Modern biologics for rabies prophylaxis and the elimination of human cases mediated by dogs

ABSTRACT

Introduction: Rabies is a major viral zoonosis and neglected tropical disease, with a global distribution. Humans, domestic animals, and wild mammals are susceptible to infection. Etiological agents reside in the Order Mononegavirales, Family Rhabdoviridae, Genus Lyssavirus. This acute, progressive encephalitis causes the highest case fatality of any conventional infectious disease. Tens of millions of humans become exposed annually to the bites of infected mammals, predominantly in Asia and Africa. Despite the existence of effective vaccines and immune globulins, tens of thousands of people, typically children in the developing world, succumb.

Areas covered: Concentrating upon both historical and major published references from the peer-reviewed literature over the past 5 years, we describe current biologics for rabies prevention, newly recommended principles for prophylaxis, and relevant future products in the developmental pipeline.

Expert opinion: Modern human rabies biologics are pure, potent, safe, and efficacious, when used in a timely and appropriate manner. Few individuals survive after clinical signs. Anti-viral compounds are not licensed. Experimental therapy, while obviously desirable, is highly controversial. Education on bite prevention and integrated risk management are critical. Access to affordable care, dose-sparing, and shortened regimens of human rabies biologics remain key.

KEYWORDS:

• Antibodies
• encephalitis
• lyssavirus
• mononegavirales
• prophylaxis
• rabies
• rhabdovirus
• vaccine
• Virus
• zoonosis

Article highlights

• Rabies, an acute, progressive, incurable viral encephalitis, is the most important viral zoonosis, based on related case fatality (i.e., approaching 100%), global distribution on all inhabited continents, a susceptible host spectrum consisting of all mammals and an extreme burden (e.g., >14 million human exposures and 25,000 - 159,000 human fatalities estimated to occur annually, in lesser developed countries, primarily in children)

• As a vaccine-preventable disease, survivorship is virtually assured with appropriate biomedical intervention, in which modern biologics consist of safe, stable, effective cell and avian tissue culture vaccines, plus immune globulins or monoclonal antibodies (all developed during the 1970s-80s)

• Updated prophylaxis recommendations focus upon shorter vaccine schedules, dose-sparing regimens by the intradermal route of administration and concentration upon local infiltration of wounds with rabies immune globulins

• Although dogs are the most significant reservoir in lesser developed countries, all developed countries have eliminated canine rabies, and major geopolitical regions, such as Latin America, have made major progress towards this same goal, especially as mass canine vaccination is a cost-effective, long-term public health prevention strategy

• Human rabies mediated by dogs is targeted for global elimination by 2030, and by 2021, Gavi is expected to provide support for human rabies vaccines for post-exposure prophylaxis (subject to availability of funding for the 2021–2025 strategic period and alignment with the final parameters of its next strategy)

• Increased production, lower costs, and greater local availability of human biologics are expected to have a major impact in lessening the human rabies burden, and future biologics may include new adjuvants, protein sub-unit, nucleic acid-based or recombinant approaches

This box summarizes the key points contained in the article.

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 relationships or otherwise to disclose.

Additional information

Funding

This paper is not funded.