CHIKV-VLP Chikungunya Vaccine Clinical Trials, Dosage, Efficacy, Indication, Side Effects
Bavarian Nordic A/S chikungunya adjuvanted CHIKV-VLP vaccine candidate (PXVX0317) is a single dose aluminum hydroxide-adjuvanted chikungunya virus-like particle vaccine (VLP) with a multi-protein structure that mimics the organization and conformation of naturally occurring viruses without the viral genome, promoting a more robust immune response and increased antibody production. Studies have shown that VLP vaccines are highly immunogenic, have a proven safety record, and typically elicit high titer-neutralizing antibodies needed to protect against the chikungunya virus (CHIKV). The CHIKV VLP vaccine candidate is licensed from the U.S. National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH).
On June 26, 2024, Bavarian Nordic A/S announced the submission of a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) seeking approval of the Company’s vaccine candidate. As of July 18, 2024, the EMA had validated the MAA. The MAA application was granted accelerated assessment by the EMA's Committee for Medicinal Products for Human Use in February 2024, supporting the potential approval of the vaccine by the European Commission in the first half of 2025. The EMA granted PRIME designation in January 2020 (EMEA-002656-PIP01-19).
On August 13, 2024, Bavarian Nordic announced that the U.S. Food and Drug Administration (FDA) had accepted and granted a Priority Review and Fast Track for the Biologics License Application for CHIKV VLP for individuals 12 and older. The FDA posted the Briefing Document on November 8, 2019. The FDA assigned a Prescription Drug User Free Act target action date of February 14, 2025. If approved, CHIKV VLP will be the first and only VLP single-dose chikungunya vaccine approved in the U.S. for persons 12 years of age and older. Dr. Victoria Jenkins presented phase 3 clinical trial safety and efficacy data on CHIKV VLP at the Advisory Committee on Immunization Practices meeting on October 23, 2024.
Bavarian Nordic A/S is a fully integrated vaccine company focused on developing, manufacturing, and commercializing life-saving vaccines, with an office in Denmark. Gaithersburg, Maryland-based Emergent BioSolutions sold this vaccine to Bavarian Nordic A/S on May 15, 2023.
CHIKV-VLP Chikungunya Vaccine Indication
The CHIKV-VLP vaccine candidate is indicated to prevent infections of the chikungunya virus. The Chikungunya virus is spread to people through infected mosquitoes. Symptoms lasting 3-4 weeks include high-grade fever, joint pain, headache, muscle pain, joint swelling, or rash, while chronic arthritis occurs in a minority of patients.
CHIKV-VLP Chikungunya Vaccine Dosage
In clinical trials, the CHIKV-VLP vaccine candidate is administered as a 40 µg dose muscular injection.
CHIKV-VLP Chikungunya Vaccine Side Effects
The most common solicited adverse event in a phase 2 study was pain at the injection site, reported in 12 (23%) of 53 participants who received the unadjuvanted vaccine (group 1) and 111 (31%) of 356 who received the adjuvanted vaccine. No vaccine-related serious adverse events were reported.
Chikungunya Cases
Since 2014, the U.S. CDC has reported chikungunya virus disease cases among U.S. travelers returning from affected countries in the Region of the Americas. As of October 2024, there have been chikungunya outbreaks in numerous countries.
CHIKV-VLP Chikungunya Vaccine News
August 13, 2024 - “The FDA review, along with the ongoing review of our CHIKV VLP vaccine by EMA, represent the first regulatory reviews of a chikungunya vaccine for adolescents, potentially providing a broader usage by populations at risk of this debilitating disease,” commented Paul Chaplin, President and CEO of Bavarian Nordic.
July 18, 2024 - “The MAA submission and review marks a pivotal milestone for Bavarian Nordic in 2024, and we look forward to working closely with EMA throughout the evaluation process to make our chikungunya vaccine available to individuals 12 years of age and older at risk of chikungunya virus infection,” said Paul Chaplin, President and CEO of Bavarian Nordic.
June 26, 2024 - “The MAA marks our second major submission in just a few weeks as part of our efforts to launch the chikungunya vaccine next year in the U.S. and Europe,” said Paul Chaplin, President and CEO of Bavarian Nordic, in a press release.
May 15, 2023 - Bavarian Nordic acquired the rights to the development-stage chikungunya vaccine candidate CHIKV VLP. Bavarian Nordic also acquired manufacturing facilities in Bern, Switzerland, and development facilities in San Diego, California.
November 1, 2022 - Emergent BioSolutions Inc. announced results from a Phase 2 study evaluating the safety and immunogenicity of the CHIKV VLP vaccine candidate in prior recipients of other investigational alphavirus vaccines. The study demonstrated that the CHIKV VLP vaccine candidate was well-tolerated and immunogenic in alphavirus vaccine-naïve participants and participants previously vaccinated against the Venezuelan equine encephalitis virus.
May 26, 2021 - Emergent BioSolutions Inc. announced two-year persistence data from its Phase 2 clinical study. Two years post-vaccination, SNA responses were 19 times higher than pre-vaccination titers following a single adjuvanted 40 µg dose of the CHIKV VLP vaccine, supporting the persistence of the immune response. All subjects in the single-dose regimen remained seropositive at their one-year and two-year visits. The vaccine candidate was well-tolerated, and no significant vaccine-related safety concerns were identified.
January 13, 2020 - Emergent BioSolutions Inc. announced that it had received an agreement from the European Medicines Agency to pursue its proposed development plan for its chikungunya virus virus-like particle (CHIKV VLP) vaccine candidate.
April 26, 2019 - Study published by PLOS: Vaccination with a chikungunya virus-like particle vaccine exacerbates disease in aged mice. Conclusions: Unadjuvanted CHIK VLP vaccination elicits immune responses that protect 100% of adult mice against CHIKV infection. However, an improved vaccine/adjuvant combination is still necessary to enhance the protective immunity against CHIKV in older people.
January 28, 2021 - A VLP vaccine for the epidemic Chikungunya virus protects non-human primates against infection.
CHIKV-VLP Clinical Trials
The CHIKV-VLP vaccine candidate is being investigated in phase 3 clinical trials (clinicaltrials.gov i identifiers NCT05072080 and NCT05349617).
According to a study presented in October 2023, the researchers assessed anti-CHIKV serum-neutralizing antibody titers at designated time points throughout the study. They determined the seroresponse rate (SRR) in the two cohorts. In total, 3,254 participants were enrolled in the adult/adolescent trial, of whom 2,790 received a dose of CHIKV VLP, and 464 received a placebo. The data showed an SRR of 98% on day 22 for the vaccine and 1% for placebo. A rapid antibody response was also observed in the vaccine group, with an SRR of 47% on day 8 and 97% on day 15. These responses were""durable"" through day 183, when the SRR was 86%. For the older adult trial, 413 participants were enrolled — 206 received CHIKV VLP, and 207 received a placebo. On day 22, the SRR was 87% for vaccine recipients and 1% for placebo recipients. By day 15, a rapid antibody response was also observed in the CHIKV VLP group, with an SRR of 82%. Additional data from the study showed that the vaccine had a favorable safety profile, with most adverse events being mild to moderate, the most common of which were myalgia, fatigue, and headache.
On June 20, 2023, the Company announced phase 3 study results: 413 participants were enrolled and randomized 1:1 to receive either a single intramuscular injection of CHIKV VLP or a placebo. The initial results up to Day 22 post-vaccination showed that CHIKV VLP was immunogenic in healthy adults ≥65 years of age, as demonstrated by a strong induction of CHIKV neutralizing antibodies in 87% of vaccinees with neutralizing antibody titers exceeding the threshold agreed with authorities as a marker of seroprotection, thus meeting the primary endpoints of the study. Notably, most subjects (82%) were also observed seroprotective neutralizing antibodies on Day 15 post the single vaccination, demonstrating a fast onset of protection for the VLP-based CHIKV vaccine candidate.
On August 6, 2023, Bavarian Nordic (B.N.) announced positive topline results from a Phase 3 clinical trial (NCT05072080); PXVX0317 met all the co-primary endpoints and was shown to be highly immunogenic in the majority of subjects 22 days following a single vaccination. A fast and durable response was confirmed with high immunity levels at two weeks and six months post-immunization.
On November 14, 2022, the Company announced a planned post-approval multicenter Phase 3b clinical study will evaluate the vaccine candidate's efficacy in preventing CHIKV disease and assess the utility of a model-guided disease surveillance framework to optimize the execution of a field efficacy trial using CHIKV as a model emerging pathogen.
On Nov. 1, 2022, the Company reported a Phase 2 parallel group- a gender-matched, open-label study evaluating the safety and immunogenicity of an adjuvanted CHIKV VLP vaccine candidate in prior recipients of experimental alphavirus vaccines in comparison to a cohort of alphavirus vaccine-naïve individuals, enrolled 60 healthy adults at two U.S. sites. The vaccine candidate was well-tolerated, with no notable difference in the incidence of adverse events between the groups. The majority of solicited adverse events were mild or moderate. The most common adverse event was local injection site pain. The seroconversion rate 21 days post-vaccination was 100% in both groups. A higher percentage of prior alphavirus vaccine candidate recipients rose four-fold on study day eight, tightening the alphavirus vaccine-naïve group.
The randomized, double-blind, parallel-group, phase 2 study was conducted at three U.S. sites with 445 participants. Eligible participants were healthy CHIKV-naïve adults aged 18–45 years. The primary endpoint was the geometric mean titer of the anti-CHIKV neutralizing antibody on day 57 (28 days after the last vaccination). Safety was also assessed.