Developing a Single-shot Vaccine Against Chikungunya
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Chikungunya is a viral disease which can be transmitted via the bite of a mosquito infected with the chikungunya virus (CHIKV). Currently there is no preventative vaccine approved for use, and travelers visiting countries with CHIKV are advised to protect themselves by preventing mosquito bites.
We recently spoke with Thomas Lingelbach, CEO at Valneva to learn more about the development of the company's chikungunya vaccine candidate and the results of their recent Phase 1 clinical study.
Laura Lansdowne (LL): For readers less familiar with Valneva, could you tell us a little about the company?
Thomas Lingelbach (TL): Valneva is a biotech company developing and commercializing vaccines for infectious diseases with major unmet medical needs.
Valneva’s portfolio includes two commercial vaccines for travelers: IXIARO®/JESPECT® indicated for the prevention of Japanese encephalitis and DUKORAL® indicated for the prevention of cholera and, in some countries, prevention of diarrhea caused by ETEC, the most common cause of diarrhea in travelers.
Valneva also has a focused pipeline of vaccines in development against infectious diseases including a preventative vaccine against Lyme disease and a unique chikungunya vaccine program which has a potential single-shot long-term efficacy.
LL: You recently announced positive results for your chikungunya vaccine candidate. What is Chikungunya and what motivated the development of a vaccine for this disease?
TL: Chikungunya is a mosquito-borne viral disease caused by the chikungunya virus (CHIKV), a Togaviridae virus, transmitted by Aedes mosquitoes. The chikungunya virus causes illness in 72–92% of infected humans around four to seven days after being bitten by an infected mosquito. People infected with chikungunya may suffer from acute onset of fever, debilitating joint and muscle pain, headache, nausea and rash. These symptoms may potentially develop into long-term, serious health impairments such as visual, neurological, heart and gastrointestinal manifestations that in some extreme cases can lead to fatalities.
Chikungunya outbreaks have been reported in Asia, Africa, the Americas and Europe. As of 2017, there have been more than one million reported cases in the Americas. The medical burden is expected to grow as the CHIKV primary mosquito vectors continue to spread geographically.
Currently there are no preventive vaccines against chikungunya, making it a major threat to public health. We set out to develop VLA1553, a live-attenuated vaccine candidate, as a potential solution to the expanding health threat chikungunya poses. Our hope is that a preventative vaccine available for chikungunya will allow people living in and travelling to endemic areas to have peace of mind while enjoying the outdoors.
LL: Could you tell us more about the vaccine candidate VLA1553?
TL: VLA1553 is a monovalent, single dose, live-attenuated vaccine candidate aiming for protection against various chikungunya virus outbreak phylogroups and strains designed for long-lasting protection in adults and children. The target populations for vaccines against chikungunya are travelers, military personnel or individuals at risk who live in endemic regions. VLA1553 has been awarded Fast Track Designation by the U.S. Food and Drug Administration (FDA).
LL: Could you tell us more about the design of the study, objectives and the key findings?
TL: The study is a randomized, observer-blinded, multicenter, dose-escalation Phase 1 clinical study investigating three dose levels of VLA1553 after a single immunization. The study enrolled 120 healthy volunteers, 18 to 45 years of age, in the U.S. All 120 subjects were randomized in three different study groups to receive one of three dose levels (30 subjects in the low- and medium- and 60 subjects in the high-dose group). The protocol includes a re-vaccination at Month 6 or Month 12 to confirm that a single vaccination will be sufficient to induce high titer neutralizing antibodies and protect subjects from chikungunya viremia (intrinsic viral challenge). Study participants will be followed up until 13 months after initial vaccination and an independent Drug Safety Monitoring Board (DSMB) continuously oversees the study and reviews data.
The objectives of VLA1553-101 Phase 1 study are to assess the overall safety and immunogenicity profile after a single vaccination across three dose levels. The most recent analysis (Part B) of the ongoing study, released in May, included the overall safety and immunogenicity results up to Month 7, unblinded on a group level and including first results from the “intrinsic human viral challenge.
This most recent analysis showed that VLA1553 was generally safe in all dose groups. The low and medium dose groups were well tolerated and showed a superior safety profile, including viremia, compared to the high dose. No adverse events of special interest (e.g. chikungunya infection related) were reported up to Month 7 and the product candidate´s local tolerability profile was excellent.
Overall, the results showed an excellent immunogenicity profile in all vaccinated dose groups after a single vaccination with a 100% seroconversion achieved at Day 14 after a single vaccination in all dose groups and fully sustained at 100% at Month 6.
LL: Is there any further information you can share regarding the clinical development of VLA1553?
TL: Valneva is committed to advancing its chikungunya vaccine candidate as quickly as possible and expects to be in a position to announce a plan, agreed with regulators, to licensure for its FDA fast tracked candidate VLA1553 at its planned R&D investor day, July 9th in New York City.
LL: Are there any other vaccine candidates currently in the development pipeline that you would like to highlight?
TL: Our pipeline includes multiple vaccines in development including a unique vaccine against Lyme disease. Our Lyme vaccine candidate, VLA15, is designed to protect people against the six most common subtypes of Lyme disease and has the potential to be the only European Medicines Agency (EMA)/FDA-approved vaccine on the market that can prevent Lyme disease transmission to humans. Currently there is no vaccine available to protect humans against Lyme disease, the most common tick-borne disease in the Northern Hemisphere, and there is significant unmet need for a vaccine as the disease footprint widens. VLA15 is currently being tested in a Phase 2 clinical study to determine the optimal dose and schedule.
In addition to our robust R&D pipeline, we already have two very successful vaccines on the market: IXIARO®, for the prevention of Japanese Encephalitis, and DUKORAL®, approved for the prevention of cholera and, in some countries, for enterotoxigenic Escherichia coli (ETEC), the most common cause of traveler's diarrhea. Our successful commercial business continues to grow and helps fund the company’s various vaccines in development.