Immunogenicity, Safety, and Reactogenicity of Concomitant Administration of the Novavax Vaccine against Omicron XBB.1.5 (NVX-CoV2601) and a 20-valent Pneumococcal Conjugate Vaccine in Adults Aged ≥60 Years: A Randomised, Double-blind, Placebo-controlled, Non-inferiority Trial
Authors: Anselm Jorda, Marlene Prager, Lena Pracher, Patrick Haselwanter, Matthias Jackwerth, Valentin al Jalali, Erdem Yildiz, Amelie Leutzendorff, Maria Weber, Schermin Yourieva, Paula Kammerer, Theresa Pecho, Alice Decaminada, Lena Ederer, Ursula Wiedermann, Lukas Weseslindtner, Monika Redlberger-Fritz, Felix Bergmann, Markus Zeitlinger
Journal: Journal of Infection (2025)

Highlights•Whether combined administration of vaccines can significantly impact immunogenicity and reactogenicity is still debated.•Immunogenicity after co-administration of NVX-CoV2601 with PCV20 was non-inferior to NVX-CoV2601 alone.•Safety and reactogenicity was similar between the NVX-CoV2601-alone group and the combination group.•Our findings suggest that combined vaccination is a viable strategy.AbstractObjectivesThere is conflicting evidence as to whether the combined administration of two vaccines can lead to poorer immunogenicity and reactogenicity. The co-administration of the Omicron-adapted COVID-19 vaccine from Novavax (NVX-CoV2601) and a 20-valent pneumococcal conjugate vaccine (PCV20) has not been previously investigated.MethodsIn this randomised, double-blind, placebo-controlled, non-inferiority trial, immunocompetent participants aged ≥60 years were randomised in a 1:1:1:1 ratio to four groups: NVX-CoV2601 plus PCV20 (combination group); NVX-CoV2601 plus placebo (NVX-only group); PCV20 plus placebo (PCV20-only group); or placebo plus placebo (placebo group). The primary outcome was Omicron-specific anti-spike protein IgG ELISA units at day 28 in the combination group compared with the NVX-only group. Non-inferiority was established if the lower limit of the two-sided 95% CI of the geometric mean titre ratio was above the non-inferiority margin of 0.67. Secondary outcomes included anti-pneumococcal capsular polysaccharide (PCP) IgG ELISA units. Solicited local and systemic adverse events were collected for 7 days after vaccination. This study was registered with ClinicalTrials.gov, number NCT05767606, and the EU Clinical Trials Register, EudraCT number 2022-004118-12.ResultsAll 256 randomised participants completed the study. The baseline characteristics were similar in the four groups. Overall, the median age was 64 (IQR 61 to 69) and 105 (41%) of 256 were male. At day 28, the geometric mean anti-spike protein IgG ELISA units were 534U/mL (95% CI 432-660) in the combination group and 556U/mL (95% CI 460-672) in the NVX-only group, resulting in a geometric mean titre ratio of 0.96 (95% CI 0.73-1.27), thereby meeting the criteria for non-inferiority.Anti-PCP IgG ELISA units at day 28 were 507U/mL (95% CI 416-619) in the combination group and 592U/mL (95% CI 485-723) in the PCV20-only group. Local and systemic reactogenicity was similar in the three active treatment groups. No safety concerns or serious adverse events were observed.ConclusionsImmunogenicity following co-administration of NVX-CoV2601 with PCV20 was non-inferior to administration of NVX-CoV2601 alone. Given the similar safety and reactogenicity profile, our findings may help to overcome concerns about concomitant vaccination and pave the way for combination vaccines.FundingNovavax.Graphical abstract