Scientists have produced a novel Lassa vaccine utilizing a recombinant measles virus and investigated its protective efficacy against Lassa illness. In monkeys with pre-existing immunity to the measles virus, a single vaccine dose elicited a quick and robust immunological response.
Background
Lassa fever, caused by the Lassa virus, is a major public health problem in West Africa. Because of non-specific symptoms such as fever, exhaustion, and headache, the disease is frequently discovered in its severe stages. In hospitalized patients, the disease has a case fatality rate of 15-30%.
The Lassa virus’s native habitat is rats of the Mastomys genus. Exposure to rodent-contaminated dust and infectious fluids causes animal-to-human transfer. Although supportive care and symptomatic treatment appear to enhance life in Lassa virus-infected patients, no effective vaccinations against this lethal disease are currently available.
The immunogenicity and protective effectiveness of the recombinant measles virus-based Lassa vaccine was investigated in monkeys with pre-existing immunity to the measles virus in the current investigation.
The vaccine was initially developed using a recombinant measles virus expressing the Lassa virus’s glycoprotein and the Josiah strain’s nucleoprotein. Following that, the vaccine was modified to boost immunogenicity.
Recent research has demonstrated that a single dose of this vaccine induces a significant immune response and protects monkeys against distinct strains of the Lassa virus.
The sole problem with delivering this vaccination to humans, as stated by the experts, is that pre-existing anti-measles immunity in humans may diminish vaccine efficacy. Given this worry, the researchers devised this trial to investigate vaccine efficacy in monkeys who already have anti-measles immunity.
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Lassa vaccine with measles virus protects against the disease
uniformly to tens of thousands of people (Josiah strain). One hour following the viral challenge, a separate group of monkeys was inoculated with the vaccine.
Clinical examination results demonstrated no clinical deterioration in vaccinated animals, however, non-vaccinated animals displayed clinical signs such as shivering, balance issues, and elevated body temperature. One hour after the viral challenge, the vaccinated animals developed clinical abnormalities such as nosebleeds.
In terms of biochemical parameters, non-vaccinated and 1-hour post-vaccinated animals showed a significant rise in markers of severe Lassa fever and inflammation. swags and swags like these.
Vaccinated animals are highly protected against significant inflammatory responses defined by elevated pro-inflammatory cytokines, chemokines, and cytolytic proteins, according to a multiplex investigation of various soluble mediators of inflammation.
Additionally, no infectious virus was found in the blood or other organs of the vaccinated animals. Non-vaccinated and 1-hour post-vaccinated animals, on the other hand, had higher levels of infectious virus and viral RNA in their blood and other organs.
Immune response to the Lassa vaccination based on the measles virus
The investigation of immunological responses in animals following a viral challenge demonstrated that vaccinated animals are capable of producing robust binding and neutralizing antibody responses against various Lassa virus proteins (glycoprotein and nucleoprotein). Following the exposure, these animals had a strong measles-specific antibody response.
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Non-vaccinated animals and 1-hour post-vaccinated animals, on the other hand, only had measurable levels of anti-Lassa virus antibody response at the end of the trial. In terms of measles-specific antibody response, non-vaccinated animals had detectable antibody levels throughout the investigation. Also, a progressive increase in measles-specific antibody response was found in 1-hour post-vaccinated mice over time.
In terms of cellular immunological response, vaccinated animals showed a significant increase in the number of circulating CD8+ T cells. This cytotoxic T-cell response was stronger in mice exposed to the virus 8 days after inoculation. Vaccinated animals also had an activated CD4+ T cell response. The transcriptome profiles obtained in peripheral blood mononuclear cells supported these findings even more. Overall, the findings suggest that CD8+ T cells are critical for controlling Lassa virus infection.
The relevance of the research
According to the study, a single dose of the Lassa vaccine based on the measles virus can provide significant protection against Lassa disease in monkeys with pre-existing anti-measles immunity. The vaccine, however, requires a short-term window of 8 to 16 days to generate robust humoral and cellular immune responses against the Lassa virus.
Monkeys inoculated eight days before the viral challenge have a stronger immune response than monkeys immunized sixteen days before the viral test. This suggests that the interval between immunization and viral challenge should be reduced. Unfortunately, the vaccine does not appear to have any therapeutic benefits because immunization following viral challenges fails to elicit an immunological response.
