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An investigational vaccine against chlamydia (CTH522) induced neutralizing antibodies in all participants who received it, and with no major safety concerns, results of a phase I trial showed.

A 100% fourfold seroconversion rate occurred in all groups receiving CTH522, a recombinant vaccine containing the major outer membrane of Chlamydia trachomatis, with no seroconversion in placebo recipients, reported Katrina Pollock, PhD, of Imperial College London, and colleagues.

"The present study is the second clinical trial of a vaccine with immunogenicity against trachoma and urogenital chlamydia serovars, and the first to assess ocular immune responses of a vaccine against C. trachomatis since the trachoma trials in the 20th century," they wrote in . Aside from one clinical trial for a chlamydia vaccine in 2019, the authors said they turned up only six references to trials conducted in four countries between 1966 to 1979.

In the current study, 59 of the 65 participants were randomly assigned to five groups of the intramuscular vaccine (groups A-E, with an 85-μg dose for four groups and a 15-μg dose for one group) along with one of two liposomal adjuvants (CAF01 or CAF09). Six participants received placebo only (group F). The six groups were further divided into 12 and assigned to one of three booster approaches (intramuscular with liposomal adjuvant, intradermal without adjuvant, and topical ocular without adjuvant) or placebo at days 28, 112, and 140.

The findings of this trial are "compelling," said Wilhelmina Huston, PhD, of the University of Technology in Sydney, in an . "A vaccine against chlamydia is widely agreed to be an essential public health control measure for both sexually transmitted and ocular infections."

"It is promising to see that the ocular IgA against the vaccine antigen was significantly enhanced by topical ocular vaccination or boosting regimens, particularly, in the group who received two topical ocular boosts after the initial intramuscular prime," though ocular antibodies did not differ based on doses, Huston noted.

Most participants were white (71%), nearly half were men (48%), and they were an average age of 26.

The primary outcome was safety in terms of local injection site reactions, local ocular reactions, and systemic reactions after any injections. The secondary outcome was humoral immunogenicity of anti-CTH522 IgG seroconversion as a fourfold or 10-fold increase over baseline. Five patients withdrew, leaving 60 participants who completed the trial.

No serious adverse events (AEs) or deaths occurred, and no participants withdrew due to AEs.

After the initial intramuscular shot, nearly all vaccine participants reported injection site reactions, most commonly pain (97%), warmth (27%), and swelling (10%). About one in five also had systemic reactions, including myalgia in 15%, chills in 10%, and pyrexia and rash in 3% each. Injection pain and warmth were each reported by one of the six placebo recipients. Injection site reactions after the second and third shots were common as well for vaccine participants.

Most participants also reported ocular reactions after the topical vaccine or placebo, with no significant differences among participants. The most commonly reported effect was discomfort (19% and 17%, respectively), with a handful of reports of redness (13% and 17%), tearing up (9% and 33%), or eyelid swelling (6% and 0%).

Intramuscular injections were discontinued in one participant who experienced vomiting and headache after the second dose (day 26). That patient received ocular vaccination on day 105 and reported headache, vomiting, and watery eyes afterward.

All trial participants who received the active vaccine seroconverted after the second dose and maintained seroconversion through the end of the trial. Titers were five to six times higher in participants randomized to 85 μg CTH522-CAF01 compared to 15 μg CTH522-CAF01, but the difference was not significant. No significant differences occurred among those receiving the CAF01 adjuvant versus the CAF09 adjuvant either.

Titers were higher in the participants who received an intradermal vaccine at day 126 compared to those who received the topical ocular vaccine, which was significant in one group.

Memory B cell responses based on ELISpot were significant in all participants who received the active vaccine, peaking at days 140 and 154 and returning to baseline by day 238.

Ocular IgG concentrations were significantly higher than baseline in all active vaccine groups except one, with no notable differences between those receiving the topical versus intradermal boosters at the first booster dosing.

"Conversely, ocular anti-CTH522 IgA concentrations were significantly higher than baseline following topical ocular vaccinations for group B from day 126 (2 weeks after the third vaccination) onwards," the authors reported (P=0.005). "Ocular IgA concentrations were consistently higher following topical ocular CTH522 administration in group B when compared with all other groups."

Group B's protocol was three intramuscular vaccinations of 85 μg CTH522-CAF01, with a split into two groups after the initial vaccination: One received 12 μg topical ocular vaccination of the unadjuvanted CTH522 at days 28 and 112, and topical ocular placebo at day 140, and the other received the same for days 28 and 112, and unadjuvanted topical ocular CTH522 at day 140. All ocular doses were given in each eye.

No significant differences in seroconversion occurred between sexes, though they were not evenly distributed across the groups.

Statistical analyses, including between-group comparisons, were limited by the small sample size, according to the study authors.

But "tantalizing insights were gained that might inform future chlamydial vaccine trials," Huston wrote. "Dosing regimens that cover multiple administration rounds are influential on the outcomes, and it will be worth investing up front in distinctive dosing and administration groups in future studies (at larger scale)."

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