Bharat Biotech’s Zika virus vaccine confers 100% protection in mice

zika-microcephaly - Photo WHO
The vaccine made using an African strain confers 100% protection against infection and mortality caused by Asian and African Zika virus strains.

The Hyderabad-based Bharat Biotech’s killed (inactivated) Zika virus vaccine using an African strain (MR 766) has shown 100% efficacy against mortality and disease in animal studies. A ‘killed virus vaccine’ or ‘inactivated vaccine’ contains virus that has been grown in culture and then killed using physical or chemical processes. The whole virus was used for developing the vaccine.

Two doses (5 and 10 microgram) of the vaccine given through intramuscular route on days 0 and 21 to mice were found to protect the animals against Zika virus seven days after the second vaccination. The vaccine was found to confer 100% protection against infection caused by an Asian Zika virus strain as well as by the African Zika virus strain.

All the animals that were not vaccinated died eight days after infection by the African strain of the virus and 12 days after infection by the Asian strain. All the mice that did not receive the vaccine showed progressive morbidity before succumbing to infection.

While all the animals that received the vaccine exhibited “undetectable” viral load, the amount of virus present in animals that did not receive the vaccine peaked four days after being infected with either the African or Asian Zika virus strain. The results of the study were published in the journal Scientific Reports.

AG129_mouse
The AG129 mouse is highly immunocompromised.

“The vaccine was developed using the African strain of the virus. It is important to prove that the vaccine developed with the African strain also protects against Zika infection caused by the contemporary Asian strains of Zika virus. Importing the contemporary Asian strains into the country was difficult, and hence the vaccine challenge studies with Asian strain had to be outsourced to a CRO in the U.S.,” says Dr. K. Sumathy from Bharat Biotech and the first author of the paper.

A particular kind of mouse — AG129 — which is highly immunocompromised and hence highly susceptible to virus infection was used for studying the protection conferred by the vaccine against Zika virus, disease pathogenesis and mortality. All the AG129 animals that received the vaccine showed 100% protection against the virus, demonstrating the superior efficacy of the vaccine.

Immunogenicity studied

Additionally, the level of immune response induced by the vaccine was also studied using another kind of mouse model — Balb/c mice. Unlike the AG129 mice, this mouse model is immunocompetent and elicits full spectrum of immune response. Animals that received the vaccine developed Zika neutralising antibodies on day 14 after the first dose and a week after the second dose. When the animals were infected with Zika virus post-vaccination, the virus in the vaccinated animals was “undetectable”, while 72-96 hours after infection it peaked in animals that did not receive the vaccine.

“In both the mice models, the vaccine-induced protective immunity against virus challenge was observed,” says Dr. Sumathy. “The vaccine was made only with the African virus strain, but the vaccinated mice was challenged [infected] with both the African and the Asian strains. Our vaccine offered equivalent protection against challenge with both the African and the Asian strains of Zika virus.”

Though 5 and 10 microgram of the vaccine were tested, the amount of antibodies elicited by the higher dose was “not significantly” higher than that elicited by 5 microgram of the vaccine, says Dr. Sumathy. Vaccination protected the animals against Zika virus and disease up to 14 and 20 days after being challenged with the virus.

Passive immunisation

Bharat Biotech also carried out passive immunization studies to show that the Zika vaccine-induced antibodies confer protection against the virus in mice that were exposed to the virus. Rabbits were vaccinated with the vaccine and the vaccine-induced antibodies were given to mice. While no virus was detected in mice 24-144 hours after passive immunisation, the viral load peaked 72-96 hours in mice that did not receive the vaccine-induced antibodies.

“Our study shows that the choice of Zika virus strain may not be a limiting factor in vaccine development,” she says.

Published in The Hindu on April 17, 2017

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