Interim report of the reactogenicity and immunogenicity of SARS-CoV-2 XBB-containing vaccines

Spyros Chalkias; Nichole McGhee; Jordan L Whatley; Brandon Essink; Adam Brosz; Joanne E Tomassini; Bethany Girard; Darin K Edwards; Kai Wu; Arshan Nasir; Diana Lee; Laura E Avena; Jing Feng; Weiping Deng; David C Montefiori; Lindsey R Baden; Jacqueline M Miller; Rituparna Das

doi:10.1093/infdis/jiae067

Interim report of the reactogenicity and immunogenicity of SARS-CoV-2 XBB-containing vaccines

J Infect Dis. 2024 Feb 13:jiae067. doi: 10.1093/infdis/jiae067. Online ahead of print.

Authors

Spyros Chalkias¹, Nichole McGhee¹, Jordan L Whatley², Brandon Essink³, Adam Brosz⁴, Joanne E Tomassini¹, Bethany Girard¹, Darin K Edwards¹, Kai Wu¹, Arshan Nasir¹, Diana Lee¹, Laura E Avena¹, Jing Feng¹, Weiping Deng¹, David C Montefiori⁵, Lindsey R Baden⁶, Jacqueline M Miller¹, Rituparna Das¹

Affiliations

¹ Moderna, Inc., Cambridge, MA, USA.
² Meridian Clinical Research, Baton Rouge, LA, USA.
³ Meridian Clinical Research, Omaha, NE, USA.
⁴ Meridian Clinical Research, Grand Island, NE, USA.
⁵ Department of Surgery, Duke University Medical Center, Durham, NC, USA.
⁶ Brigham & Women's Hospital, Boston, MA, USA.

PMID: 38349280
DOI: 10.1093/infdis/jiae067

Abstract

Background: Monovalent Omicron XBB.1.5-containing vaccines were approved for Coronavirus disease 2019 (COVID-19) 2023-2024 immunizations.

Methods: This ongoing, open-label, phase 2/3 study evaluated mRNA-1273.815-monovalent (50-µg Omicron XBB.1.5-spike mRNA) and mRNA-1273.231-bivalent (25-µg each Omicron XBB.1.5- and BA.4/BA.5-spike mRNAs))vaccines, administered as 5th doses to adults who previously received a primary series, a 3rd dose of an original mRNA COVID-19 vaccine, and a 4th dose of an Omicron BA.4/BA.5 bivalent vaccine. Interim safety and immunogenicity results 29 days post-vaccination are reported.

Results: Participants (randomized 1:1) received 50-µg mRNA-1273.815(n=50) or mRNA-1273.231(n=51); median (interquartile range) months from the prior BA.4/BA.5-bivalent dose were 8.2 (8.1-8.3) and 8.3 (8.1-8.4), respectively. Neutralizing antibody (nAb) increased from pre-booster levels against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants tested. Day 29 nAb fold-increases from pre-booster levels were numerically higher against XBB.1.5, XBB.1.16, EG.5.1, BA.2.86, and JN.1 than BA.4/BA.5, BQ.1.1 and D614G. The monovalent vaccine also cross-neutralized FL.1.5.1, EG.5.1, BA.2.86, HK.3.1, HV.1 and JN.1 variants in a participant (n=20) subset, 15 days post-vaccination. Reactogenicity was similar to previously reported mRNA-1273 original and bivalent vaccines.

Conclusions: XBB.1.5-containing mRNA-1273 vaccines elicit robust, diverse nAb responses against more recent SARS-CoV-2 variants including JN.1, supporting the XBB.1.5-spike sequence selection for the 2023-2024 COVID-19 vaccine update.

Keywords: BA.2.86; COVID-19; EG.5.1; HK.3.1; HV.1; JN 1; Omicron; SARS-CoV-2 variants; XBB.1.5; immune response; mRNA vaccine; neutralizing antibody.