Presentation is loading. Please wait.

Presentation is loading. Please wait.

Anti-Chlamydia Vaccine: From Bench to Bedside

Similar presentations

Presentation on theme: "Anti-Chlamydia Vaccine: From Bench to Bedside"— Presentation transcript:

1 Anti-Chlamydia Vaccine: From Bench to Bedside
Ashlesh Murthy, M.B.B.S., Ph.D Research Assistant Professor University of Texas at San Antonio


3 Chlamydia Obligate intracellular pathogen
C. trachomatis, C. pneumoniae, C. psittaci, C. pecorum, C. muridarum C. trachomatis multiple serovars: A-K, L1-3

4 Chlamydia trachomatis Infections
Trachoma and Inclusion Conjunctivitis Serovars - A, B, Ba, C Urogenital Infections Serovars - D, Da, E, F, G, Ga, H, I, J, K LymphoGranuloma Venereum Serovars - L1, L2, L3

5 Global Prevalence of Chlamydial STD

6 Chlamydial STD Adapted from

7 Chlamydial STD-Ascending Infection
Eskilsden and Gupta et al., In Revision

8 Chlamydial STD-Ascending Infection
PID No Symptoms Dye alone Dye+Chlamydia Vaginitis Cervicitis Endometritis Salpingitis Antimicrobials

9 Chlamydial STD-Reproductive Damage
Pelvic Inflammatory Disease Ectopic pregnancy Infertility Normal

10 Chlamydial STD- Statistics
90 million cases 50-70% of patients initially asymptomatic: not treated 40% of untreated females – pelvic inflammatory disease 20% of PID cases- infertility Adapted from STD statistics

11 Anti-Chlamydial Vaccine

12 Goals for Chlamydial Vaccine
No Symptoms (75%) Immunity Transmission Symptoms (25%) Re-Infection Sequelae Infection Prevent infection (Sterilizing immunity)- ideal Reduce transmission / Duration of shedding- practical Prevent pathological sequelae Protection against multiple serovars

13 Chlamydial Vaccine Trials of 1960s
Formalin-killed whole chlamydial organisms Reduction in incidence for ~ 1 year Comparable/exaggerated ocular pathology in vaccinees Focus on sub-unit vaccines

14 Chlamydial Developmental Cycle

15 Vaccines Against Chlamydial STD
Major outer membrane protein (MOMP) Chlamydia-purified MOMP Recombinant MOMP MOMP DNA MOMP synthetic peptides MOMP plus outer membrane protein 2 (omp2) Chlamydia-purified MOMP refolded to native configuration Cons: MOMP - serovar-specific Currently no licensed vaccine against C. trachomatis Need for identification of new vaccine candidates

16 Chlamydial Developmental Cycle

17 Chlamydial Protease-Like Activity Factor (CPAF)
Secreted into host cytosol Nucleus Inclusion CPAF Overlay

18 CPAF-Human Antibody Responses
Sharma et al., Infect Immun. 2006

19 CPAF-Highly Conserved
Dong et al., Infect Immun. 2005

20 CPAF- A Potential Vaccine Candidate

21 Mouse Model of Chlamydial Infection
C. muridarum 106 Vaginal chlamydial shedding Oviduct dilatation 30 80 Days after challenge

22 Protocol For Vaccination Studies
Intranasal Day –1: IL-12 (0.5 mg) Day 0:rCPAF(15mg)+ IL-12 (0.5 mg) Day +1: IL-12 (0.5 mg) Recombinant CPAF from C. trachomatis L2 cloned into E. coli Day 14: rCPAF (15 mg)+IL-12 (0.5 mg) Day 28: rCPAF (15 mg)+ IL-12 (0.5 mg) 30 day Rest Vaginal challenge Estimation of bacterial shedding Examination of disease pathology Day 60: 5X104 IFU C. muridarum

23 Early Responses to Immunization

24 CPAF Vaccine : Robust IFN-g Response
Murthy et al., Infect Immun. 2007

25 CPAF Vaccine: Systemic Antibodies
Murthy et al., Infect Immun. 2007

26 CPAF Vaccine: Mucosal Antibodies
Murthy et al., Infect Immun. 2007

27 CPAF Vaccine: Chlamydial Clearance
Murthy et al., Infect Immun. 2007

28 CPAF+IL-12: Prevents Hydrosalpinx
Murthy et al., Infect Immun. 2007

29 CPAF Vaccine: Preserves Fertility
Murthy et al., In Review, 2010

30 Role of Human HLA-DR Murthy et al., Infect Immun. 2006

31 Minimal Role for Antibody
Murthy et al., FEMS Immunol. Med. Microbiol. 2009

32 Role of CD4+ T-cells CD4+ T cell adoptive transfer
Murphey et al., Cell. Immunol. 2006

33 Role of IFN-g Murthy et al., J. Immunol. 2008

34 Summary CPAF vaccine administered with Th1 adjuvant:
Enhances clearance of infection Protects against severe pathology Induces robust cellular IFN-g response Induces systemic and mucosal antibody Protection is dependent upon CPAF-specific cellular IFN-g responses but not antibody

35 Ongoing Collaborative Effort
US Patent Application No. 12/243,769: Inventors- Arulanandam, Murthy, Zhong

36 Bench to Bedside Anti-Chlamydia vaccine
Identification of pathogenic mechanisms Vaccine antigen discovery Validation of protection and pathogenesis correlates in clinical samples Routes, Delivery systems Adjuvants, Formulations Non-Human Primates Clinical Trials Anti-Chlamydia vaccine

37 Acknowledgements Bernard Arulanandam, Ph.D., M.B.A.
Weidang Li, M.D., Ph.D. Bharat Chaganty, MS Sangamithra Kamalakaran, B.Tech Kishan Evani, MS Rishein Gupta, Ph.D. Yu Cong, M.D. Madhulika Jupelli, Ph.D. Cathi Murphey, M.S. Guangming Zhong, M.D., Ph.D., UTHSCSA M. Neal Guentzel, Ph.D., STCEID, UTSA Aruna Mittal, Ph.D, IOP, India 1R03AI088342


Download ppt "Anti-Chlamydia Vaccine: From Bench to Bedside"

Similar presentations

Ads by Google