Single intranasal immunization with attenuated Wuhan-like SARS-CoV-2 provides highly effective cross-protection against Delta and Omicron VOCs

Abstract

Despite the end of the COVID-19 pandemic, the problem of vaccine prevention of this disease appears highly relevant. The emergence and widespread distribution of the Omicron SARS-CoV-2 variant of concern (VOC) and its sublineages has dramatically reduced the efficacy of vaccination with licensed vaccines. The possible approach to solving this problem is to develop a nasal live attenuated vaccine (LAV) capable of activating humoral, mucosal, and cell-mediated immunity, providing a prolonged immune response and cross-protection against different VOCs. The aim of the present study was to determine the immunization efficacy with attenuated cold-adapted Wuhan-like SARS-CoV-2 D-D2 strain against homologous and heterologous challenges. Single intranasal immunization of golden Syrian hamsters with D-D2 strain showed its high immunogenicity: seroconversion was evident in all immunized animals. The absence of infectious virus in the lung, nasal passages, and brains of immunized animals allows us to characterize immunity to SARS-CoV-2 as "sterile" consistent with the viral RNA concentration in the organs on the fourth-day post-challenge. Comparison of data on viral reproduction in organs, weight dynamics, and morphological changes in the lungs of immunized and unimmunized hamsters showed that attenuated Wuhan-like D-D2 strain provides highly effective protection against infection and development of pneumonia when challenged both with ancestral virus and heterologous Delta (B.1.617.2.122) and Omicron (sublineages BA.1 and BA.5.2) variants. Thus, attenuated SARS-CoV-2 variants have great potential for the development of highly effective nasal live COVID-19 vaccines on their basis.