Development of a SARS-CoV-2 vaccine

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications, trials & patents

Abstract

In 2023, we extended our previous testing of an MVA-based SARS-CoV-2 vaccine by comparing intramuscular (IM) and intranasal (IN) delivery in mice. Although immunization by both routes induced binding and neutralizing antibodies in the lungs, IN also induced IgA and higher levels of antigen-specific T cells. The vaccine delivered by either route protected against severe disease, but SARS-CoV-2 was more rapidly cleared from the respiratory tract following IN immunization. In addition, we employed recombinant MVAs (rMVAs) expressing modified S of several SARS-CoV-2 strains and compared their ability to neutralize variants, bind S proteins and protect K18-hACE2 mice against SARS-CoV-2 challenge The rMVAs expressing Wuhan, Beta and Delta S induced substantial cross neutralizing activities to each other but very low neutralization of Omicron; while rMVA expressing Omicon S induced neutralizing antibody predominanly to Omicron. In mice primed and boosted with rMVA expressing the Wuhan S, neutralizing antibodies to Wuhan increased after one immunization with rMVA expressing Omicron S due to original antigenic sin, but substantial neutralizing antibody to Omicron required a second immunization. Nevertheless, monovalent vaccines with S mismatched to the challenge virus still protected against severe disease and reduced the amounts of virus and subgenomic RNAs in the lungs and nasal turbinates, though not as well as vaccines with matched S. Passive transfer of Wuhan immune serum with Omicron S binding but undetectable neutralizing activity reduced infection of the lungs by Omicron suggesting additional effector functions.