番茄社区

BOSTON -- Vaccine candidates for chikungunya virus and for the ubiquitous cytomegalovirus performed well in human clinical trials, researchers reported here at the annual IDWeek meeting.

In two phase III trials, the adjuvanted chikungunya virus vaccine achieved its primary and key secondary endpoints in healthy participants 12 years of age and older, reported Jason Richardson, PhD, clinical director of research for vaccine developer Bavarian Nordic in Toronto.

The recombinant virus-like particle vaccine is administered intramuscularly with a single microgram dose of 0.8 mL, which is delivered in a pre-filled syringe and is adjuvanted with aluminum hydroxide.

Chikungunya virus is spread to people by the bite of an infected mosquito. The most common symptoms of infection are fever and joint pain. Other symptoms may include headache, muscle pain, joint swelling, or rash. Outbreaks have occurred in countries in Africa, the Americas, Asia, and Europe, and in the Caribbean and island nations in the Indian and Pacific oceans as well, and there is a risk the virus will be spread to unaffected areas by infected travelers.

"There is no licensed vaccine available to prevent disease. Treatment focuses on alleviating the associated symptoms," Richardson said.

Chikungunya Virus Vaccine Trials

The first trial, EBSI-CV-317-004, was aimed at showing safety, immunogenicity, and lot-consistency of the vaccine that was delivered to a total of 3,258 healthy adults and children. Participants were randomized to receive one of three lots of the vaccine or placebo injections. The 6-month study enrolled participants ages 12 to less than 65 years of age at 47 centers in the U.S.

Overall, 97.8% of the individuals in the trial achieved anti-chikungunya virus serum neutralizing antibodies by day 22 after administration compared with 1% of people who received placebo (P<0.0001), meeting the predefined success criterion.

An antibody titer that would confer presumptive seroprotection was seen in 86% and 47% of vaccine recipients at day 8 and at day 183, respectively. In the placebo group, the corresponding response rates were 1.5% and 0.5%, respectively. Geometric mean titer and lot consistency endpoints were also met.

In the second trial, EBSI-317-005, 413 individuals were randomized to receive the chikungunya vaccine candidate or placebo and followed for 6 months at 10 sites in the U.S.

Richardson reported that 87.3% of the vaccine group demonstrated a statistically significant seroresponse rate at day 22, compared with 1.1% of the placebo group. The vaccine group geometric mean titer was significantly higher than that of placebo at day 22 (724 vs 8, P<0.0001).

"All primary and key secondary endpoints were met for both phase III studies in healthy participants 12 years of age and older," Richardson said. "The immune response to the vaccine was rapid and robust, demonstrating an increase in anti-chikungunya seroresponse rate and geometric mean titer over time."

He said that the vaccine was well-tolerated in both studies, with no treatment-related serious adverse events. Most solicited and unsolicited adverse events were mild or moderate in intensity, Richardson said.

While the chikungunya vaccine appeared to produce neutralizing antibodies adequate to prevent infection, "doing clinical efficacy trials in these areas would be difficult," session co-moderator Satoshi Kamidani, MD, PhD, of Emory University School of Medicine in Atlanta, told 番茄社区.

Cytomegalovirus Vaccine

Researchers demonstrated in a phase II study that an mRNA vaccine candidate produced responses in patients who had documented infection with cytomegalovirus and in individuals who were free of infection with the pathogen, which is a widespread latent virus considered the leading infectious cause of birth defects globally and a substantial cause of morbidity in immunocompromised individuals.

"There are no approved vaccines available, and a safe and effective method for the prevention of cytomegalovirus infection is a public health priority," said Sandeep Basnet, MD, director of clinical development at Moderna in Cambridge, Massachusetts.

The phase II trial, reported in the same late-breaker session as the chikungunya data, enrolled 89 individuals who were positive for cytomegalovirus and 205 individuals who were cytomegalovirus seronegative. Basnet said mRNA-1647 was generally well-tolerated at all dose levels assessed -- 50, 100, and 150 µg -- regardless of baseline cytomegalovirus serostatus.

Among seronegative participants, neutralizing antibodies against epithelial cell infection and against fibroblast infection increased after doses one, two, and three of mRNA-1647. Neutralizing antibodies against epithelial cell infection were above the seropositive benchmark through the end of the trial.

Among seropositive participants, neutralizing antibodies against epithelial cell infection and against fibroblast infection increased after dose one of mRNA-1647 only.

T-cell responses following mRNA-1647 were maintained through day 504.

Basnet said that the 100-µg dose of mRNA-1647 was selected for phase III trials, with in healthy individuals ages 16 to 40.

In commenting on the studies, Kamidani noted that pediatric studies are also planned, "so we can immunize children before they become adults and become pregnant, and in turn, prevent congenital infections. It seems that they are moving ahead with this vaccine candidate."