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Ashlesh Murthy, M.B.B.S., Ph.D Research Assistant Professor University of Texas at San Antonio 1.

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Presentation on theme: "Ashlesh Murthy, M.B.B.S., Ph.D Research Assistant Professor University of Texas at San Antonio 1."— Presentation transcript:

1 Ashlesh Murthy, M.B.B.S., Ph.D Research Assistant Professor University of Texas at San Antonio 1

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3 Obligate intracellular pathogen C. trachomatis, C. pneumoniae, C. psittaci, C. pecorum, C. muridarum C. trachomatis multiple serovars: A-K, L 1-3 3

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

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6 Adapted from 6

7 Eskilsden and Gupta et al., In Revision 7

8 Vaginitis Cervicitis Endometritis Salpingitis PID No Symptoms Antimicrobials Dye aloneDye+Chlamydia 8

9 Normal Pelvic Inflammatory Disease Ectopic pregnancy Infertility 9

10 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 statisticswww.cdc.gov- 10

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

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

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15 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 15

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

18 Sharma et al., Infect Immun CPAF 18

19 Dong et al., Infect Immun

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21 Days after challenge Vaginal chlamydial shedding Oviduct dilatation 10 6 C. muridarum 21

22 Day –1: IL-12 (0.5 g) Day 0:rCPAF(15 g)+ IL-12 (0.5 g) Day +1: IL-12 (0.5 g) Day 28: rCPAF (15 g)+ IL-12 (0.5 g) Day 14: rCPAF (15 g)+IL-12 (0.5 g) Day 60: 5X10 4 IFU C. muridarum Estimation of bacterial shedding Examination of disease pathology Intranasal Vaginal challenge Protocol For Vaccination Studies Recombinant CPAF from C. trachomatis L2 cloned into E. coli 30 day Rest 22

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24 Murthy et al., Infect Immun

25 Murthy et al., Infect Immun

26 Murthy et al., Infect Immun

27 Murthy et al., Infect Immun

28 Murthy et al., Infect Immun

29 Murthy et al., In Review,

30 Murthy et al., Infect Immun

31 Murthy et al., FEMS Immunol. Med. Microbiol

32 CD4 + T cell adoptive transfer Murphey et al., Cell. Immunol

33 Murthy et al., J. Immunol

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

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

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

37 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 1R03AI

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