Replication-restricted modified vaccinia virus Ankara (MVA) is a licensed
smallpox vaccine and numerous clinical studies investigating recombinant MVAs (rMVAs) as vectors for prevention of other
infectious diseases have been completed or are in progress. Two rMVA
COVID-19 vaccine trials are at an initial stage, though no animal protection studies have been reported. Here, we characterize rMVAs expressing the S
protein of CoV-2. Modifications of full length S individually or in combination included two
proline substitutions, mutations of the
furin recognition site and deletion of the endoplasmic retrieval signal. Another rMVA in which the receptor binding domain (RBD) flanked by the
signal peptide and transmembrane domains of S was also constructed. Each modified S
protein was displayed on the surface of rMVA-infected human cells and was recognized by anti-RBD antibody and by soluble hACE2 receptor.
Intramuscular injection of mice with the rMVAs induced S-binding and pseudovirus-
neutralizing antibodies. Boosting occurred following a second homologous rMVA but was higher with adjuvanted purified RBD
protein.
Weight loss and lethality following intranasal
infection of transgenic hACE2 mice with CoV-2 was prevented by one or two immunizations with rMVAs or by passive transfer of serum from vaccinated mice. One or two rMVA vaccinations also prevented recovery of infectious CoV-2 from the lungs. A low amount of virus was detected in the nasal turbinates of only one of eight rMVA-vaccinated mice on day 2 and none later. Detection of
subgenomic mRNA in turbinates on day 2 only indicated that replication was abortive in immunized animals.