Vaccines and Therapeutics Against Hantaviruses

Abstract

Hantaviruses (HVs) are rodent-transmitted viruses that can cause hantavirus cardiopulmonary syndrome (HCPS) in the Americas and hemorrhagic fever with renal syndrome (HFRS) in Eurasia. Together, these viruses have annually caused approximately 200,000 human infections worldwide in recent years, with a case fatality rate of 5-15% for HFRS and up to 40% for HCPS. There is currently no effective treatment available for either HFRS or HCPS. Only whole virus inactivated vaccines against HTNV or SEOV are licensed for use in the Republic of Korea and China, but the protective efficacies of these vaccines are uncertain. To a large extent, the immune correlates of protection against hantavirus are not known. In this review, we summarized the epidemiology, virology, and pathogenesis of four HFRS-causing viruses, HTNV, SEOV, PUUV, and DOBV, and two HCPS-causing viruses, ANDV and SNV, and then discussed the existing knowledge on vaccines and therapeutics against these diseases. We think that this information will shed light on the rational development of new vaccines and treatments.

Keywords: HFRS; HPCS; hantavirus; therapeutic strategies; vaccine.

FIGURE 1

The distribution map of the average hantavirus cases in China of recent years. The main provinces shown in the map were Shaanxi: SN; Heilongjiang: HL; Liaoning: LN; Hebei: HE; Hubei: HB; Jilin: JL; Jiangxi: JX; Zhejiang: ZJ; Jiangsu: JS; Inner Mongoria: IM; Beijing: BJ; Yunnan: YN; Chongqing: CQ. The bar represents the annual average number of cases. These data were published by Chinese literatures.

FIGURE 2

US hantavirus cases from 1993 to 2018. These data were published by the Centers for Disease Control and Prevention, United States.

FIGURE 3

Hantavirus phylogenetic tree on the basis of the M segment sequences. A maximum clade credibility tree of the complete amino acid sequence of the protein encoded by the M segment of viruses belonging to Hantavirus. Different colors represent different clade. These proteins had a high similar signature domain and highly unconserved terminal sequences, which could artificially create similarities between sequences if the alignment was not properly made. Therefore, the phylogenetic tree was made with more robust methods using T-Coffee (default parameter, removed the unconserved sites by filtering the column scores < 4) for multiple sequence alignment and SMS-PhyML (default parameter, bootstrap = 1000, best model = LG +G) for ML (Maximum Likelihood) tree construction.