The vaccine against Lassa fever is promising and reveals a new test of immunity

Lassa fever belongs to the same class of haemorrhagic fevers as the Ebola virus. Like Ebola, it has been a major health threat in West Africa, infecting between 100,000 and 300,000 people and killing 5,000 people a year. A new rabies vaccine and Lassa has shown effective protection in animal models of disease, according to a study published in the journal Nature Communications, October 11th. The research also indicates a new way to test protection against the virus, a discovery that could significantly accelerate the development of the vaccine in humans.

"This two-component vaccine has shown good protection against exposure to both types of virus in preliminary animal studies," said lead author Matthias Schnell, director of the Department of Microbiology and Drug Therapy. 39, immunology at Jefferson (University of Philadelphia + Thomas Jefferson University) and director of the Jefferson Vaccination Center. Since the vaccine is inactivated and based on a rabies vaccine used for decades, its safety profile is excellent and probably safe enough to be administered to pregnant women at high risk of miscarriage if they are infected with Lassa virus. In addition, it can be produced in a freeze-dried and stable format, easy to use in clinics without a refrigeration system.

"Perhaps more importantly, though, we have discovered how to test protection, which could dramatically improve our ability to translate these findings into a ready-made vaccine," said Dr. Schnell.

The findings suggest a shift in how researchers will analyze the development potential of the Lassa vaccine and may also have implications for other haemorrhagic fever viruses.

Because it would be unethical to test the effectiveness of a vaccine by intentionally exposing people to a pathogen, vaccine researchers are instead looking for substitutes for it. Immunity, a substitute for immune protection, based on the results of animal studies.

One of the most common substitutes for vaccines against viral pathogens is the neutralizing antibody, one of the antibodies produced during an immune response that binds and blocks the part of the virus that Help to enter and infect the cells. "The neutralizing antibody acts as a glue on a key," says first author Tiago Abreu-Mota, MD / Ph.D. student of Dr. Schnell's laboratory visiting the University of Minho, Portugal . "By raising the key, or molecule of entry, the virus can no longer open the door to the cell."

Although the immune response generates antibodies that fight the infection in another way, the neutralizing antibody has been a kind of reference in vaccine development. High levels are usually a good indication that the immune response is strong enough to deflect the viral disease.

In the case of Lassa virus, however, neutralizing antibodies are not very good substitutes because they are produced in much smaller amounts.

Dr. Schnell, in collaboration with colleagues from the National Institutes of Allergy and Infectious Diseases (NIAID) and the University of California at San Diego (UCSD), examined antibodies against others. parts of the Lassa virus glycoprotein. Although these antibodies can not block the infection, researchers have shown that, in the case of Lassa, they could be effective enough to tag the virus or cell infected with the virus with a tag, which would allow for more identification. rapid by other immune defense cells, such as natural cells. immune cell killer.

The researchers used this concept to develop a new test to quantify the number of cells killed by antibody staining / NK cell attack, thus creating a new surrogate for protection against Lassa virus haemorrhagic disease, based on flow cytometry. They also showed that a certain class of IgG against Lassa virus was beneficial.

The new surrogate for protection will contribute to the development of a more potent vaccine against Lassa virus. Researchers are also exploring other approaches to help determine the protection of a vaccine in the field.

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More information:
Tiago Abreu-Mota et al., Non-neutralizing antibodies produced by the recombinant Lassa-Rabies vaccine are essential for protection against Lassa fever. Nature Communications (2018). DOI: 10.1038 / s41467-018-06741-w