NVX-CoV2372, monovalent mRNA and bivalent mRNA vaccines elicit broadly cross-reactive antibodies against emerging SARS-CoV-2 variants.
Bivalent mRNA vaccines showed the highest neutralization levels against the KP.2 subvariant shortly after the booster, but all vaccine types had similar neutralization levels by 12 months.
Where it sits
this study against the rest of the kisspeptin (kp-10) corpusSummary and findings
The study evaluated the immunogenicity of monovalent mRNA, bivalent mRNA, and NVX-CoV2373 vaccines in 176 triple mRNA-vaccinated adults. A fourth vaccine dose significantly boosted neutralizing antibody levels against the Omicron subvariant XBB.1.16 at day 28. Bivalent mRNA vaccines exhibited the highest neutralization level against the KP.2 subvariant.
Abstract
Randomized clinical trials comparing the breadth and long-term persistence of immunity between different COVID-19 vaccine types and between ancestral and Omicron-targeted vaccines are limited. The PRIBIVAC study (Phase D) is a randomized clinical trial comparing the immunogenicity of monovalent mRNA vs bivalent mRNA vs protein-based NVX-CoV2373 administered as second booster in 176 triple mRNA-vaccinated adults. Primary objective was neutralizing antibody levels against Omicron subvariants at day 28. A 4th vaccine dose significantly boosted 50% neutralization titers against emerging strain XBB.1.16 by 3.2-, 4.1- and 1.6-fold in monovalent mRNA, bivalent mRNA and NVX-CoV2373 group respectively at day 28. The largest absolute increase in inhibition level at day 28 post-booster was observed against the KP.2 subvariant, with bivalent mRNA vaccines exhibiting the highest neutralization level (91.7%) compared with monovalent mRNA (84.4%; <i>p</i> = .027) and NVX-CoV2373 (81.4%; <i>p</i> < .0001). While bivalent mRNA vaccines elicited the highest early immunogenicity, neutralization levels against all Omicron variants tested waned to similar levels between groups by 12 months post-vaccination. Although NVX-CoV2373 induced a lower peak anti-S antibody response, anti-S decay rate was slower in NVX-CoV2373 compared with mRNA vaccines. The geometric mean anti-S fold change (D360/D28) in NVX-CoV2373 group was higher (0.51) relative to both mRNA vaccines (monovalent: 0.31, <i>p</i> = .010 and bivalent: 0.35, <i>p</i> = .017). Improved neutralizing antibody responses against diverse SARS-CoV-2 variants by the ancestral or variant vaccine highlight the immunological benefits of COVID-19 vaccine boosters regardless of the latest variant-based vaccine. Further studies to determine if different vaccine combinations translate to differing protection against infection remain necessary.
Background
This paper addresses the comparative immunogenicity of different COVID-19 vaccine types, specifically focusing on the breadth and persistence of immunity against emerging variants. Prior studies have shown varying effectiveness of vaccines against SARS-CoV-2 variants, but direct comparisons between monovalent and bivalent mRNA vaccines have been limited. Understanding these differences is crucial for informing vaccination strategies as variants continue to emerge.
Methods
The PRIBIVAC study was a randomized clinical trial involving 176 triple mRNA-vaccinated adults. Participants received either a monovalent mRNA, bivalent mRNA, or protein-based NVX-CoV2373 vaccine as a second booster. The primary outcome measure was the level of neutralizing antibodies against Omicron subvariants at day 28 post-booster.
Results
At day 28, the bivalent mRNA vaccine group showed a neutralization level of 91.7% against the KP.2 subvariant, significantly higher than the monovalent mRNA at 84.4% (p = .027) and NVX-CoV2373 at 81.4% (p < .0001). Neutralization titers against strain XBB.1.16 were boosted by 4.1-fold in the bivalent mRNA group. The geometric mean anti-S fold change in the NVX-CoV2373 group was 0.51, compared to 0.31 in the monovalent and 0.35 in the bivalent groups (p = .010 and p = .017, respectively).
Interpretation
The study indicates that while bivalent mRNA vaccines elicit a higher initial immune response, the long-term neutralization levels against Omicron variants tend to converge across vaccine types by 12 months. The effect sizes, while statistically significant, may not be clinically meaningful in terms of long-term protection. Limitations include the short follow-up period and potential confounding factors related to the immune response variability among individuals.
Key findings
- 50% neutralization titers against strain XBB.1.16 boosted by 3.2-fold in monovalent mRNA, 4.1-fold in bivalent mRNA, and 1.6-fold in NVX-CoV2373 at day 28.
- Bivalent mRNA vaccines neutralized KP.2 subvariant at 91.7% compared to monovalent mRNA at 84.4% (p = .027) and NVX-CoV2373 at 81.4% (p < .0001).
- Geometric mean anti-S fold change (D360/D28) was 0.51 in NVX-CoV2373 group, compared to 0.31 in monovalent (p = .010) and 0.35 in bivalent (p = .017).
Limitations
- 12-month follow-up may not capture long-term immunity.
- Small sample size of n=176.
- Potential confounding factors related to vaccine type and immune response variability.