Immunization with the Chlamydia trachomatis mouse pneumonitis major outer membrane protein by use of CpG oligodeoxynucleotides as an adjuvant induces a protective immune response against an intranasal chlamydial challenge.
Recently, we have shown that a vaccine consisting of a purified preparation of the Chlamydia trachomatis mouse pneumonitis (MoPn) major outer membrane protein (MOMP) and Freund's adjuvant can protect mice against a genital challenge. Here, we wanted to determine if CpG motifs could be used as an immune modulator to the MOMP to induce protection in mice against an intranasal (i.n.) challenge. One-week-old BALB/c mice were immunized intramuscularly and subcutaneously either once or three times at 2-week intervals with MOMP and CpG suspended in aluminum hydroxide (alum). Negative controls received ovalbumin, CpG, and alum. Positive controls were immunized i.n. with C. trachomatis MoPn elementary bodies (EB). Six weeks after the last immunization, mice were challenged i.n. with 10(4) inclusion-forming units (IFU) of the C. trachomatis MoPn serovar. Mice that received MOMP, CpG, and alum had a strong immune response, as shown by a high titer of serum antibodies to Chlamydia and significant lymphoproliferation of T-cells following stimulation with C. trachomatis EB. After the i.n. challenge mice immunized with MOMP, CpG, and alum showed significantly less body weight loss than the corresponding control mice immunized with ovalbumin, CpG, and alum. Ten days after the challenge the animals were euthanized, their lungs were weighed, and the numbers of IFU in the lungs were determined. The average weight of the lungs of the mice immunized with MOMP, CpG, and alum was significantly less than average weight of the lungs of the mice immunized with ovalbumin, CpG, and alum. Also, the average number of IFU recovered per mouse immunized with MOMP, CpG, and alum was significantly less than the average number of IFU per mouse detected in the mice inoculated with ovalbumin, CpG, and alum. In conclusion, our data show that CpG sequences can be used as an effective adjuvant with the C. trachomatis MoPn MOMP to elicit a protective immune response in mice against a chlamydial respiratory challenge.
Department of Pathology, Medical Sciences, University of California, Irvine, Irvine, California 92697-4800, USA.
Sukumar
S
Pal
Heather L
HL
Davis
Ellena M
EM
Peterson
Luis M
LM
de la Maza
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage; D001835:Body Weight; D002690:Chlamydia Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D002692:Chlamydia trachomatis / Q000276:immunology* / Q000472:pathogenicity*; D018899:CpG Islands; D005260:Female; D007114:Immunization; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000276:immunology*; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D018272:Porins / Q000008:administration & dosage* / Q000276:immunology*
D000276:Adjuvants, Immunologic; D001428:Bacterial Vaccines; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D018272:Porins; C071677:omp1 protein, Chlamydia trachomatis