Post-exposure prophylactic vaccine candidates for the treatment of human Risk Group 4 pathogen infections

ABSTRACT

Introduction: The development of therapeutics and vaccines to combat Risk Group 4 pathogens, which are associated with high case-fatality rates, is a high priority. Postexposure prophylactic vaccines have the potential to bridge classical therapeutic and vaccine applications, but little progress has been reported to date.

Areas covered: This review provides an overview of postexposure prophylactic vaccine candidates against Risk Group 4 pathogens.

Expert opinion: A few candidate postexposure prophylactic vaccines protect experimental animals infected with a few Risk Group 4 pathogens, such as filoviruses or hantaviruses, but the efficacy of candidate vaccines has not been similarly reported for most other high-consequence pathogens. A major drawback for the further development of existing candidates is the lack of understanding of their mechanisms of action, knowledge of which could help to identify focused paths forward in vaccine development and licensure. These drawbacks to further development ultimately slow progress toward postexposure prophylactic vaccine licensure.

KEYWORDS:

• Biosafety level 4
• BSL-4
• postexposure prophylaxis
• Risk Group 4
• VSIV
• VSV

Article highlights

• PEP vaccines have the potential to be effective tools against diseases caused by RG-4 pathogens. However, research on RG-4 pathogen PEP vaccines is relatively lacking compared to research on other treatments and preventative measures.

• PEP candidate vaccines against ANDV, EBOV, MARV, and SUDV have been tested successfully in some animal models.

• The rVSIV vaccine vector is the best-studied PEP vaccine platform in RG-4 pathogen research and has been developed for multiple viruses. However, a few alternatives, including a VLP vaccine, are efficacious in certain animal models.

• Innate immune activation may play a role in the PEP elicited by available candidate vaccines.

• Further animal model development is needed to more strictly model disease progression in humans to further define the therapeutic window of PEP vaccines.

• Research into different types of vaccines and vaccination regimens may broaden the search for an effective PEP vaccine treatment.

• Only one ring vaccination trial using a rVSIV-vectored vaccine against EBOV has been published in a peer reviewed, scientific journal. Future trials may benefit from the inclusion of baseline and subsequent blood draws for serological and viral quantification testing to raise confidence in trial results.

• No research into PEP vaccines has been reported for many important RG-4 pathogens, including Crimean-Congo hemorrhagic fever and Nipah viruses.

Acknowledgments

The authors thank Laura Bollinger (NIH/NIAID Integrated Research Facility at Fort Detrick, Frederick, MD, USA) for critically editing the manuscript.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Additional information

Funding

This work was supported in part through Battelle Memorial Institute’s prime contract with the US National Institute of Allergy and Infectious Diseases (NIAID) under Contract No. HHSN2722007000161 (J.L., J.H.K.) and with federal funds from the National Cancer Institute (NCI), National Institutes of Health (NIH), under Contract No. HHSN261200800001 (I.C.).