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Published on: December 23, 2016
Safety, Immunogenicity, and Protective Efficacy in Rhesus Macaques of a Novel Recombinant Hemagglutinin Protein
Jessica H Rubens1,2, Jacqueline K Brockhurst2,3, Shristi Ghimire2
1Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
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.
Insights
A new recombinant measles virus (MeV) hemagglutinin protein vaccine (rMeV) shows promise for measles prevention. This rMeV vaccine protected macaques from measles disease, offering an alternative for those who cannot receive the Measles-Mumps-Rubella (MMR) vaccine.
Area of Science:
- Virology
- Vaccinology
- Immunology
Background:
- The Measles-Mumps-Rubella (MMR) vaccine is effective but has limitations in infants and is contraindicated for certain populations.
- Measles virus (MeV) infection poses a significant public health concern.
Purpose of the Study:
- To evaluate the immunogenicity and protective efficacy of a novel recombinant dimeric MeV hemagglutinin protein vaccine (rMeV).
- To assess rMeV as a potential alternative to the MMR vaccine.
Main Methods:
- Rhesus macaques were vaccinated with either MMR, rMeV, or a combination, alongside a control group.
- Animals were challenged with wild-type MeV 8-9 months post-vaccination.
- Samples from blood, nasopharyngeal lavage, bronchoalveolar lavage, bone marrow, and lymph nodes were analyzed.
Main Results:
- All MeV-vaccinated macaques developed MeV-specific antibodies.
- Unvaccinated macaques showed MeV presence across multiple sample types post-challenge, with one developing a rash.
- While MeV was detected in bronchoalveolar lavage samples of all vaccinated groups, vaccinated macaques were protected from rash, viremia, and systemic spread.
Conclusions:
- The rMeV vaccine demonstrated protective efficacy against MeV disease in a macaque model.
- rMeV is a promising alternative for individuals who cannot receive or respond adequately to the MMR vaccine.
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