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Clinical Trial
. 2024 Aug 16;230(2):e279-e286.
doi: 10.1093/infdis/jiae067.

Interim Report of the Reactogenicity and Immunogenicity of Severe Acute Respiratory Syndrome Coronavirus 2 XBB-Containing Vaccines

Spyros Chalkias  1 , Nichole McGhee  1 , Jordan L Whatley  2 , Brandon Essink  3 , Adam Brosz  4 , Joanne E Tomassini  1 , Bethany Girard  1 , Darin K Edwards  1 , Kai Wu  1 , Arshan Nasir  1 , Diana Lee  1 , Laura E Avena  1 , Jing Feng  1 , Weiping Deng  1 , David C Montefiori  5 , Lindsey R Baden  6 , Jacqueline M Miller  1 , Rituparna Das  1
Affiliations
Clinical Trial

Interim Report of the Reactogenicity and Immunogenicity of Severe Acute Respiratory Syndrome Coronavirus 2 XBB-Containing Vaccines

Spyros Chalkias et al. J Infect Dis. .

Erratum in

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 messenger RNA (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 fifth doses to adults who previously received primary series, third doses of an original mRNA COVID-19 vaccine, and fourth doses of an Omicron BA.4/BA.5 bivalent vaccine. Interim safety and immunogenicity 29 days after vaccination are reported.

Results: Participants (randomized 1:1) received 50-µg of mRNA-1273.815 (n = 50) or mRNA-1273.231 (n = 51); median intervals (interquartile range) from prior BA.4/BA.5 bivalent doses were 8.2 (8.1-8.3) and 8.3 (8.1-8.4) months, respectively. Fold increases in neutralizing antibody (nAb) against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants from prebooster nAb 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, or D614G on day 29. 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 subset (n = 20) 15 days after vaccination. Reactogenicity was similar to that of mRNA-1273 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 update for COVID-19 vaccines.

Keywords: COVID-19; JN.1; Omicron XBB.1.5; SARS-CoV-2 variants; mRNA vaccine.

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Conflict of interest statement

Potential conflicts of interest . S. C., N. M., B. G., D. K. E., K. W., A. N., D. L., L. E. A., J. F., W. D., J. M. M., and R. D. are employees of Moderna and may hold stock/stock options in the company. J. E. T. is a Moderna consultant. D. C. M. reports funding from Moderna for pseudovirus neutralization assays performed in the study. L. R. B. is a co–primary principal investigator of the COVE trial, funded by the National Institute of Allergy and Infectious Diseases and conducted in conjunction with Moderna. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Neutralizing antibodies (nAbs) after a booster dose of XBB.1.5-containing monovalent and bivalent vaccines against XBB.1.5, XBB.1.16, BA.4/BA.5, BQ.1.1, EG.5.1, BA.2.86, and JN.1 variants and ancestral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (D614G). Geometric mean (GM) levels for nAb titers were assessed before the booster (prebooster [PB]) and at days 15 (D15) and 29 (D29) after vaccination for the monovalent (messenger RNA [mRNA]-1273.815) and bivalent (mRNA-1273.231) vaccines using a pseudovirus assay, as described elsewhere [5, 6] and in the Supplementary Methods. Analyses were performed in all participants in the per-protocol set for immunogenicity, regardless of prior SARS-CoV-2 infection, and in those without or with prior infection. Antibody values reported as below the lower limit of quantification (LLOQ; 18.5 [1.3 log10] for ancestral SARS-CoV-2 [D614G] and 36.7 [1.6 log10] for Omicron BA.4/BA.5) are replaced by 0.5 × LLOQ. Values above the upper limit of quantification (ULOQ; 45 118 [4.7 log10] for ancestral SARS-CoV-2 [D614G] and 13 705 [4.1 log10] for Omicron BA.4/BA.5) are replaced by the ULOQ if actual values are not available. Antibody values reported as below the lower limit of detection (LOD; 10 for XBB.1.5, XBB.1.16, BQ.1.1, EG.5.1, BA.2.86, and JN.1) are replaced by 0.5 × LOD. Abbreviations: GMFR, GM fold rise at D15 and D29 relative to PB levels; ID50, median infective dose; NA, not available (D15 data for EG.5, BA.2.86, and JN.1).
Figure 2.
Figure 2.
Solicited local and systemic adverse reactions. Shown are the percentages of participants in whom solicited local or systemic adverse reactions occurred within 7 days after the messenger RNA (mRNA) booster dose in the solicited safety set (n = 50 in the monovalent XBB.1.5 vaccine group and n = 51 in the bivalent XBB.1.5 vaccine group).
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References

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