Increased immunoaccessibility of MOMP epitopes in a vaccine formulated with amphipols may account for the very robust protection elicited against a vaginal challenge with Chlamydia muridarum.
There is a need to implement a vaccine to protect against Chlamydia trachomatis infections. To test a new vaccine, mice were immunized with the Chlamydia muridarum native major outer membrane protein (nMOMP) solubilized with either amphipol A8-35 or the detergent Z3-14. OVA was used as a negative control, and mice were inoculated intranasally with C. muridarum as positive controls. Animals vaccinated with nMOMP mounted strong Chlamydia-specific humoral and cell-mediated immune responses. Mice vaccinated with nMOMP/A8-35 had a higher ratio of Abs to denatured elementary bodies (EB) over live EB, recognized more synthetic MOMP peptides and had higher neutralizing titers than sera from mice immunized with nMOMP/Z3-14. T cell lymphoproliferative responses and levels of IFN-γ were also higher in mice vaccinated with nMOMP/A8-35 than with nMOMP/Z3-14. Following immunization, animals were challenged intravaginally with C. muridarum. On the basis of the number of mice with positive vaginal cultures, length of vaginal shedding, total number of positive vaginal cultures, and number of Chlamydia inclusion forming units recovered, nMOMP/A8-35 elicited a more robust protection than nMOMP/Z3-14. By depleting T cells with Abs, we determined that CD4(+) and not CD8(+) T cells mediated the protection elicited by nMOMP/A8-35. Mice were subsequently mated, and based on the number of pregnant mice and number of embryos, animals that were vaccinated with nMOMP/A8-35 or nMOMP/Z3-14 had fertility rates equivalent to the positive control group immunized with live EB and the fertility controls. In conclusion, increased accessibility of epitopes in the nMOMP/A8-35 preparation may account for the very robust protection against infection and disease elicited by this vaccine.
Department of Pathology and Laboratory Medicine, Medical Sciences I, University of California, Irvine, Irvine, CA 92697;
Delia F
DF
Tifrea
Department of Pathology and Laboratory Medicine, Medical Sciences I, University of California, Irvine, Irvine, CA 92697;
Sukumar
S
Pal
Centre National de la Recherche Scientifique/Université Paris-7 Unité Mixte de Recherche 7099, Institut de Biologie Physico-Chimique, F-75005 Paris, France; and.
Jean-Luc
JL
Popot
Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA 92697.
Melanie J
MJ
Cocco
Department of Pathology and Laboratory Medicine, Medical Sciences I, University of California, Irvine, Irvine, CA 92697; lmdelama@uci.edu.
Luis M
LM
de la Maza
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology* / Q000494:pharmacology; D001428:Bacterial Vaccines / Q000276:immunology* / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002690:Chlamydia Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D023502:Chlamydia muridarum / Q000276:immunology*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D011437:Propylamines / Q000276:immunology / Q000494:pharmacology
D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D011437:Propylamines