Intranasal administration of cold-adapted live-attenuated SARS-CoV-2 candidate vaccine confers protection against SARS-CoV-2

Cold-adapted SARS-CoV-2 variants with different temperature sensitivity exhibit an attenuated phenotype and confer protective immunity

“…Single intranasal immunization with D-B4 and D-D2 variants induced the production of neutralizing antibodies in Syrian hamsters and protected them from infection with the D strain and consequent development of severe pneumonia. This is consistent with the results of similar studies [22] , [23] , [24] , [34] revealing high protective activity of attenuated SARS-CoV-2 strains by intranasal immunization of Syrian hamsters or hACE-2 (K18-hACE2) transgenic mice.…”

“…Previously, S.H. Seo et al, S. Okamura et al and M. Abdoli et al reported cold-adapted and temperature sensitive SARS-CoV-2 strains as vaccine candidates [22] , [23] , [24] . In the present study, we have shown that for ca variants of SARS-CoV-2, the ts phenotype is not mandatory for virulence reduction.…”

“…In this case, the cold-adapted ( ca ) attenuated virus provides safe and effective protection against wild-type virus infection [20] , [21] . Recently, scientific groups from Japan, Korea and Iran reported ca attenuated SARS-CoV-2 strains exhibiting a ts phenotype [22] , [23] , [24] . In this work, we generated two ca live attenuated SARS-CoV-2 clones with different temperature sensitivity and evaluated their virulence, immunogenicity, and protective activity in a Syrian golden hamster model of coronavirus pneumonia.…”

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

“…(c) combination of natural dispersion and massive vaccination: in some countries, the combination of natural infections and massive vaccination has resulted in a percentage of immune persons near the one required to achieve HI, even though in several of these countries, children have not been vaccinated [ 150 , 151 ] nor the individuals that oppose vaccination [ 136 , 137 , 138 , 139 , 140 , 141 , 142 ]. SARS-CoV-2 LAVs are still in preclinical and clinical studies, and it takes a longer time for their approval because more strict biosecurity criteria must be met [ 152 , 153 , 154 , 155 , 156 , 157 ].…”

“…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.…”