Houston, Texas, USA : A novel vaccine designed to protect people from both Lassa fever and rabies showed promise in preclinical testing, according to new research published in Nature Communications. The investigational vaccine, called LASSARAB, was developed and tested by scientists at Thomas Jefferson University in Philadelphia; the University of Minho in Braga, Portugal; the University of California, San Diego; and the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
The research also points to a new way to test for protection against the viruses, a finding that could significantly speed vaccine development in humans,
“This two-component vaccine showed good protection from exposure to both virus types in preliminary animal studies,” said senior author Matthias Schnell, Chair of the Department of Microbiology and Immunology at Jefferson (Philadelphia University + Thomas Jefferson University) and Director of the Jefferson Vaccine Center. Because the vaccine is inactivated and based on a rabies vaccine that has been used for decades, the safety profile of the combination vaccine is excellent and likely safe enough to administer to pregnant women, who have a high risk of miscarriage when infected with Lassa virus. In addition, it can be likely produced in a stable lyophilized format that is easy to use in clinics that lack refrigeration.
“Perhaps more importantly, however, we’ve discovered how to test for protection, which could vastly improve our ability to translate these findings into a human-ready vaccine,” said Dr. Schnell.
The inactivated recombinant vaccine candidate uses a weakened rabies virus vector, or carrier. The research team inserted genetic material from Lassa virus into the rabies virus vector so the vaccine expresses surface proteins from both the Lassa virus and the rabies virus. These surface proteins prompt an immune response against both Lassa and rabies viruses. The recombinant vaccine was then inactivated to “kill” the live rabies virus used to make the carrier.
There are currently no approved Lassa fever vaccines. Although Lassa fever is often a mild illness, some people experience serious symptoms, such as hemorrhage (severe bleeding) and shock. The overall Lassa virus infection case-fatality rate is about 1 percent, according to the World Health Organization (WHO), but that rate rises to 15 percent for patients hospitalized with severe cases of Lassa fever. People contract Lassa virus through contact with infected Mastomys rats and through exposure to an infected person’s bodily fluids. Lassa fever is endemic to West Africa where these rats are common.
In 2018, Nigeria experienced its largest-ever Lassa fever outbreak, with 514 confirmed cases and 134 deaths from Jan. 1 through Sept. 30, according to the Nigeria Centre for Disease Control (link is external).
Africa is also at high risk for human rabies. The WHO estimates that 95 percent of the estimated 59,000 human rabies deaths per year occur in Africa and Asia (link is external). Nearly all human rabies deaths are caused by bites or scratches from infected dogs. Effective rabies vaccines and post-exposure shots are available, but many deaths still occur in resource-limited countries (link is external), according to the Centers for Disease Control and Prevention.
The newly published findings show that LASSARAB, when administered with GLA-SE adjuvant (an immune response-stimulating protein), elicits antibodies against Lassa virus and rabies virus in mouse and guinea pig models. The vaccine also protected guinea pigs from Lassa fever after being exposed to the virus 58 days after vaccination.
Prior research indicated that an antibody-mediated immune response is not correlated with protection from Lassa fever, the authors note. However, the new findings show that high levels of non-neutralizing immunoglobulin G (IgG) antibodies that bind to the Lassa virus surface protein correlate with protection against Lassa virus. Levels of this type of antibody could potentially be a Lassa fever correlate of protection used to determine vaccine efficacy, according to the authors. They note the next step is to evaluate the experimental vaccine in nonhuman primates before advancing to human clinical trials.
Study : Tiago Abreu-Mota et al, Non-neutralizing antibodies elicited by recombinant Lassa–Rabies vaccine are critical for protection against Lassa fever, Nature Communications.