Developing Chikungunya Virus Vaccines – Learning from the Immune Response towards the Infection

The Chikungunya virus (CHIKV) is transmitted by aedes mosquitos such as the Asian tiger mosquito (Aedes albopictus) and causes Chikungunya fever in humans.

Scientists led by Prof. Barbara Schnierle, head of the „AIDS, New and Novel Pathogens“ department, and Dr. Sally Baylis, researcher in the Virus Safety department of the Paul-Ehrlich-Institut, in collaboration with researchers from Themis Bioscience GmBH, Austria, and the Instituto Oswaldo Cruz, Rio de Janeiro, Brazil, have investigated the generation of CHIKV-specific antibodies in individuals who had suffered from a CHIKV infection and recovered. This humoral immune response, i.e. the type and extent of antibody formation against the pathogen was compared with the formation of antibodies from healthy participants who had been vaccinated with a Chikungunya vaccine candidate. The vaccine candidate investigated in this study was a measles vector vaccine (MV-CHIK).

In the study, her team compared the type and extent of antibody formation with the formation of antibodies (humoral response) in healthy participants who had been vaccinated with a Chikungunya vaccine candidate (measles vector vaccine MV-CHIK). In those individuals who had undergone a CHIKV infection, CHIKV-specific antibody levels were two to six times higher than in vaccinated individual. As the main antigen structures against which the antibodies were formed, the research group identified a binding domain of the envelope protein E2 as well as so-called acid sensitive regions (ASPs) of the virus for both groups. Some of the antibodies raised against these regions, known as neutralising antibodies, were able to prevent the CHIKV from entering the host cell.

“The findings are helpful for the design of effective vaccines, the evaluation of the efficacy, and the identification of specific neutralising antibodies to prevent the Chikungunya virus from entering into the target cells,” as Professor Schnierle explained the significance of these results.

Background

The CHIKV is predominant in tropical and subtropical regions and has already caused epidemics in Africa, parts of the Indian Ocean regions, South-East Asia, the Caribbean, as well as Central and South America. Chinkungunya infections are reported regularly from people returning home from travels. The infection is notifiable in Germany. Since the Asian tiger mosquito is increasingly spreading and meanwhile also occurs in Germany, further spreading of the virus must be expected. Symptoms of a Chikungunya infection include fever and strong limb pain – a symptom from which the disease derives its name – Chikungunya means “the one who walks bent”. In 30 to 40 percent of the cases, this limb pain can last several months or even years. A vaccine is so far not available.

CHIKV is a single-strain RNA virus. Its envelope proteins E1 and E2 form docking sites on the surface of the virus, thus facilitating the infection in the host cell. CHIKV-specific antibodies are of major significance for the protection from the disease. Thus, mice were protected from a CHIKV infection after injection of CHIKV-specific monoclonal antibodies.

original publication:
Henss L, Yue C, von Rhein C, Tschismarov R, Lewis-Ximenez LL, Dölle A, Baylis SA, Schnierle BS (2019)
Analysis of humoral immune responses in chikungunya virus (CHIKV) infected patients and individuals vaccinated with a candidate CHIKV vaccine.
J Infect Dec 12 .
DOI:10.1093/infdis/jiz658

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