female Aedes aegypti mosquito
August 18, 2014

Experimental Vaccine Against Chikungunya Induces Robust Antibody Response

April Flowers for redOrbit.com - Your Universe Online

As if West Nile virus and malaria weren't enough, mosquitoes are now delivering the chikungunya virus, which was first identified in the early 1950s in East Africa. The virus, characterized by severe joint pain, headache and fever, has caused sporadic outbreaks in Africa, India and Thailand throughout the 1960s and 1970s. Now, as of 2013, it has reached the Western Hemisphere and there are no vaccines or specific drug treatments to deal with it.

"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.

As of August 8 of this year, upwards of 570,000 confirmed or suspected cases have been reported throughout the Americas - 484 of those in the continental US. The good news, as reported in The Lancet, is that scientists believe they have a vaccine. Researchers from the National Institute of Allergy and Infectious Diseases (NIAID) say that their experimental vaccine elicited neutralizing antibodies from all 25 adult volunteers participating in an early-stage clinical trial.

"The two species of mosquito that spread chikungunya virus are found in parts of the continental United States, so it may just be a matter of time before this illness gains a foothold here," said NIAID Director Anthony S. Fauci, M.D. "Therefore, it is prudent to begin addressing this emerging public health threat with the development of vaccines, such as this one, which was designed and tested by scientists from the NIAID Vaccine Research Center."

Non-human primates were tested in 2010 by the Vaccine Research Center (VRC), with all immunized animals being protected from infection when exposed to the virus.

In the clinical human trial lasting 20 weeks, 23 healthy volunteers received three injections, while the remaining two participants received two injections of the vaccine at differing dosages of 10, 20, or 40 micrograms. Antibody production was measured multiple times following each injection, and chikungunya neutralizing antibodies were detected after the second shot in all participants. A significant boost in antibodies was noticed after the third injection. All of the participants, even those who received the lowest dosage, exhibited vaccine-induced antibodies for at least 11 months after the trial. This indicates that the vaccine could provide durable protection.

"The candidate vaccine prompted a robust immunological response in recipients and was very well tolerated," noted Ledgerwood. "Notably, the levels of neutralizing antibody produced in response to the experimental vaccine were comparable to those seen in two patients who had recovered from a chikungunya virus infection acquired elsewhere. This observation gives us additional confidence that this vaccine would provide as much protection as natural infection."

The new vaccine is different from most typical vaccines because, rather than being made from killed viruses or weakened live viruses, this one is created from a virus-like particle (VLP) developed from the outer structural proteins of the West African strain 37997. Vaccines created from VLPs usually prompt an immune system reaction similar to that of natural, whole virus exposure. Dr. Ledgerwood said that VLP vaccines have many advantages over traditional vaccines. VLP vaccines do not need to be produced in a high-level biocontainment facility, for example, because no live viruses are used in the manufacturing process.

Ledgerwood 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."

There was no substance added to the vaccine to improve the immune system response, known as an adjuvant. Formulating the new vaccine with an adjuvant might make it possible to achieve similar immune responses with lower dosages.

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 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."


Chikungunya: Webster's Timeline History, 1957 - 2007 by Icon Group International