Candidate vaccines for human Rift Valley fever

ABSTRACT

Introduction: Rift Valley fever (RVF) outbreaks can cause devastating economic loss and public health concerns. RVF virus (RVFV: genus Phlebovirus family Phenuiviridae) is transmitted by mosquitoes, causes abortion in sheep, cattle, and goats, and severe diseases in humans including hemorrhagic fever, encephalitis, or retinitis. RVFV has spread from sub-Saharan Africa into Madagascar, Egypt, Saudi Arabia, and Yemen.

Area covered: There are a few licensed veterinary RVF vaccines in endemic countries, whereas no licensed RVF vaccines are available for human use. There are two Investigational New Drug (IND) RVF candidate vaccines used in clinical trials. This review will discuss the development of two IND vaccines for RVF over the past 20–40 years, and further innovation for future RVF vaccines applicable for the use in endemic areas.

Expert opinion: Vaccination for human RVF can protect at-risk personnel against severe RVF illness. Formalin-inactivated RVF candidate vaccine requires three doses to induce protective immunity, whereas the live-attenuated MP-12 candidate vaccine retains strong immunogenicity. Further innovation in safety, immunogenicity, and thermostability will facilitate future RVF vaccines for humans.

KEYWORDS:

• Clinical trial
• Investigational New Drug
• Rift Valley fever
• vaccine
• thermostability

Article highlights

• The formalin-inactivated RVFV Entebbe strain, TSI-GSD-200, can induce a PRNT₈₀ titer of ≥1:40 in humans after three primary doses, with a half-life of 315 days.

• The live-attenuated MP-12 candidate vaccine, TSI-GSD-223 can induce long-term protective immunity in humans with a single dose.

• A live-attenuated RVF vaccine should support the safety of target populations, perhaps in a manner similar to that of the YF vaccine.

• Thermostability of a live-attenuated vaccine could be improved via formulation with stabilizers.

• ChAdOx1-GnGc has excellent stability at 37°C for six months and exhibits better immunogenicity than TSI-GSD-200

This box summarizes key points contained in the article.

Acknowledgments

The author would like to thank for Dr. John C. Morrill for valuable information regarding past MP-12 candidate vaccine studies.

Declaration of interest

T. Ikegami has received funding supports from the Institute for Human Infections and Immunity (IHII) and from The University of Texas Medical Branch at Galveston (UTMB). The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This research was funded by the Institute for Human Infections and Immunity (IHII) and The University of Texas Medical Branch at Galveston (UTMB).