CTH522 Chlamydia Vaccine
Statens Serum Institut (SSI) CTH522 Chlamydia vaccine candidate is a multi-component prime-boost Chlamydia trachomatis vaccination regime. The vaccine antigen CTH522 is a recombinant, engineered version of the C. trachomatis major outer membrane protein (MOMP), comprising heterologous immunorepeats from four genital C. trachomatis serovars (D, E, F, and G). Preclinical research on the CTH522 vaccine led to the selection of the liposome-based cationic adjuvant formulation CAF®01, designed to induce a strong cell-mediated immune response combined with antibody induction.
On February 23, 2024, Nature Communications published a report on a comparative immunological characterization of CTH522/CAF®01 in female mice and humans was published. We find a range of immune signatures that translate from mouse to human, including a Th1/Th17 cytokine profile and antibody functionality. We identify vac ine-induced T cell epitopes conserved among Chlamydia serovars and previously found in infected individuals. Using the mouse model, we show that the common immune signature protected against ascending infection in mice, and vaccine-induced antibodies could delay bacterial ascension to the oviduct and the development of pathology in a T cell-depleted mouse model. Finally, we demonstrate long-lasting immunity and protection of mice one year after vaccination.
A study funded by The EU Horizon Program TRACVAC at the National Institute for Health Research Imperial Clinical Research Facility, London, UK, reported on April 11, 2024, CTH522, adjuvanted with CAF01 or CAF09b, is safe and immunogenic, with 85 μg CTH522-CAF01 inducing robust serum IgG binding titers. Intradermal vaccination conferred systemic IgG neutralization breadth, and topical ocular administration increased ocular IgA formation. These findings indicate CTH522 vaccine regimens against ocular trachoma and urogenital chlamydia for testing in phase 2 clinical trials.
Statens Serum Institut (SSI) was inaugurated in September 1902 and is under the auspices of the Danish Ministry of Health. SSI has developed a unique vaccine strategy to combat this challenging infection. SSI envisions a vaccine that elicits cell-mediated and humoral immunity, with neutralizing antibodies as the primary role in reducing the initial infectious load. On the other hand, the bacteria are intracellular so that a bactericidal cell-mediated immune response will target them.
CTH522 Chlamydia Vaccine Dosage
During the recent phase 1 study, participants were randomly assigned (1:1:1:1:1) to each of the group's A–E (12 participants each), and six were randomly assigned to group F. Investigators were masked to treatment allocation. GGrupsA–E received an investigational medicinal product, and Group F received a placebo only. Tw liposomal adjuvants, CAF01, and CAF09b, were comp red. Th groups were intramuscular 85 μg CTH522-CAF01, or placebo on day 0 and two boosters or placebo at days 28 and 112, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (A); intramuscular 85 μg CTH522-CAF01, two boosters at day 28 and 112 with additional topical ocular administration of CTH522, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (B); intramuscular 85 μg CTH522-CAF01, two boosters at day 28 and 112 with additional intradermal administration of CTH522, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (C); intramuscular 15 μg CTH522-CAF01, two boosters at day 28 and 112, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (D); intramuscular 85 μg CTH522-CAF09b, two boosters at day 28 and 112, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (E); intramuscular placebo (F).
CTH522 Chlamydia Vaccine Indication
Chlamydia trachomatis is the most common sexually transmitted bacterial infection worldwide. An infection with the bacteria C. trachomatis causes chlamydia. The bacteria is like a virus, which relies on its host to survive and reply. Ate. C. trachoma tis has two developmental forms: a small (0.3 microns) non-replicating infectious form which, after attachment, is internalized into the host cell and instantly reorganized into a metabolically active and replicating form of almost triple the size. After completing a replicative cycle, it reorganizes into the infectious form and is released from the host cell. If the immune system does not control the bacteria, it may ascend to infect the fallopian tubes and cause significant damage, leading to pelvic inflammatory disease, scarring, and occlusion.
CTH522 Chlamydia Vaccine News
April 11, 2024 - Editorial: Immunological responses in a Chlamydia trachomatis vaccine trial.
November 22, 2022 - The Frontiers Immunology published an ORIGINAL RESEARCH article - This study evaluated the immunogenicity and protective efficacy of combined multi-component immunization strategies with both protein vaccines (CTH522, Con E), DNA vaccine and recombinant viral vector (MVA-MOMP), and adeno vector-based vaccines, in a non-human primate (NHP) model.
August 12, 2019 - The Lancet Infectious Diseases - Safety and immunogenicity of the chlamydia vaccine candidate CTH522 adjuvanted with CAF01 liposomes or aluminum hydroxide: a first-in-human, randomized, double-blind, placebo-controlled, phase 1 trial.
CTH522 Chlamydia Vaccine Clinical Trials
NCT03926728: A Phase I, Double-blind, Parallel, Randomised and Placebo-controlled Trial (CHLM-02) Investigating the Safety and Immunogenicity of a Chlamydia Vaccine, CTH522, in Healthy Ad ts. Biologica CTH522-CAF01 IM; CTH522-CAF09b IM; CTH52 ID. Findings: Between February 17, 2020 and February 22, 2022, of 154 participants screened, 65 were randomly assigned, and 60 completed the trial (34 [52%] of 65 women, 46 [71%] of 65 White, mean age 26·8 ye rs). No serious adverse events occurred, but one participant in group A2 discontinued dosing after having self-limiting adverse events after both placebo and investigational medicinal products did. Study procedures were otherwise well tolerated; most adverse events were mild to moderate, with only seven (1%) of 865 reported as grade 3 (sev re). There was a 100% four-fold seroconversion rate by day 42 in the active groups (A–E) and no seroconversion in the placebo group. Serum IgG-CTH522 titers were higher after 85 μg CTH522-CAF01 than 15 μg, although not significantly (intention-to-treat median IgG titer ratio groups A–C: D=5·6; p=0·062), with no difference after three injections of 85 μg CTH522-CAF01 compared with CTH522-CAF09b (group E). IIntradermal TH522 (group C) induced high titers of serum IgG anti-CTH522 neutralizing antibodies against serovars B (trachoma) and D (urogeni al). Topical ooclarCTH522 (group B) at days 28 and 112 induced higher total ocular IgA compared with baseline (p<0· 01). Participants in all active vaccine groups, particularly groups B and E, developed cell-mediated immune responses against CTH522.
NCT02787109: Findings: Between August 15, 2016, and February 13, 2017, 35 women were randomly assigned (15 to CTH522:CAF01, 15 to CTH522:AH, and five to plac bo). 32 (91%) received all five vaccinations, and all participants were included in the intention-to-treat anal sex. No related serious adverse reactions were reported, and the most frequent adverse events were mild local injection-site reactions, which were reported in all (15 [100%] of 15) participants in the two vaccine groups and three (60%) of five participants in the placebo group (p=0·0526 for both companies ns). Intranasal vaccination was not associated with a higher frequency of related local reactions (reported in seven [47%] of 15 participants in the active treatment groups vs three [60%] of five in the placebo group; p=1· 00). CTH522:CAF 1 and CTH522:AH induced anti-CTH522 IgG seroconversion in 15 (100%) of 15 participants after five immunizations, whereas no participants in the placebo group were seroconve ted. CTH522:CAF 1 showed accelerated seroconversion, increased IgG titers, an enhanced mucosal antibody profile, and a more consistent cell-mediated immune response profile than CTH522:AH.
