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Principal Investigator: Matthew Adrian Coleman
Organization: UNIVERSITY OF CALIF-LAWRNC LVRMR NAT LAB
Fiscal Year: 2021
Award: $383,595
Funding agency: National Institute of Allergy and Infectious Diseases
ABSTRACT
Throughout the world Chlamydia trachomatis (Ct) is the most common sexually transmitted bacterial
pathogen. In countries with poor sanitary conditions ocular infections with Ct can result in trachoma, the most
frequent cause of preventable blindness worldwide. Based on protection and serological studies in mice Ct is
classified into 15 major serovars of which eight account for most of the sexually transmitted infections (STI). In
men and women, the majority of genital Ct infections are asymptomatic and therefore not treated. Even in
symptomatic cases unless therapy is implemented in a timely and correct manner long-term sequelae including
pelvic inflammatory disease (PID), chronic abdominal pain, ectopic pregnancy and infertility can occur. Thus,
vaccination is the best approach to control chlamydial infections. In this Project we want to test the hypothesis
that a subunit vaccine formulated with Ct antigens elicits robust immune responses and induces cross-serovar
protection in female mice against a genital challenge. To accomplish this goal we are going to test, in C3H/HeN
female mice, vaccines formulated with the Ct major outer membrane protein (MOMP) and the polymorphic
membrane proteins (Ppms). MOMP, MOMP peptides, MOMP DNA and RNA, from Ct senior serovars, will be
formulated and delivered using Nano-Scaffold-Based Nano Lipoprotein Particles (NLP). Immunization with
native MOMP will help guide the production of these vaccine constructs. To enhance protection in the genital
tract, mice will be vaccinated by mucosal and systemic routes using adjuvants. Following vaccination, mucosal
and systemic cellular and humoral immune responses will be determined and correlated with protection.
Vaccinated animals will be challenged transcervically with the eight most clinically relevant Ct serovars.
Protection against infection will be assessed by determining the number of mice with positive vaginal cultures,
the total number of positive vaginal cultures, the length of time mice shed and the severity of vaginal shedding.
To determine protection against long-term sequelae vaccinated and challenged female mice will subsequently
be caged with proven male breeder mice and fertility and upper genital pathology, including hydrosalpinx
formation, will be evaluated. If we cannot obtain a robust, broad cross-serovar protection by vaccinating only
with MOMP, we will test a polyvalent vaccine with MOMP in combination with Ppm C, G or H using NLP. To
ascertain the neutral, additive, synergistic, or antagonistic effects of each antigen, following vaccination,
immune responses to each antigen will be characterized and the data will be correlated with protection. Our
goal is to engineer a safe Nano-Scaffold-Based subunit vaccine that protects mice against a genital challenge
with the Ct serovars that infect the human genital tract. At the end of this project protective vaccine constructs
will be ready for scale-up production and human implementation. An efficacious vaccine against Ct will have a
broad worldwide health and socioeconomic impact.
Terms: <Abdominal Pain><Acute><Adjuvant><Ailmentary System><Alimentary System><Animals><Antibiotic Agents><Antibiotic Drugs><Antibiotics><Antibodies><Antigens><Area><Bio-Informatics><Bioinformatics><Biological><Blindness><Blood Serum><C muridarum><C trachomatis><C. muridarum><C. trachomatis><C3H/HeN Mouse><Cannot achieve a pregnancy><Cell Body><Cells><Chlamydia Infections><Chlamydia muridarum><Chlamydia trachomatis><Chlamydial Infection><Chronic><Classification><Complex><Country><DNA><DNA seq><DNA sequencing><DNAseq><Data><Deoxyribonucleic Acid><Difficulty conceiving><Digestive System><Disease><Disorder><Ectopic Pregnancy><Embryo><Embryonic><Engineering><Eye Infections><Fecundability><Fecundity><Female><Fertility><Gastrointestinal Body System><Gastrointestinal Organ System><Genital><Genital Organs><Genitalia><Goals><Health><Human><Immune memory><Immune response><Immunization><Immunize><Immunologic Memory><Immunologic Sensitization><Immunologic Stimulation><Immunological Memory><Immunological Sensitization><Immunological Stimulation><Immunological response><Immunology><Immunostimulation><In Vitro><Infection><Infertility><Length><Licensure><Lipoproteins><Lymphogranuloma Inguinale><Lymphogranuloma Venereum><MOMP><Mediating><Membrane Protein Gene><Membrane Proteins><Membrane-Associated Proteins><Messenger RNA><Mice><Mice Mammals><Miscellaneous Antibiotic><Modeling><Modern Man><Molecular Configuration><Molecular Conformation><Molecular Stereochemistry><Mucosa><Mucosal Tissue><Mucous Membrane><Murine><Mus><Non-Polyadenylated RNA><Ocular Infections><Partner in relationship><Pathogenesis><Pathology><Pelvic Inflammatory Disease><Peptides><Phylogenetic Analysis><Phylogenetics><Polyvalent Vaccine><Production><Proteins><Pulmonary Body System><Pulmonary Organ System><R-Series Research Projects><R01 Mechanism><R01 Program><RNA><RNA Gene Products><Recombinant Vaccines><Recombinants><Research Grants><Research Project Grants><Research Projects><Respiratory Infections><Respiratory System><Respiratory Tract Infections><Respiratory Tracts><Respiratory tract structure><Ribonucleic Acid><Rickettsia trachomae><Route><Safety><Serology><Serum><Severities><Sexual Transmission><Sexually Transmitted Diseases><Sexually Transmitted Disorder><Sexually Transmitted Infection><Subunit Vaccines><Surface Proteins><Systematics><T-Cells><T-Lymphocyte><Testing><Time><Trachoma><Trees><Vaccinated><Vaccination><Vaccine Production><Vaccines><Vagina><Vaginal><Venereal Diseases><Venereal Disorders><Venereal Infections><Woman><anamnestic reaction><assess effectiveness><bacteria pathogen><bacterial pathogen><base><chlamydia vaccine><chlamydial disease><chronic abdominal pain><clinical relevance><clinically relevant><conformation><conformational state><cytokine><determine effectiveness><develop a vaccine><development of a vaccine><effectiveness assessment><effectiveness evaluation><evaluate effectiveness><extrauterine pregnancy><fertility cessation><fertility loss><gastrointestinal system><genital infection><genital tract><health economics><host response><immune system response><immunogen><immunogenicity><immunoresponse><infertile><mRNA><major outer membrane protein><male><mate><men><men's><nano><nano particle><nano-sized particle><nanolipoprotein particles><nanoparticle><nanosized particle><non-human primate><nonhuman primate><outcome following vaccination><outcome following vaccine><particle><pathogenic bacteria><pelvic inflammatory syndrome><pregnant><produce vaccines><reproductive tract><respiratory><result following vaccination><result following vaccine><scaffold><scaffolding><scale up><secondary immune response><sexually transmitted><socio-economic><socio-economically><socioeconomically><socioeconomics><thymus derived lymphocyte><vaccination outcome><vaccination result><vaccination study><vaccination trial><vaccine development><vaccine effectiveness><vaccine formulation><vaccine outcome><vaccine result><vaccine study><vaccine trial><vision loss><visual loss>