An experimental chikungunya vaccine to induce neutralising immune responses to kill the viruses once they enter the body has shown promise in mice.
Mice vaccinated with the vaccine were “partially protected” even when they were infected with a high dose of chikungunya virus. In nature, the viral load will be much lower when it is transmitted by a mosquito. In all probability, the protective effect of the vaccine may be “sufficient to protect against a mosquito derived infection.”
The prophylactic ability of the vaccine can be enhanced if it is used with an appropriate adjuvant (a compound that can increase the immune response). Currently, no vaccine is commercially available against chikungunya. The results were published a few days ago in the journal PLOS Neglected Diseases .
The chikungunya virus (CHIKV) is transmitted by Aedes mosquitoes and causes an infection in humans known as chikungunya fever. The disease causes fever and severe joint pain; the joint pain can last for a few months and in some cases for up to several years. India is one of the worst affected countries.
The chikungunya virus has two surface proteins — E1 and E2. While E1 is a fusion protein, E2 very likely plays a role in binding the virus with receptors seen on human cells. The E2 has three domains — A, B, and C. Of the three, the domain C is not accessible to antibodies and of little use in vaccine development. To produce a protein vaccine, researchers at Paul-Ehrlich-Institut, Langen, Germany, selected different areas in domain A and B and stitched them together.
After producing them in E. coli and purifying them, mice were immunised with these protein fragments. Their ability to produce neutralising antibodies in mice was studied post injection. Of the many protein fragments studied, the sAB+ proved to be the most efficient in producing neutralising antibodies. The researchers also generated a recombinant Modified Vaccinia Ankara (MVA) using the sAB+ construct.
The MVA is a vector that is used to carry the molecule of interest (which in this case is a protein) into the body of mice/humans. The MVA vectors were used in the AIDS vaccine trail carried out at the Chennai-based National Institute for Research in Tuberculosis.
Besides the recombinant protein sAB+ vaccine, two different vaccine combinations were tested — MVA-CHIKV-sAB+ and/or recombinant protein sAB+. The mice were then infected with the wild-type chikungunya virus two weeks after the final dose of the vaccine.
The recombinant protein vaccine showed greater reactivation compared with the recombinant MVA vaccine. Not surprisingly, vaccination using the recombinant protein vaccine “markedly reduced” the viral load after the mice were infected with chikungunya virus.
The recombinant MVA vaccine did not show any significant protection when used alone or in combination with the recombinant protein.
The researchers say that since the mice were infected with a very high dose of chikungunya virus, the protective effect of the recombinant protein vaccine may be “sufficient to protect against a mosquito derived infection.”