We are still likely years away from a hantavirus vaccine

A recent outbreak of the Andes (ANDV) strain of the hantavirus aboard a cruise ship has increased public interest in efforts towards a vaccine. However, a publicly available vaccine is likely still several years away.

ANDV causes Hantavirus Pulmonary Syndrome (HPS), which has a 30% to 50% fatality rate. Some research also indicated that the virus is a potential “superspreader”, where a single infected individual results in a disproportionately large number of secondary infections. ANDV is the only known strain of hantavirus that can transmit from human to human.

Several efforts towards a vaccine for ANDV are ongoing, including DNA-based and mRNA-based candidates.

DNA-based vaccine candidates

Gene-based platforms offer a programmable method to target specific viral segments. The leading DNA-based candidate for an ANDV vaccine, pWRG/AND-M, uses an expression plasmid containing the full-length M genome segment of ANDV. 

The vaccine expresses the G1(Gn) and G2(Gc) glycoproteins essential for eliciting neutralizing antibodies. The vaccine uses a spring-powered, needle-free jet injector, which is vital for the induction of potent immune responses. 

This vaccine candidate was developed by the Department of Molecular Virology at the United States Army Medical Research Insitute of Infectious Diseases (USAMRIID) in Maryland. Phase 1 trials were conducted at the Vaccine and Treatment Evaluation Unit (VTEU) at Cincinnati Children’s Hospital Medical Center. 

This vaccine does require a multidose regiment of up to four doses, which is not ideal for containing a rapid outbreak. Future development is focused on reducing the number of doses. 

mRNA vaccines

Scientists at the University of Texas Medical Branch (UTMB) hav developed a monocistronic linear mRNA platform that encodes the ANDV glycoprotein precursor (GPC), which is proteolytically cleaved into the Gn and Gc glycoproteins. 

In lethal Syrian hamster models, the vaccine provided sterilizing protection against ANDV, inducing neutralizing antibody responses and germinal center responses. 

At the University of Bath, researchers are using a method called ensilication to wrap the active vaccine ingredients in protective silica, allowing vaccines to remain stable at ambient temperatures. They are testing the platform with a new hantavirus vaccine antigen that has yielded immune responses in laboratory and animal models. 

Other gene-based vaccines and passive immunization

Researchers have also developed a vesicular stomatitis virus (VSV)-based vaccine that expresses the ANDV glycoproteins. This platform could provide cross-protection against ANDV and the Sin Nombre virus (SNV), another deadly hantavirus found in North America. 

Some candidates use adenovirus backbones to deliver ANDV proteins. These have been shown to successfully protect hamsters against lethal challenges. 

Beyond active vaccines, there is an effort toward passive immunization, which provides immediate protection by transferring antibodies. The leading candidate for this is a quadrivalent human polyclonal antibody treatment, SAB-163. The antibodies are produced in transchromosomal cows that have been genetically engineered to produce human antibodies. 

In preclinical testing, the antibodies have shown high efficacy in protecting lethal animal models from ANDV. It can also be used as a post-exposure prophylactic. 

While many ANDV vaccine candidates have been in development for years, there are multiple obstacles still to overcome. Experts are concerned that the rarity and geographic dispersion of hantavirus cases could make a Phase 3 efficacy trial difficult. Additionally, a reliable surrogate endpoint is still needed to enable regulatory agencies to employ accelerated approval pathways. Altogether, it is more than likely that it will be several years before a vaccine against ANDV becomes available.