Scientists develop an investigational vaccine for Lassa Fever and Rabies

Lassa fever (LF) is a viral hemorrhagic fever (VHF) caused by the Lassa virus (LASV). The etiologic agent in this fever is LASV, a bio-safety level 4 pathogen (BSL-4) pathogen. There is currently no potent antiviral treatment or an approved vaccine for the treatment of LF. Similar to other VHFs like the Marburg virus, and Ebola virus, LF can also be lethal. Development of vaccines against emerging viral pathogens became apparent after the Ebola epidemic in West Africa (2014-2016). Most BSL-4 pathogens cause geographically confined outbreaks; however, LF is believed to be a widespread epidemic throughout West Africa with an estimation of 100,000 to 300,000 humans being infected annually.1,2

Rabies, along with LF, is a major health burden in West Africa and is a World Health Organization (WHO) priority disease. WHO estimates that 59,000 human rabies deaths occur per year in Asia and Africa. Centers for Disease Control and Prevention state that, in spite of post-exposure shots and rabies vaccines, deaths continue to occur in resource-limited countries.2 Nigeria experienced its largest LF outbreak in the year 2018 with 134 deaths and 514 confirmed cases from January 1 to September 30. With increasing globalization and climatic changes, the possibilities of LF becoming a global threat increase, making developing a vaccine for LASV a high priority.2

As per new research published in Nature Communications, a novel vaccine that was designed to protect people from LF as well as from rabies showed promising results in preclinical testing. Scientists at the Thomas Jefferson University, Philadelphia; National Institute of Allergy and Infectious Diseases; University of California, San Diego; and University of Minho, Braga, Portugal, developed and tested a new vaccine named LASSARAB.2

A weakened rabies virus vector or carrier was used in this inactivated recombinant vaccine. For the vaccine to express surface proteins from both LASV and the rabies virus, researchers inserted genetic material from the LASV into the rabies virus vector. The surface proteins then provided a prompt immune response against both the LASV and the rabies virus. The live rabies virus was killed by inactivating the recombinant vaccine to make the carrier.2

Findings of the recently published studies show that LASSARAB, when administered with GLA-SE adjuvant (an immune response–stimulating protein), produces antibodies in guinea pig and mouse models against LASV and rabies virus. Even after being exposed to the virus after 58 days of vaccination, the vaccine protected the guinea pigs from LF.2

According to previous research, there is no correlation between antibody-mediated immune response and protection from LF. However, new research indicates that protection against LASV correlates with high levels of non-neutralizing immunoglobulin G antibodies that bind to LASV surface protein. According to the authors, the antibody levels produced could be an LF correlate of protection used to ascertain vaccine efficacy. The authors note that before advancing to human clinical trials, the next step is to evaluate this experimental vaccine in nonhuman primates.2

References:

  1. Abreu-Mota T, Hagen KR, Cooper K, et al. Non-neutralizing antibodies elicited by recombinant Lassa–Rabies vaccine are critical for protection against Lassa fever. Nat Commun. https://www.nature.com/articles/s41467-018-06741-w
  2. National Institutes of Health. Scientists develop novel vaccine for Lassa fever and rabies 2018 https://www.nih.gov/news-events/news-releases/scientists-develop-novel-vaccine-lassa-fever-rabies

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