA vaccines and mRNA booster vaccine.

(b) Homologous inactivated virus vaccine booster: individuals vaccinated with two doses of inactivated virus vaccines and an inactivated virus vaccine booster.

(c) Heterologous inactivated virus vaccine booster: individuals vaccinated with two doses of mRNA vaccines and an inactivated virus vaccine booster.

(d) Heterologous mRNA vaccine booster: individuals vaccinated with two doses of inactivated virus vaccines and an mRNA vaccine booster.

Findings

Scientists determined the levels of neutralizing antibodies against the Omicron variant and evaluated the frequencies of Omicron RBD-binding B cells in all four study groups. Consistent with previous reports, the current study observed that plasma from participants who received homologous mRNA booster vaccination comprised antibodies with a higher capacity to neutralize the SARS-CoV-2 Omicron variant. 

The current study reported that individuals who received an mRNA booster after two doses of inactivated virus vaccines exhibited higher neutralization of 77.85% against Omicron RBD. This finding is in line with previous studies which revealed individuals who received an mRNA booster following a two-dose regimen of inactivated virus vaccine exhibited a greater neutralizing ability against the Delta and Omicron variants.

Participants who were vaccinated with inactivated virus vaccine booster following two doses of homologous inactivated virus vaccines showed reduced neutralizing capability against the Omicron variant, but a higher neutralizing ability was found against the SARS-CoV-2 original strain or Delta variant.  

The authors reported that a robust enhancement in the median Omicron RBD-specific IgG1 levels (17-19-fold) occurred after a month, in participants who received an mRNA booster vaccine after two doses of either mRNA or inactivated virus vaccine. Thereby, both the groups of participants were found to be protected against the Omicron variant Interestingly, this study reported that individuals who were primed with two doses of mRNA vaccines and boosted with inactivated virus vaccine, exhibited reduced neutralizing capacity against the Omicron variant.

Conclusion

A key strength of this study is the comparison of different vaccination regimens in a single population. However, one of the limitations is that the authors did not estimate antiviral immunity mediated by T cells and other immune cells. Additionally, the durability of humoral responses against the SARS-CoV-2 variant in all the study groups must be studied in the future. Researchers stated that this study would help policymakers to make better public health policies regarding COVID-19 booster vaccination based on the effectiveness of each booster regimen, against Omicron.

*Important notice

Research Square 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.

Journal reference:

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