Autor:innen:
S. Chalkias (Cambridge, MA, US)
F. Eder (Endwell, New York, US)
B. Essink (Omaha, Nebraska, US)
S. Khetan (Rockville, Maryland, US)
B. Nestorova (Cambridge, MA, US)
J. Feng (Cambridge, MA, US)
H. Zhou (Cambridge, MA, US)
D. Edwards (Cambridge, MA, US)
D. Montefiori (Durham, North Carolina, US)
R. Pajon (Cambridge, MA, US)
B. Leav (Cambridge, MA, US)
J. Miller (Cambridge, MA, US)
R. Das (Cambridge, MA, US)
A. v. Krempelhuber (München, DE)
Objective
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have raised concerns given their potential to circumvent immunity elicited by natural infection or vaccination. To date, the greatest reduction of neutralizing activity in serum samples from vaccinees has been shown against the beta variant (B.1.351 lineage).
Materials and Methods
mRNA-1273-P205 (NCT04927065) is an ongoing open-label phase 2/3 study evaluating the immunogenicity and safety of variant-matched booster vaccines. mRNA-1273.211 is a multivalent, variant-matched vaccine containing 25 µg of mRNA encoding the ancestral Wuhan-Hu-1 spike protein and 25 µg of mRNA encoding the beta B.1.351 spike protein (total dose 50 µg). mRNA-1273.211 50 µg was administered as a booster dose to ~300 adult participants who had previously received (a median of ~8.7 months earlier) a primary series of 2 doses of mRNA-1273 100 µg in the phase 3 Coronavirus Efficacy (COVE) study; this study demonstrated clinical vaccine efficacy against coronavirus disease 2019 (COVID-19). Pseudovirus neutralizing and spike binding antibodies were measured against ancestral SARS-CoV-2 and its variants by using validated assays.
Results
The geometric mean titers (GMTs) (95% confidence interval [CI]) of pseudovirus neutralizing antibodies (ID50) against the ancestral SARS- CoV-2 were 103 (95% CI, 91-116) before the booster dose and rose 21-fold to 2172 (95% CI, 1952-2416) 28 days after the booster dose. These ancestral-specific post-booster GMTs were higher than the ancestral-specific GMTs 28 days after the primary series of mRNA-1273 in the COVE trial (1132 [95% CI, 1047-1224]; GMT ratio was 1.9 [95% CI, 1.7-2.2]). Beta-specific neutralizing GMTs before the booster dose (26, [95% CI, 23-29]) rose 40-fold 28 days after the booster dose (1032 [95% CI, 913-1168]) and were higher than the beta-specific GMTs 28 days after the primary series (145 [95% CI, 133-158]; GMT ratio was 7.0 [95% CI, 6.1-8.1]). Similar results and a robust antibody response were found in binding antibody assays. Review of the serious adverse event data indicated a similar safety profile between the mRNA-1273.211 booster dose and the booster dose with the mRNA-1273 prototype vaccine.
Summary and Discussion
The multivalent, variant-matched booster vaccine effectively elicited robust antibody responses against both the ancestral SARS-CoV-2 and the beta variant (the most resistant variant to date) in previously immunized individuals with an acceptable safety profile.