Custom bivalent COVID mRNA enhancers protect against the BA.5 Omicron . variant

In a recent study published in bioRxiv* Prepress server, researchers from the University of Washington School of Medicine, Moderna, Inc, and the US National Institutes of Health tested two vaccines from the SARS-CoV-2 (SARS-CoV-2)-based ribonucleic acid (mRNA) vaccine program.

Stady: SARS-CoV-2 mRNA vaccines increase the breadth of the equation and protect against the BA.5 variant Omicron.. Image Credit: NIAID


A worrying new variant of the SARS-CoV-2 (VOC) Omicron and its sub variants have reduced the efficacy of coronavirus disease 2019 (COVID-19) vaccines that further enhance transmission of SARS-CoV-2. Multiple mutations (more than 30) in the spike (S) protein of the Omicron substrains enabled them to evade neutralization by vaccine-induced antibodies and infection.

To some extent, the mRNA vaccine boosters overcame the loss of vaccine efficacy against Omicron strains. However, researchers continue to work on mRNA vaccines with omicron-identical S proteins. One of these vaccines, mRNA-1273.529 containing S-identical BA.1 omicron, reduced viral burden in the lungs of mice and non-human primates infected with BA.1.

Similarly, a previous study showed that mRNA-1273.211 encoding Wuhan-1 and Beta VOC S proteins caused increased titers of neutralizing antibodies in humans against Beta, Delta and Omicron BA.1 compared to the parental mRNA-1273 vaccine. In general, bivalent vaccines encoding S proteins from the newly emerged SARS-CoV-2 volatile organic compounds can expand immunity induced by the COVID-19 vaccine.

about studying

In this study, researchers evaluated the immunomodulatory capacity and protection provided by two bivalent vaccines approved for use in Europe and the United States that contain two mRNA molecules encoding the Wuhan-Hu1 proteins and BA.1 or BA4/5S proteins.

The previous vaccine formulation, mRNA-1273.214, contained a 1:1 mixture of mRNAs encoding Wuhan-1 and BA.1S; Whereas the latter, mRNA-1273.222, contains a 1:1 mixture of mRNAs encoding Wuhan-1 and BA.4/5. First, the team vaccinated BALB/c mice with a two-dose series of a bivalent vaccine and a monovalent mRNA vaccine. Then, seven months later, they boosted human angiotensin-converting enzyme K18 (hACE2) with a dose of 0.25 mcg of phosphate-buffered saline, mRNA-1273, mRNA-1273.214, or mRNA-1273.222.


The primary vaccination series of all tested vaccines resulted in strong serum antibody binding responses against S2P, S2P.529 and S2P.045 proteins, although mRNA-1273.529 and mRNA-1273.045 vaccine had lower titer against mismatched S antigens. However, bivalent vaccines had exceptional equivalent breadth. They neutralized Omicron BA.1, BA.4/5 and Wuhan-Hu1 pseudoviruses.

The K18-hACE2-boosted mRNA 1273 mice had a moderately elevated titer of antibodies against the SARS-CoV-2 Wuhan-Hu1 strain and the B.1.617.2 variant. However, these mice did not have neutralizing antibodies against Omicron BA.1 and BA.5, similar to those in humans. Conversely, the mRNA-1273.214 and mRNA-1273.222 bivalent vaccine enhancers caused higher responses to neutralizing antibodies against BA.1 and BA.5. In addition, they provided slightly increased protection against infection and inflammation in the lung. Overall, bivalent vaccine enhancers targeting Omicron sub variants showed tremendous benefit compared to the monovalent mRNA-1273.529 vaccine.

The authors did not observe the protective effect of bivalent vaccine and mRNA boosters in the nasal condyles of test animals. A possible explanation may be that other components of immunity (such as T cells) may be involved in upper respiratory tract (URT) immune protection. In fact, URT is also infiltrated by immunoglobulin G.


The current study provided data favoring the introduction of bivalent enhancers based on BA.1 or BA.4/5 in the United States and Europe where both bivalent vaccines confer increased neutralization titers and protection in the lungs against Omicron BA.5.

*Important note

bioRxiv It publishes preliminary scientific reports that have not been peer-reviewed and therefore should not be considered conclusive, guide clinical practice/health-related behaviour, or be treated as established information.

Journal reference:

  • SARS-CoV-2 mRNA vaccines increase the breadth of neutralization and protection from the BA.5 Omicron variant, Suzanne M. Scheaffer, Diana Lee, Bradley Whitener, Baoling Ying, Kai Wu, Hardik Jani, Philippa Martin, Nicholas J. Amato, Laura E. Avena, Daniela Montes-Pereuta, Stephen de Schmidt, Sigi Odell, Archan Nasir, Joe Yu Chuang, Guillaume Stewart-Jones, Richard A. Cobb, Nicole A. Doria Rose, Andrea Carvey, Sida M. Bashir, Larissa B. Thackray, Darin K. Edwards, Michael S. Diamond, bioRxiv pre-print 2022, DOI: the