Immune responses to a heterologous booster with mRNA based COVID-19 vaccine after priming with an inactivated Newcastle disease virus recombinant vaccine expressing the SARS-CoV-2 spike protein (NDV-HXP-S).

Continuous boosting with the original vaccines based on the Ancestral (Wuhan hu-1) strain to maintain immunity has not been sufficient to detain the emergence and rapid dissemination of viral variants. This study was to evaluate the immune responses and safety of a heterologous boost with bivalent Original/Omicron BA.4-5 vaccine mRNA vaccine given after at least 12 months to those who had been primed with NDV-HXP-S COVID -19 vaccine (an inactivated recombinant Newcastle disease virus vaccine).

Methods: An open-label study assessing the booster effects of the bivalent mRNA vaccine given to those who were primed with two doses of the NDV-HXP-S COVID-19 vaccine (either 3 μg with or without the CpG1018 adjuvant or 10 μg of NDV-HXP-S) at least one year ago. The immune responses were measured accordingly.

Findings: The bivalent mRNA boost was safe. Corresponding geometric mean fold rise (GMFRs) in NT₅₀ against Ancestral strain at D28 were 4.4, 3.3, and 3.6 and further increased to 7.8, 6.6 and 6.3 by D90 in the 3 μg, 3 μg + CpG and 10 μg dose groups, respectively. In contrast, the GMFR NT50 against XBB.1.5 peaked at D28 to 11.8, 11.3 and 8.4 and declined to 3.3, 4.0 and 2.6 at D90 in the three dose groups, respectively. Regarding the IFN-gamma response, the group primed with 3 μg + CpG had a greater T cell response by D90 than the other two groups. There was a trend in higher NT₅₀ against XBB.1.5 after boosting, especially among participants in the hybrid-immune subgroup who had a SARS-CoV-2 infection more than 12 months. No safety concerns reported.

Conclusion: The immune responses stimulated by the heterologous boost with bivalent mRNA vaccine in the NDV-HXP-S primed groups were high especially among the hybrid immune subgroup. Thai Clinical Trial Registry: WHO REGISTRY PLATFORM- TCTR20230809003.