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Published on: May 2, 2011
Recombinant measles virus vaccine expressing the Nipah virus glycoprotein protects against lethal Nipah virus
Misako Yoneda1, Marie-Claude Georges-Courbot, Fusako Ikeda
1Laboratory Animal Research Center, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan. yone@ims.u-tokyo.ac.jp
Abstract:
Nipah virus (NiV) is a member of the genus Henipavirus, which emerged in Malaysia in 1998. In pigs, infection resulted in a predominantly non-lethal respiratory disease; however, infection in humans resulted in over 100 deaths. Nipah virus has continued to re-emerge in Bangladesh and India, and person-to-person transmission appeared in the outbreak. Although a number of NiV vaccine studies have been reported, there are currently no vaccines or treatments licensed for human use. In this study, we have developed a recombinant measles virus (rMV) vaccine expressing NiV envelope glycoproteins (rMV-HL-G and rMV-Ed-G). Vaccinated hamsters were completely protected against NiV challenge, while the mortality of unvaccinated control hamsters was 90%. We trialed our vaccine in a non-human primate model, African green monkeys. Upon intraperitoneal infection with NiV, monkeys showed several clinical signs of disease including severe depression, reduced ability to move and decreased food ingestion and died at 7 days post infection (dpi). Intranasal and oral inoculation induced similar clinical illness in monkeys, evident around 9 dpi, and resulted in a moribund stage around 14 dpi. Two monkeys immunized subcutaneously with rMV-Ed-G showed no clinical illness prior to euthanasia after challenge with NiV. Viral RNA was not detected in any organ samples collected from vaccinated monkeys, and no pathological changes were found upon histopathological examination. From our findings, we propose that rMV-NiV-G is an appropriate NiV vaccine candidate for use in humans.
Insights
A novel recombinant measles virus (rMV) vaccine expressing Nipah virus (NiV) glycoproteins completely protected hamsters and non-human primates against NiV infection, showing promise as a human vaccine candidate.
Area of Science:
- Virology
- Vaccinology
- Infectious Diseases
Background:
- Nipah virus (NiV), a zoonotic paramyxovirus, causes severe respiratory and neurological disease in humans, with high mortality rates and no licensed vaccines or treatments.
- NiV outbreaks have re-emerged in South and Southeast Asia, highlighting the urgent need for effective preventative measures.
- Previous NiV vaccine development efforts have shown limited success in preclinical models.
Purpose of the Study:
- To develop and evaluate a novel recombinant measles virus (rMV) vaccine expressing NiV envelope glycoproteins (rMV-HL-G and rMV-Ed-G).
- To assess the efficacy of the rMV-NiV-G vaccine in hamster and non-human primate models against NiV challenge.
- To determine the safety and immunogenicity of the rMV-NiV-G vaccine in non-human primates.
Main Methods:
- Development of recombinant measles virus (rMV) vectors expressing Nipah virus (NiV) envelope glycoproteins (rMV-HL-G and rMV-Ed-G).
- Vaccination of hamsters and African green monkeys with rMV-NiV-G vaccine candidates.
- Challenge of vaccinated and control animals with NiV via various routes (intraperitoneal, intranasal, oral).
- Monitoring of clinical signs, mortality, viral RNA detection, and histopathological examination.
Main Results:
- Vaccinated hamsters demonstrated complete protection against NiV challenge, with 90% mortality in unvaccinated controls.
- Non-human primates vaccinated with rMV-Ed-G showed no clinical signs of NiV disease after challenge.
- No viral RNA was detected in organ samples, and no pathological changes were observed in vaccinated monkeys, indicating vaccine efficacy and safety.
- Unvaccinated non-human primates exhibited severe clinical signs and died within 7-14 days post-infection.
Conclusions:
- The recombinant measles virus vaccine expressing Nipah virus envelope glycoproteins (rMV-NiV-G) is a promising candidate for human use.
- The rMV-NiV-G vaccine demonstrated complete protection in preclinical models, including non-human primates.
- Further development of the rMV-NiV-G vaccine is warranted to address the global threat of Nipah virus infection.
