Vaccine Development for Severe Fever with Thrombocytopenia Syndrome

Abstract

Severe fever with thrombocytopenia syndrome (SFTS), which is caused by SFTS virus (SFTSV), is a tick-borne emerging zoonosis with a high case-fatality rate. At present, there is no approved SFTS vaccine, although the development of a vaccine would be one of the best strategies for preventing SFTS. This article focused on studies aimed at establishing small animal models of SFTS that are indispensable for evaluating vaccine candidates, developing these vaccine candidates, and establishing more practical animal models for evaluation. Innate immune-deficient mouse models, a hamster model, an immunocompetent ferret model and a cat model have been developed for SFTS. Several vaccine candidates for SFTS have been developed, and their efficacy has been confirmed using these animal models. The candidates consist of live-attenuated virus-based, viral vector-based, or DNA-based vaccines. SFTS vaccines are expected to be used for humans and companion dogs and cats. Hence for practical use, the vaccine candidates should be evaluated for efficacy using not only nonhuman primates but also dogs and cats. There is no practical nonhuman primate model of SFTS; however, the cat model is available to evaluate the efficacy of these candidate SFTS vaccines on domesticated animals.

Kinetics of Glycoprotein-Specific Antibody Response in Patients with Severe Fever with Thrombocytopenia Syndrome

“…Song et al demonstrated the neutralization activity of Gn-specific antibodies from convalescent patients [7]. In addition, a recombinant viral vector-based vaccine expressing the SFTSV glycoprotein or DNA vaccine encoding the SFTSV glycoprotein has been reported as a vaccine candidate for SFTS [18]. If further evidence of a protective effect of anti-Gn-specific IgG is provided by the neutralizing antibody assay, our Gn-specific antibody response data might be helpful in choosing a potential donor of convalescent plasma therapy or developing a vaccination strategy.…”

Humoral immunity to phlebovirus infection

“…While Phase 1 trials in humans have not yet been conducted for other phleboviruses, several approaches for SFTSV have been explored in animal models with varying degrees of success 66 . A DNA vaccine encoding full‐length Gn, Gc, N, NS, and RdRp genes of SFTSV generated both neutralizing antibodies and a T cell response that was able to protect from lethal challenge in a ferret challenge model 67 .…”

Highly adaptive Phenuiviridae with biomedical importance in multiple fields

“…Ferret and other animal models of some human phenuivirid diseases have been developed, which are valuable in developing therapeutics and preventive measures [14,154]. Live-attenuated virus-based, viral vectorbased, and DNA-based vaccines for SFTS, which are expected to be used for humans and companion dogs and cats, have been under investigation, and their efficacy has been confirmed using animal models [155], but none of them have entered clinical trials.…”

“…10,127 Live-attenuated virusbased, viral vector-based, and DNA-based vaccines for SFTS, which are expected to be used for humans and companion dogs and cats, have been under investigation, and their efficacy has been confirmed using animal models. 128 RVFV vaccines have been used in animals in endemic regions, and human RVFV vaccines have entered clinical trials. 129,130 Inactivated RVF candidate vaccine requires three doses and the live-attenuated MP-12 candidate vaccine requires only one dose to induce protective immunity.…”