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Hum Vaccin Immunother . NVX-CoV2372, monovalent mRNA and bivalent mRNA vaccines elicit broadly cross-reactive antibodies against emerging SARS-CoV-

tetano

Editor, Senior Moderator
Hum Vaccin Immunother


. 2026 Dec;22(1):2638022.
doi: 10.1080/21645515.2026.2638022. Epub 2026 May 5.
NVX-CoV2372, monovalent mRNA and bivalent mRNA vaccines elicit broadly cross-reactive antibodies against emerging SARS-CoV-2 variants

Xuan Ying Poh[SUP] 1 2 [/SUP], Shirley Y Y Mah[SUP] 3 [/SUP], Aileen Y Y Yeoh[SUP] 3 [/SUP], Jean-Marc Chavatte[SUP] 4 [/SUP], Daniel R X Lim[SUP] 4 [/SUP], Cheryl C Y Tan[SUP] 4 [/SUP], Hao Ling Tang[SUP] 4 [/SUP], Mihir Gandhi[SUP] 5 6 [/SUP], Nabilah Rahman[SUP] 5 7 [/SUP], Suma Rao[SUP] 8 9 [/SUP], Po Ying Chia[SUP] 8 9 10 [/SUP], Sapna P Sadarangani[SUP] 8 9 11 [/SUP], Yi-Qing Chin[SUP] 2 [/SUP], Lisa F P Ng[SUP] 12 13 [/SUP], Laurent Renia[SUP] 10 13 [/SUP], Raymond T P Lin[SUP] 4 [/SUP], David C Lye[SUP] 8 9 10 12 14 [/SUP], Lin-Fa Wang[SUP] 3 [/SUP], Chee Wah Tan[SUP] 12 [/SUP], Barnaby E Young[SUP] 1 2 8 9 10 [/SUP]


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Free article 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%; p = .027) and NVX-CoV2373 (81.4%; p < .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, p = .010 and bivalent: 0.35, p = .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.

Keywords: COVID-19 vaccine booster; NVX-CoV2373; Omicron subvariants; bivalent mRNA vaccine; immunogenicity.

 
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