Lassa fever vaccine shows promise and reveals new test for immunity

October 11, 2018, Thomas Jefferson University
This transmission electron microscopic (TEM) image depicts Lassa virus virions adjacent to some cell debris. Credit: CDC/C.S. Goldsmith

Lassa fever belongs to the same class of hemorrhagic fevers as Ebola. Like Ebola, it has been a major health threat in Western Africa, infecting 100,000-300,000 people and killing 5,000 per year. A new vaccine against both rabies and Lassa has demonstrated effective protection in animal models of disease, according to research publishing in the journal Nature Communications, on October 11th. The research also points to a new way to test for protection against the virus, a finding that could significantly speed vaccine development in humans.

"This two-component showed good protection from exposure to both 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 results suggest a change in how researchers will analyze for potency in Lassa virus vaccine development, and could have implications for other hemorrhagic fever viruses as well.

Because it would be unethical to test vaccine efficacy by intentionally exposing people to a pathogen, vaccine researchers instead test for so-called surrogates of immunity, a proxy for immune protection, based on results from animal studies.

One of the most common surrogates for vaccines against viral pathogens is the neutralizing antibody—one of the antibodies made during an immune reaction that binds and blocks the part of the virus that helps it enter and infect . "The neutralizing antibody works like putting glue on a key," says first author Tiago Abreu-Mota, MD/Ph.D. student in Dr. Schnell's lab visiting from University of Minho, Portugal. "By junking-up the key, or entry molecule, the virus can no longer open the door to the cell."

Although the immune response generates antibodies that fight infection in other ways, the neutralizing antibody has been something of a gold standard in . High levels are usually a good indication that the immune reaction is strong enough to deflect viral disease.

In the case of Lassa virus, however, neutralizing antibodies have not been very good surrogates, since they are produced in much lower quantities.

Dr. Schnell, together with colleagues from the National Institutes of Allergy and Infectious Disease (NIAID) and University of California, San Diego (UCSD), looked at antibodies against other parts of the Lassa virus glycoprotein. Although these can't block the infection, the researchers showed that in the case of Lassa, they can be quite effective at tagging the virus or virus-infected cell with a beacon for quicker identification by other immune defense cells, such as the natural killer immune cell.

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

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

Explore further: DNA vaccine against Ebola virus shows potent and long-term efficacy in preclinical studies

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

Related Stories

DNA vaccine against Ebola virus shows potent and long-term efficacy in preclinical studies

October 10, 2018
A novel synthetic DNA vaccine developed based on technology pioneered by scientists at The Wistar Institute Vaccine & Immunotherapy Center offers complete protection from Zaire Ebolavirus (EBOV) infection in promising preclinical ...

Scientists identify protective role for antibodies in Ebola vaccine study

January 14, 2013
Researchers at the National Institutes of Health (NIH) and Oregon Health & Science University (OHSU) have found that an experimental vaccine elicits antibodies that can protect nonhuman primates from Ebola virus infection.

Why the latest shingles vaccine is more than 90 percent effective

March 7, 2018
A new study has shown how the body's immune system responds to the new shingles vaccine, Shingrix, making it more than 90% effective at protecting against the virus.

Researchers develop Lassa fever treatment effective eight days after infection

September 5, 2017
A collaborative team of scientists, led by a group at The University of Texas Medical Branch at Galveston, have successfully protected nonhuman primates against one of the most deadly viruses in the world, Lassa fever, eight ...

Researchers unravel pathways of potent antibodies that fight HIV infection

March 3, 2016
One of the most crucial and elusive goals of an effective HIV vaccine is to stimulate antibodies that can attack the virus even as it relentlessly mutates.

Recommended for you

Gene plays critical role in noise-induced deafness

October 19, 2018
In experiments using mice, a team of UC San Francisco researchers has discovered a gene that plays an essential role in noise-induced deafness. Remarkably, by administering an experimental chemical—identified in a separate ...

Functional engineered oesophagus could pave way for clinical trials 

October 18, 2018
The world's first functional oesophagus engineered from stem cells has been grown and successfully transplanted into mice, as part of a pioneering new study led by UCL.

New findings cast light on lymphatic system, key player in human health

October 16, 2018
Scientists at the Oklahoma Medical Research Foundation have broken new ground in understanding how the lymphatic system works, potentially opening the door for future therapies.

New model suggests cuffless, non-invasive blood pressure monitoring possible using pulse waves

October 16, 2018
A large team of researchers from several institutions in China and the U.S. has developed a model that suggests it should be possible to create a cuffless, non-invasive blood pressure monitor based on measuring pulse waves. ...

Age-related increase in estrogen may cause common men's hernia

October 16, 2018
An age-related increase in estrogen may be the culprit behind inguinal hernias, a condition common among elderly men that often requires corrective surgery, according to a Northwestern Medicine study was published Oct. 15 ...

Income and wealth affect the mental health of Australians, study shows

October 16, 2018
Australians who have higher incomes and greater wealth are more likely to experience better mental health throughout their lives, new research led by the Bankwest Curtin Economics Centre has found.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.