title: Induction of protection against vaginal shedding and infertility by a recombinant Chlamydia vaccine.
abstract: A vaccine formulated with the Chlamydia muridarum recombinant major outer membrane protein, plus the adjuvants CpG and Montanide, was tested for its ability to protect BALB/c mice against a vaginal challenge. Mice were immunized by mucosal [intravaginal (i.vag.) plus colonic (col.), or intranasal (i.n.) plus sublingual (s.l.)], or systemic [intramuscular (i.m.) plus subcutaneous (s.c.)] routes, and a combination of mucosal priming and systemic boosting routes. A negative control group was vaccinated with the Neisseria gonorrhoeae porin B (Ng-rPorB) and a positive control group was inoculated in the nares with live Chlamydia. The strongest Chlamydia-specific humoral and cell-mediated immune responses were observed in the groups immunized by a combination of mucosal and systemic routes. Following the vaginal challenge, groups immunized using mucosal priming followed by systemic immunization had a significant decrease in the number of mice with positive vaginal cultures. For example, of the mice immunized i.n./s.l.+i.m./s.c., 24% had positive cultures during the six weeks of the experiment versus 69% for the negative control group immunized with Ng-rPorB (P<0.05). Similarly, the groups of mice primed by the mucosal routes and boosted by the systemic routes had significantly less IFU in the vaginal cultures when compared to the Ng-rPorB animals (P<0.05). These combination groups were also protected against infertility. The two groups had fertility rates of 100% (i.n./s.l.+i.m./s.c.) and 81% (i.vag./col.+i.m./s.c.) equivalent to the positive-control group immunized with live Chlamydia (100% fertility; P>0.05). These results show the importance of the schedule and routes of vaccination and represent the first study to show protection against infertility by a Chlamydia recombinant subunit vaccine.
authors: Department of Pathology and Laboratory Medicine, Medical Sciences, Room D440, University of California, Irvine, Irvine, CA 92697-4800, USA.
authors: Jennifer R
authors: JR
authors: Carmichael
authors: Sukumar
authors: S
authors: Pal
authors: Delia
authors: D
authors: Tifrea
authors: Luis M
authors: LM
authors: de la Maza
references: Sex Transm Dis. 1992 Jul-Aug;19(4):185-92
references: 1411832
references: Vaccine. 1991 Feb;9(2):129-33
references: 2058260
references: Nat Med. 2005 Apr;11(4 Suppl):S45-53
references: 15812489
references: Infect Immun. 1995 Dec;63(12):4661-8
references: 7591120
references: Infect Immun. 2000 Jul;68(7):4207-16
references: 10858238
references: Vaccine. 2008 May 23;26(22):2796-806
references: 18440102
references: J Virol. 2003 Apr;77(8):4558-65
references: 12663762
references: Oral Microbiol Immunol. 1998 Jun;13(3):139-49
references: 10093528
references: J Infect Dis. 2004 Nov 1;190(9):1697-705
references: 15478078
references: Vaccine. 2009 Aug 6;27(36):5020-5
references: 19446590
references: Curr HIV Res. 2004 Jan;2(1):1-10
references: 15053336
references: Clin Immunol. 2007 May;123(2):166-75
references: 17349825
references: Proc Natl Acad Sci U S A. 1988 Jun;85(11):4000-4
references: 2453883
references: Infect Immun. 1981 Mar;31(3):1161-76
references: 7228399
references: Gene. 1991 Sep 30;106(1):137-8
references: 1937036
references: Infect Immun. 1994 May;62(5):2094-7
references: 8168974
references: Biochem J. 1986 Nov 15;240(1):1-12
references: 3548705
references: J Immunol. 2009 Jun 15;182(12):8063-70
references: 19494332
references: Sex Transm Dis. 1978 Apr-Jun;5(2):73-7
references: 10328037
references: J Infect Dis. 2010 Jun 15;201 Suppl 2:S96-103
references: 20470047
references: Infect Immun. 2002 Jun;70(6):2741-51
references: 12010958
references: Immunology. 2003 Sep;110(1):86-94
references: 12941145
references: J Virol. 2003 Sep;77(18):9845-51
references: 12941893
references: J Immunol. 2000 Nov 1;165(9):4778-82
references: 11045998
references: Sex Transm Dis. 2005 Jan;32(1):49-56
references: 15614121
references: Scand J Immunol. 1996 Oct;44(4):408-14
references: 8845036
references: Science. 1942 Jan 9;95(2454):49-50
references: 17773453
references: Vaccine. 2007 Dec 21;26(1):67-76
references: 18061315
references: Vaccine. 2007 Dec 12;25(51):8598-610
references: 17996991
references: Infect Immun. 2005 Dec;73(12):8153-60
references: 16299310
references: Vaccine. 1998 Aug;16(13):1257-62
references: 9682388
references: J Infect Dis. 1975 Jul;132(1):87-105
references: 1097546
references: N Engl J Med. 2004 Feb 26;350(9):896-903
references: 14985487
references: J Immunol. 1999 Apr 15;162(8):5011-8
references: 10202050
references: Infect Immun. 1988 Apr;56(4):885-91
references: 3346076
references: JAMA. 2004 May 12;291(18):2229-36
references: 15138245
references: J Immunol. 1996 Nov 15;157(10):4554-67
references: 8906834
references: Vaccine. 2007 Jul 26;25(30):5467-84
references: 17227687
references: Infect Immun. 1994 Aug;62(8):3354-62
references: 8039906
references: J Reprod Immunol. 1988 Nov;14(2):165-76
references: 3070026
references: Am J Ophthalmol. 1967 May;63(5):Suppl:1615-30
references: 4960884
references: Vaccine. 2010 Feb 17;28(7):1668-72
references: 20026449
references: Vaccine. 2008 Jan 30;26(5):639-46
references: 18178292
references: MMWR Morb Mortal Wkly Rep. 2009 Apr 17;58(14):362-5
references: 19373196
references: Eur J Immunol. 2002 Aug;32(8):2274-81
references: 12209640
references: Curr Opin Investig Drugs. 2002 Jul;3(7):980-6
references: 12186275
references: Infect Immun. 1994 Jun;62(6):2432-9
references: 8188368
references: Infect Immun. 2002 Sep;70(9):4812-7
references: 12183524
references: J Infect Dis. 2008 Sep 1;198(5):758-67
references: 18652549
references: Infect Immun. 2010 Mar;78(3):1202-13
references: 20048043
references: Vaccine. 1995 Jan;13(1):119-27
references: 7762268