An oral vaccine against Chlamydia trachomatis

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Principal Investigator: GUANGMING  ZHONG
Organization: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
Fiscal Year: 2024
Award: $2,202,675
Funding agency: National Institute of Allergy and Infectious Diseases

Abstract
This proposal is to produce IND-enabling data for supporting clinical trials of an attenuated clone
of the mouse-adapted Chlamydia muridarum (CM) as a novel oral vaccine known as intrOv for
protecting humans from sexually transmitted infection with Chlamydia trachomatis (CT).
Extensive searching for a subunit vaccine against CT has not produced a licensed vaccine. One
of the challenges is that all 8 STI-causing CT serovars (D to K) are significant human pathogens
globally. We are proposing to develop intrOv into an oral vaccine against 8 CT serovars. Following
a single oral inoculation, CM can establish long-lasting colonization in the mouse gastrointestinal
(GI) tract but without causing any significant pathologies; Oral CM induces Th1-dominant
transmucosal immunity against subsequent infection in the genital tract and airway but without
altering CM colonization in the GI tract; CM colonization in the GI tract for 1 week is sufficient for
inducing protective immunity in the genital tract and antibiotics clearance of GI tract CM does not
compromise the genital protective immunity; To improve the safety of CM as an oral vaccine,
genital tract pathogenicity-attenuated CM clones have been generated by various labs but the
clone designated as intracellular Oral vaccine vector or intrOv is particularly attractive since it is
still able to induce transmucosal protection in the genital tract but no longer maintains long-lasting
colonization in the colon; IntrOv induces IFN+ILC3s and is also inhibited by IFN+ILC3s; Finally
intrOv-induced transmucosal immunity conferred cross-species protection against CT in the
genital tract, validating previously observed CM induction of anti-CT immunity. Thus, we
hypothesize that oral intrOv protects human genital tract from CT infection and the intrOv-induced
IFN+ILC3s in the gut may present cross-species epitopes to lymphocytes for mediating Th1-
dorminant transmucosal immunity. We will test these hypotheses by validating the protection
efficacy of intrOv against genital CT in mice and large animals, identifying protective correlates
and CT antigens for improving clinical assays & intrOv efficacy and improving the quality and
safety of intrOv as a human oral vaccine. Our hypotheses are consistent with these successful
examples of using animal-adapted microbes to protect against human pathogens: cowpox as a
vaccine against smallpox, BCG (M. bovis) against M. tuberculosis and meningococcal vaccine
against gonorrhoea.

Terms: <Address><Alimentary Canal><Animals><Antibiotic Agents><Antibiotic Drugs><Antibiotic Therapy><Antibiotic Treatment><Antibiotics><Antigen-Presenting Cells><Antigenic Determinants><Antigens><Assay><Attenuated><Attenuated Live Virus Vaccine><Attenuated Live viral Vaccine><Attenuated Vaccines><Binding Determinants><Bioassay><Biological Assay><Biotech><Biotechnology><C muridarum><C psittaci><C trachomatis><C. muridarum><C. psittaci><C. trachomatis><CD4 Cells><CD4 Positive T Lymphocytes><CD4 T cells><CD4 helper T cell><CD4 lymphocyte><CD4+ T-Lymphocyte><CD4-Positive Lymphocytes><Cannot achieve a pregnancy><Cell Body><Cells><Cervicitis><Chlamydia Infections><Chlamydia muridarum><Chlamydia psittaci><Chlamydia trachomatis><Chlamydial Infection><Chlamydophila psittaci><Clinical><Clinical Evaluation><Clinical Testing><Clinical Trials><Colon><Cow Pox><Cowpox><Cross Presentation><Cross Reactions><Data><Difficulty conceiving><Digestive Tract><Disease><Disorder><Epitopes><Evaluation><FDA approved><Formulation><Future><GI Tract><Gastrointestinal Tract><Gastrointestinal tract structure><Genital Organs><Genitalia><Gonococcal Infection><Gonorrhea><Human><Hydrogen Oxide><Immune response><Immune system><Immunity><Immunological response><Infection><Infertility><Legal patent><Letters><Licensing><Link><Live-attenuated Vaccine><Lymphatic cell><Lymphocyte><Lymphocytic><Lymphoid Cell><M bovis><M tb><M tuberculosis><M. bovis><M. tb><M. tuberculosis><MTB vaccine><Mediating><Meningococcal vaccine><Mice><Mice Mammals><Microbe><Miscellaneous Antibiotic><Modern Man><Monitor><Monkeys><Mouse Strains><Mucosa><Mucosal Immunity><Mucosal Tissue><Mucous Membrane><Murine><Mus><Mycobacterium bovis><Mycobacterium tuberculosis><Mycobacterium tuberculosis var. bovis><Oral><Patents><Pathogenicity><Pathology><Phenotype><Pre IND FDA meeting><Pre-IND mtg><Predisposition><Production><RNA vaccine><RNA-based vaccine><Reporting><Rickettsia trachomae><Safety><Sexually Transmitted Diseases><Sexually Transmitted Disorder><Sexually Transmitted Infection><Smallpox><Subunit Vaccines><Susceptibility><T4 Cells><T4 Lymphocytes><TB vaccine><Testing><Texas><Toxicology><Tuberculosis Vaccines><Universities><Vaccine for TB><Vaccine for Tuberculosis><Vaccines><Variola><Venereal Diseases><Venereal Disorders><Venereal Infections><Water><accessory cell><alimentary tract><anti-TB vaccine><attenuate><attenuates><bacterial disease treatment><bacterial infectious disease treatment><chlamydial disease><clinical test><digestive canal><experience><experiment><experimental research><experimental study><experiments><fertility cessation><fertility loss><genital tract><host response><human pathogen><immune system response><immunogen><immunoresponse><improved><infertile><live vaccine><live vaccines><lymph cell><mRNA vaccine><mRNA-based vaccine><male><mtb><novel><oral vaccine><phase 1 trial><phase I trial><plasmid vaccine><pre-IND consultation><pre-IND discussion><pre-IND meeting><pre-Investigational New Drug meeting><prevent><preventing><recruit><reproductive tract><research clinical testing><sexually acquired infection><small pox><trachoma vaccine><vaccine against M. tuberculosis><vaccine against Mtb><vaccine against Mycobacterium tuberculosis><vaccine against TB><vaccine against tuberculosis><vaccine candidates against tuberculosis><vaccine efficacy><variola major><vector vaccine><yaba>