Safety, immunogenicity, and protective efficacy in rhesus macaques of a novel recombinant hemagglutinin protein measles virus vaccine.

BACKGROUND Measles-Mumps-Rubella (MMR) is an effective live-virus vaccine against measles but is poorly immunogenic in infants and contraindicated for pregnant and immunocompromised persons. METHODS We evaluated immunogenicity and protective efficacy of a novel recombinant dimeric MeV hemagglutinin protein vaccine (rMeV) in rhesus macaques. Macaques (n=4) in four experimental groups were injected at days 0 and 42 with: 1) MMR/MMR; 2) rMeV/rMeV; 3) MMR/rMeV; 4) PBS/PBS and challenged intratracheally with wild type MeV 8-9 months later. Blood, nasopharyngeal (NP), bronchoalveolar lavage (BAL), bone marrow (BM), and lymph nodes (LN) were sampled. RESULTS All macaques that received a MeV-containing vaccine developed MeV-specific binding and neutralizing antibody titers that were similar at 169 days post-vaccination, regardless of experimental group. After challenge, all unvaccinated macaques had MeV detected in samples of blood, NP, BAL, BM and LN, and one developed a rash. No vaccinated macaque developed a rash or had detectable MeV in PBMC, 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.