The Lancet: Virus-like particle vaccine shows promise against chikungunya virus infection in first human trial

The first human trial of a new vaccine developed using non-infectious virus-like particles (VLP) appears likely to offer protection against chikungunya virus[1], a mosquito-borne infection, according to a study published in The Lancet. Since its re-emergence in 2004, chikungunya virus has become a growing public-health threat that has affected millions of people in Africa, Asia, and Europe, and in recent months it has been spreading throughout the Americas.

"Chikungunya virus has adapted itself to be transmitted by not only the Aedes aegypti mosquito that lives mainly in the tropics but also by the Asian tiger mosquito (Aedes albopictus) which is found in more temperate regions such as Europe and the Americas.  Since 2006, the virus has caused outbreaks of disease where it had never been previously reported, including Italy, France, and most recently, the USA"*, said study leader Dr Julie Ledgerwood at the National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA.

"Currently, we have no licensed vaccines or approved drugs for this debilitating infection, which causes fever and intensely painful, severe arthritis."*

Unlike other chikungunya virus candidates, this new vaccine consists of VLP composed of the outer structural proteins of the West African strain 37997, that would typically be seen by the immune system. Theses nanoparticles mimic the immune-stimulating effects of actual virus particles but cannot cause infection because they do not contain the genetic material of the virus. Earlier research in rhesus macaques showed that the candidate vaccine provided protection from infection.

The phase 1 trial included 25 healthy volunteers aged 18 to 50 years old from the USA. Each volunteer received one of three different doses of injected vaccine at weeks 0, 4, and 20. Chikungunya neutralising antibodies in the blood sera of recipients were measured at regular intervals.

Vaccinations were well tolerated with no serious adverse events reported, and no evidence of any inflammatory side effects. Four participants reported mild to moderate side effects related to the treatment; transient alanine aminotransferase increases (an enzyme present in liver and heart cells that is elevated when these organs are damaged) and transient neutropenia (low white blood cell count that leaves individuals vulnerable to infections.)

An immune response in the form of neutralising antibodies was detected in the majority of recipients after the first vaccination. Even the lowest doses of the vaccine were effective, and following the second vaccination, all recipients in all dose groups had developed high levels of antibodies. Importantly, antibodies were long-lasting and could be detected in all participants 6 months after their last vaccination.

Dr Ledgerwood explained, "Eleven months after vaccination, antibody levels were comparable to those seen in people who had recovered after natural chikungunya infection, suggesting that the VLP vaccine could provide long-term protection against the virus. The vaccine also generated antibodies against multiple genotypes of the virus, suggesting that it could be effective against any strains of the virus."*

She added, "Such a VLP vaccine should be relatively economical to produce in large quantities because it needs minimal containment as live virus is not required for production. This same approach could also be applied to the production of vaccines against a range of viruses related to chikungunya that cause encephalitis."*

Writing in a linked Comment, Dr Ann Powers from the Centers for Disease Control and Prevention in the USA said, "Although this VLP vaccine candidate exhibits a range of properties that suggest it would be a good vaccine option, there is always concern about whether a vaccine for a vector-borne virus will be licensed. Development of vaccines for orphan agents is challenging because the market might not be large enough to justify the investment. The cost of development of a vaccine—from preclinical studies to vaccine registration—is estimated to be US$200–500 million. Yet, even with this need for substantial funding, vaccines are still the most cost-effective strategy for disease prevention…In view of the burden of chikungunya outbreaks, which have affected up to 63% of local populations in a matter of months, the continued development of this VLP vaccine candidate, along with other vaccine options, should be encouraged."