OVX033 nucleocapsid vaccine induces cross-reactive T cells and boosts memory in SARS-CoV-2-primed non-human primates

Abstract

SARS-CoV-2 Spike protein evolution compromises sustained efficacy of existing vaccines based on neutralizing antibodies. Here we show that OVX033, a nucleocapsid (NCAP)-based vaccine candidate engineered with the self-assembling oligoDOM™ domain, induces robust cellular immunity in two preclinical models. In hamsters, OVX033 elicits robust systemic and pulmonary IFN-γ T-cell responses, cross-reactive across variants, whereas non-assembled NCAP fails to induce T-cell immunity. In non-human primates, adjuvanted OVX033 triggers NCAP-specific antibodies and polyfunctional CD4 + T cells with Th1/Th17 profiles at both systemic and mucosal sites. A single non-adjuvanted dose of OVX033 recalls potent humoral and Th1 T-cell response in SARS-CoV-2 convalescent macaques. These findings show that OVX033 significantly enhances T-cell immunity compared to the native NCAP and that prior infection reduces the need for repeated dosing and adjuvant use. By targeting a conserved viral antigen, OVX033 supports further clinical evaluation as a complementary T-cell-based vaccine strategy against sarbecoviruses.