Recombinant Lassa Fever and Rabies Vaccine Shows Promise in Animal Models

The burden of Lassa fever in endemic nations is exacerbated by the fact that there is no approved vaccine.

Lassa fever cases are not uncommon in West African nations such as Nigeria, where the largest outbreak of Lassa fever in the nation’s history is currently underway. According to the Nigeria Center for Disease Control, as of October 14th, there have been 2706 suspected cases, 536 of which have been confirmed.

But hope may be on the horizon for bringing a vaccine to the forefront of preventive efforts, as a novel investigational vaccine has shown promise in preclinical studies involving mouse and guinea pig models.

“As a major LF (Lassa fever) surge unfolds in Nigeria at the time of manuscript preparation, the necessity to fully understand the immunomechanisms of protection of LASV (Lassa virus) becomes an increasingly important and crucial task for LF (Lassa fever) vaccine development,” the authors write in the study published in Nature Communications.

Although Lassa fever usually presents mild symptoms, patients can also experience serious symptoms including hemorrhage, respiratory distress, and shock. According to the US Centers for Disease Control and Prevention (CDC), the most common complication of Lassa fever is deafness, which occurs in approximately one-third of infections and can result in permanent hearing loss.

Approximately 15% to 20% of hospitalized patients die from the illness with the highest death rates reported in women in the third trimester of pregnancy. There is an estimated 95% mortality in unborn infants of pregnant mothers who fall ill with Lassa fever.

In addition to the burden of Lassa fever, rabies is also a public health problem in African nations. According to the World Health Organization, 95% of the deaths related to rabies each year occur in Asia and Africa. While effective rabies vaccines and post-exposure vaccines exist, many of the areas where the virus is most deadly have limited resources available.

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 (NIH).

The vaccine candidate is an inactivated recombinant vaccine that expresses a codon-optimized Lassa virus glycoprotein and is adjuvanted by a TLR-4 agonist (GLA-SE). The vaccine was designed to protect against both Lassa fever and rabies by inserting genetic material from Lassa virus into a weakened rabies virus carrier. By doing this, the vaccine expresses surface proteins from both viruses which can create an immune response against both viruses.

In the investigation, the researchers found that the vaccine, when administered with GLA-SE adjuvant—an immune response-stimulating protein—antibodies against the viruses were created in mouse and guinea pig models. Additionally, the vaccine protected guinea pigs that were exposed to the Lassa virus 58 days post-vaccination.

The investigation also yielded results indicating that an increased level of non-neutralizing immunoglobulin G (IgG) antibodies that bind to the Lassa virus proteins do correlate with protecting against the virus. “Levels of this type of antibody could potentially be a Lassa fever correlate of protection used to determine vaccine efficacy,” the authors write.

"The major finding is that the vaccine is safe and efficacious in the small-animal laboratory model available," Reid Johnson, PhD, staff scientist in the Emerging Viral Pathogens Section of NIAID's Laboratory of Immunoregulation told Contagion®. "Vaccinated subjects developed effective humoral response that appears to be mediated, at least in part, by non-neutralizing antibodies against Lassa virus. The antibody titer against rabies virus was sufficient to provide protection against rabies.

The authors indicate that the next step for their research is to evaluate the vaccine candidate in non-human primates prior to advancing to clinical trials in human populations. Dr. Johnson also explained the the role of non-neutralizing antibodies is poorly understood and discovering how the mechanisms of action could provide opportunities to develop new antivirals and improving vaccines.