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

病毒学 医学 免疫原性 麻疹病毒 接种疫苗 麻疹 皮疹 埃利斯波特 血凝素(流感) 病毒血症 麻疹疫苗 免疫学 风疹 麻疹腮腺炎风疹疫苗 中和抗体 MMR疫苗 病毒 抗体 免疫系统 T细胞 内科学
作者
Jessica Rubens,Jacqueline Brockhurst,Shristi Ghimire,Jinjin Wu,Li‐Ting Liu,Jason Villano,Rebecca J. Loomis,Alexandrine Derrien-Colemyn,Tracy J. Ruckwardt,Barney S. Graham,Mick Watson,Guillaume Stewart-Jones,Diane E. Griffin
出处
期刊:The Journal of Infectious Diseases [Oxford University Press]
标识
DOI:10.1093/infdis/jiaf244
摘要

Abstract 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.

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