Active and Passive Immunization of Syrian Hamsters with An Attenuated SARS-CoV-2 Protects against New Variants of Concern

Abstract

Detection of secretory antibodies in the airway is highly desirable when evaluating mucosal protection by a vaccine against a respiratory virus like the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We show that a single intranasal delivery of an attenuated SARS-CoV-2 (Nsp1-K164A/H165A) induced both mucosal and systemic IgA and IgG in Syrian hamsters. Interestingly, either active or passive immunization of hamsters with Nsp1-K164A/H165A offered protection against heterologous challenge with variants of concern (VOCs) including Delta, Omicron BA.1, and Omicron BA.2.12.1. Among challenged animals, Nsp1-K164A/H165A vaccination specifically reduced viral loads in the respiratory tract and suppressed infection-induced macrophage accumulation and MX1 upregulation in the lung. The absence of variant-specific mucosal and systemic antibodies was associated with breakthrough infections, particularly of the nasal cavity following challenges with Omicron isolates. Together, our study demonstrates that an attenuated nasal vaccine may be developed to boost mucosal immunity against future SARS-CoV-2 VOCs.

Indirect Dispersion of SARS-CoV-2 Live-Attenuated Vaccine and Its Contribution to Herd Immunity

“…Vaccinated individuals develop a specific adaptive cellular and humoral immunity against a wide variety of viral antigens at the systemic and mucosal levels. Besides, due to its similarity with the wild virus, it also stimulates innate immunity [ 109 , 152 , 153 , 154 , 157 , 158 , 159 , 160 , 161 , 162 , 163 , 164 , 165 , 166 ]. Immunity induced by LAVs could allow the control of infections with new variants, avoiding severe infection symptoms and reducing the time of viral dispersal [ 109 , 149 , 167 , 168 ], leading to the reduction of new cases.…”