An overview of human leptospirosis vaccine design and future perspectives

ABSTRACT

Introduction: It’s been 20 years since the first report of a recombinant vaccine that protected against leptospirosis. Since then, numerous recombinant vaccines have been evaluated; however, no recombinant vaccine candidate has advanced to clinical trials. With the ever-increasing burden of leptospirosis, there is an urgent need for a universal vaccine against leptospirosis.

Areas covered: This review covers the most promising vaccine candidates that induced significant, reproducible, protection and how advances in the field of bioinformatics has led to the discovery of hundreds of novel protein targets. The authors also discuss the most recent findings regarding the innate immune response and host–pathogen interactions and their impact on the discovery of novel vaccine candidates. In addition, the authors have identified what they believe are the most challenging problems for the discovery and development of a universal vaccine and their potential solutions.

Expert opinion: A universal vaccine for leptospirosis will likely only be achieved using a recombinant vaccine as the bacterins are of limited use due to the lack of a cross-protective immune response. Although there are hundreds of novel targets, due to the lack of immune correlates and the need for more research into the basic microbiology of Leptospira spp., a universal vaccine is 10–15 years away.

KEYWORDS:

• Leptospira
• universal vaccine
• reverse vaccinology
• structural vaccinology

Declaration of interest

The authors have 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 or other relationships to disclose.

Article highlights

• With the ever-increasing burden of leptospirosis to both human and animal health, there is an urgent need for a universal vaccine against leptospirosis.

• The application of reverse and structural vaccinology, including epitope mapping, has resulted in the identification of hundreds of novel vaccine candidates.

• Progress is being hampered by the lack of correlates of immunity and knowledge gaps in the basic microbiology of Leptospira spp.

• The Lig proteins and several other OMPs have conferred significant protection in animal models of leptospirosis, albeit with varying degrees of efficacy.

• Although there are several reports of cross-protection in the literature this remains one of the major challenges in the development of a universal vaccine for leptospirosis.

• While several adjuvants have been evaluated, aluminum hydroxide has provided the most reproducible results.

This box summarizes key points contained in the article.

Supplementary material

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Additional information

Funding

A McBride and J McFadden are supported by a research grant from the Royal Society [IC170171]. A McBride is also supported by a stipend from the Brazilian National Council for Scientific and Technological Development [CNPq - 311460/2017-8]. CR Felix and BS Siedler are also the recipients of postdoctoral stipends from the Royal Society (IC170171) while LN Barbosa is the recipient of a PhD stipend and GR Timm the recipient of an MSc stipend from CAPES, Brazil.