Minks are highly susceptible to SARS-CoV-2,and have transmitted SARS-CoV-2 to humans.Oral immunization is one of the most promising strategies to prevent SARS-CoV-2 infection and transmission in minks.Here,we generate...Minks are highly susceptible to SARS-CoV-2,and have transmitted SARS-CoV-2 to humans.Oral immunization is one of the most promising strategies to prevent SARS-CoV-2 infection and transmission in minks.Here,we generated 3 recombinant rabies viruses(RABV),rERAG_(333E)/S6P,rERAG_(333E)/DS6P and rERAG_(333E)/BA2S6P,expressing the prefusion-stabilized SARS-CoV-2 spike protein of wild-type(S6P),δ(DS6P)or BA.2(BA2S6P)strain based on an oral rabies vaccine candidate(rERAG_(333E)).Oral or inactivated immunization of the 3 RABVs monovalent or trivalent were safe,and induced robust RABV neutralizing antibody and cross-antibody responses against the three SARS-CoV-2 in mice and minks.The challenge tests showed that 2 doses of rERAG_(333E)-S6P as an oral or inactivated vaccine completely protected mice against mouse-adapted SARS-CoV-2 infection in the upper and lower respiratory tracts,and largely prevented viral replication and lung damage caused by wild-type SARS-CoV-2infection in minks.Notably,we also confirmed that 2 doses of rERAG_(333E)-S6P as an oral or inactivated vaccine can largely protect minks against wild-type SARS-CoV-2 transmission via respiratory droplets.Our findings suggest that rERAG_(333E)-based COVID-19 vaccines appear to be suitable oral candidates to protect minks from SARS-CoV-2infection and transmission,and may serve as inactivated vaccines for further investigation in humans.展开更多
基金supported by the National Key Research and Development Program of China(2021YFC2301700)the Natural Science Foundation of Heilongjiang Province,China(YQ2022C040)。
文摘Minks are highly susceptible to SARS-CoV-2,and have transmitted SARS-CoV-2 to humans.Oral immunization is one of the most promising strategies to prevent SARS-CoV-2 infection and transmission in minks.Here,we generated 3 recombinant rabies viruses(RABV),rERAG_(333E)/S6P,rERAG_(333E)/DS6P and rERAG_(333E)/BA2S6P,expressing the prefusion-stabilized SARS-CoV-2 spike protein of wild-type(S6P),δ(DS6P)or BA.2(BA2S6P)strain based on an oral rabies vaccine candidate(rERAG_(333E)).Oral or inactivated immunization of the 3 RABVs monovalent or trivalent were safe,and induced robust RABV neutralizing antibody and cross-antibody responses against the three SARS-CoV-2 in mice and minks.The challenge tests showed that 2 doses of rERAG_(333E)-S6P as an oral or inactivated vaccine completely protected mice against mouse-adapted SARS-CoV-2 infection in the upper and lower respiratory tracts,and largely prevented viral replication and lung damage caused by wild-type SARS-CoV-2infection in minks.Notably,we also confirmed that 2 doses of rERAG_(333E)-S6P as an oral or inactivated vaccine can largely protect minks against wild-type SARS-CoV-2 transmission via respiratory droplets.Our findings suggest that rERAG_(333E)-based COVID-19 vaccines appear to be suitable oral candidates to protect minks from SARS-CoV-2infection and transmission,and may serve as inactivated vaccines for further investigation in humans.
