In a recent study posted to the medRxiv preprint* server, researchers in the United States evaluated the immunogenicity and safety of messenger ribonucleic acid (mRNA) vaccines based on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron XBB.1.5.
SARS-CoV-2 Omicron XBB sub-variants exhibit the potential to evade vaccine- or infection-induced immunity. As such, the United States (US) Food and Drug Administration (FDA) has recommended switching to vaccines based on SARS-CoV-2 XBB.1.5 from Fall 2023. mRNA-1273.815 is a monovalent vaccine encoding the SARS-CoV-2 Omicron XBB.1.5/XBB.1.9.1 spike protein. On the other hand, mRNA-1273.231 is a bivalent vaccine encoding BA.4/5 and XBB.1.5/XBB.1.9.1 spike proteins.
Study: Safety and Immunogenicity of XBB.1.5-Containing mRNA Vaccines. Image Credit: Dmitry Kovalchuk / Shutterstock
*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
About the study
In the present study, researchers presented interim immunogenicity and safety data of the mRNA-1273.231 and mRNA-1273.815 vaccines from an ongoing phase 2/3 trial. The vaccine was intramuscularly administered as the fifth dose to recipients of the two-dose primary vaccination series, booster of the original coronavirus disease 2019 (COVID-19) vaccine, and bivalent booster. Individuals were excluded if they had a history of COVID-19 within three months before screening.
The researchers randomized individuals to receive a single monovalent or bivalent booster dose. Formal statistical testing for comparing immunogenicity between groups was not performed. The exploratory endpoint, surveillance of COVID-19 events, did not apply to this 15-day interim analysis. The study’s primary objectives were the reactogenicity, immunogenicity, and safety of the mRNA-1273.231 and mRNA-1273.815 vaccines.
Immunogenicity was evaluated based on neutralizing antibodies (nAbs) against vaccine variants. Safety assessments included unsolicited adverse events (AEs) within 28 days and solicited systemic and local AEs within seven days. The team also evaluated serious or medically-attended AEs, special interest AEs, and those resulting in discontinuation from participation. The team used lentiviral pseudovirus neutralization tests to assess immunogenicity 15 days post-administration.
In addition, a research-grade vesicular-stomatitis virus-based pseudovirus neutralizing test was separately performed for ancestral SARS-CoV-2, FL.1.5.1, EG.5.1, XBB.2.3.2, XBB.1.16, XBB.1.5, and BA.4/5 variants, in a sub-sample of 20 randomly selected recipients of mRNA-1273.815. The team reported geometric mean titers (GMTs) and geometric mean fold-rises (GMFRs) from baseline (pre-booster) levels.
Findings
The researchers randomized 51 and 50 adults to receive mRNA-1273.231 and mRNA-1273.815 vaccines, respectively, in April 2023. Participants generally had similar baseline characteristics. The median time from the last dose was 8.1 and 8.2 months for mRNA-1273.231 and mRNA-1273.815 recipients, respectively.
Both vaccines increased nAb responses against ancestral SARS-CoV-2, BA.4/5, BQ.1.1, XBB.1.5, and XBB.1.16 variants at day 15 relative to pre-booster levels. GMTs and GMFRs were higher against ancestral SARS-CoV-2, XBB.1.5, and XBB.1.16 with the monovalent vaccine than with the bivalent dose but were comparable against BQ.1.1 and BA.4/5 for both vaccines.
The monovalent vaccine induced similar responses against FL.1.5.1, EG.5.1, XBB.2.3.2, XBB.1.5, and XBB.1.16 in the sub-sample tested using the research-grade neutralizing assay. The median follow-up was 20 days for both groups. The unsolicited AEs and solicited systemic and local AEs were similar to previously reported AEs for the mRNA-1273 vaccine or the bivalent BA.4/5-containing mRNA vaccine. Fatal or severe AEs were not observed.
Conclusions
In summary, the tolerability of mRNA-1273.231 and mRNA-1273.815 vaccines was similar to previous vaccines. Both vaccines induced potent nAb responses against sub-variants of the XBB-sublineage. The monovalent dose induced higher nAb titers than the bivalent vaccine. In general, responses were higher against variants of the XBB lineage.
The monovalent vaccine was also effective against the more recent Fornax (FL.1.5.1) and Eris (EG.5.1) variants, which harbor an additional substitution and may evade prior immunity. Overall, the findings reassure the potential of XBB.1.5-based vaccines to protect from emerging variants and support updating to an XBB.1.5-containing monovalent vaccine in 2023-24.
*Important notice: medRxiv 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.
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