Safety, Immunogenicity, and Protective Efficacy in Rhesus Macaques of a Novel Recombinant Hemagglutinin Protein Measles Virus Vaccine

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BACKGROUND: Measles-mumps-rubella (MMR) is an effective live virus vaccine against measles but can be poorly immunogenic in young infants and contraindicated for pregnant and immunocompromised persons. METHODS: We evaluated immunogenicity and protective efficacy of a novel recombinant dimeric measles virus hemagglutinin protein vaccine (rMeV) in rhesus macaques. Macaques (n = 4) in 4 experimental groups were injected at days 0 and 42 with (1) MMR/MMR; (2) rMeV/rMeV; (3) MMR/rMeV; or (4) phosphate-buffered saline (PBS)/PBS and challenged intratracheally with wild-type measles virus (MeV) 8-9 months later. Blood, nasopharyngeal (NP), bronchoalveolar lavage (BAL), bone marrow (BM), and lymph node (LN) samples were collected. RESULTS: All macaques that received a MeV-containing vaccine developed MeV-specific binding and neutralizing antibody titers that were similar at 169 days postvaccination, regardless of experimental group. After challenge, all unvaccinated macaques had MeV detected in samples of blood, NP, BAL, BM, and LN, and 1 developed a rash. No vaccinated macaque developed a rash or had detectable MeV in peripheral blood mononuclear cells, BM, or NP cells. However, MeV and MeV RNA were detected in BAL samples in all experimental groups, with the most virus and longest detection in rMeV-vaccinated animals. CONCLUSIONS: Immunization with rMeV protected macaques from rash, viremia, and systemic virus spread. Therefore, rMeV is protective against MeV disease and a promising option for patients unable to receive or respond to MMR.

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