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

Abstract

There is a need to implement a vaccine to protect against Chlamydia trachomatis infections. To test a new vaccine mice were immunized with the C. muridarum native major outer membrane protein (nMOMP) solubilized with either amphipol A8-35 or the detergent Z3-14. Ovalbumin was used as a negative control and mice 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 antibodies to denatured 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. Based on 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 antibodies 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 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.

The Chlamydia M278 Major Outer Membrane Peptide Encapsulated in the Poly(lactic acid)-Poly(ethylene glycol) Nanoparticulate Self-Adjuvanting Delivery System Protects Mice Against a Chlamydia muridarum Genital Tract Challenge by Stimulating Robust Systemic and Local Mucosal Immune Responses

“…Additionally, immunofluorescence microscopy images provide direct confirmation of the lesser number of inclusions in cells exposed to swabs collected from PPM as compared to those from PPP and M278 immunized mice (Figure 1B ). By day 21 post-challenge the infection was cleared spontaneously in all mice; a finding that has been reported by other investigators ( 21 , 48 , 49 ). These encouraging results provide the first evidence that the PPM nanovaccine is efficacious in providing protection against a homologous chlamydial genital challenge in mice.…”

The Chlamydia M278 Major Outer Membrane Peptide Encapsulated in the Poly(lactic acid)-Poly(ethylene glycol) Nanoparticulate Self-Adjuvanting Delivery System Protects Mice Against a Chlamydia muridarum Genital Tract Challenge by Stimulating Robust Systemic and Local Mucosal Immune Responses

“…Additionally, immunofluorescence microscopy images provide direct confirmation of the lesser number of inclusions in cells exposed to swabs collected from PPM as compared to those from PPP and M278 immunized mice (Figure 1B ). By day 21 post-challenge the infection was cleared spontaneously in all mice; a finding that has been reported by other investigators ( 21 , 48 , 49 ). These encouraging results provide the first evidence that the PPM nanovaccine is efficacious in providing protection against a homologous chlamydial genital challenge in mice.…”

Chlamydial protease‐like activity factor mediated protection against C. trachomatis in guinea pigs

“…C. trachomatis (CT-D) immunization exhibited rapid bacterial clearance and significant reduction in upper genital pathology following a secondary intravaginal chlamydial challenge. These results are consistent with those from the mouse model 41 , 43 and guinea pig vaccination studies 25 , 31 wherein, robust protection against genital chlamydial challenge is induced by live chlamydial EB immunization. Hydrosalpinx (fluid-filled oviduct dilatations) are a characteristic feature of pathological sequelae following chlamydial infections in their respective hosts.…”

A vaccine formulated with the major outer membrane protein can protect C3H/HeN, a highly susceptible strain of mice, from a Chlamydia muridarum genital challenge

“…These findings, in conjunction with previous results in BALB/c and C57BL/6 mice, provide support for the feasibility of engineering a subunit vaccine against C. trachomatis infections that can be effective in populations with different genetic backgrounds . Although others have reported protection against a vaginal challenge, to the best of our knowledge, only a subunit vaccine formulated with MOMP, and adjuvants that favour a Th1 response, have been shown to protect three strains of mice, with different genetic backgrounds, against an upper genital challenge with Chlamydia …”

The Chlamydia M278 Major Outer Membrane Peptide Encapsulated in the Poly(lactic acid)-Poly(ethylene glycol) Nanoparticulate Self-Adjuvanting Delivery System Protects Mice Against a Chlamydia muridarum Genital Tract Challenge by Stimulating Robust Systemic and Local Mucosal Immune Responses

“…Additionally, immunofluorescence microscopy images provide direct confirmation of the lesser number of inclusions in cells exposed to swabs collected from PPM as compared to those from PPP and M278 immunized mice (Figure 1B ). By day 21 post-challenge the infection was cleared spontaneously in all mice; a finding that has been reported by other investigators ( 21 , 48 , 49 ). These encouraging results provide the first evidence that the PPM nanovaccine is efficacious in providing protection against a homologous chlamydial genital challenge in mice.…”

Chlamydial protease‐like activity factor mediated protection against C. trachomatis in guinea pigs

“…C. trachomatis (CT-D) immunization exhibited rapid bacterial clearance and significant reduction in upper genital pathology following a secondary intravaginal chlamydial challenge. These results are consistent with those from the mouse model 41 , 43 and guinea pig vaccination studies 25 , 31 wherein, robust protection against genital chlamydial challenge is induced by live chlamydial EB immunization. Hydrosalpinx (fluid-filled oviduct dilatations) are a characteristic feature of pathological sequelae following chlamydial infections in their respective hosts.…”

A vaccine formulated with the major outer membrane protein can protect C3H/HeN, a highly susceptible strain of mice, from a Chlamydia muridarum genital challenge

“…These findings, in conjunction with previous results in BALB/c and C57BL/6 mice, provide support for the feasibility of engineering a subunit vaccine against C. trachomatis infections that can be effective in populations with different genetic backgrounds . Although others have reported protection against a vaginal challenge, to the best of our knowledge, only a subunit vaccine formulated with MOMP, and adjuvants that favour a Th1 response, have been shown to protect three strains of mice, with different genetic backgrounds, against an upper genital challenge with Chlamydia …”

The Chlamydia M278 Major Outer Membrane Peptide Encapsulated in the Poly(lactic acid)-Poly(ethylene glycol) Nanoparticulate Self-Adjuvanting Delivery System Protects Mice Against a Chlamydia muridarum Genital Tract Challenge by Stimulating Robust Systemic and Local Mucosal Immune Responses

“…Additionally, immunofluorescence microscopy images provide direct confirmation of the lesser number of inclusions in cells exposed to swabs collected from PPM as compared to those from PPP and M278 immunized mice (Figure 1B ). By day 21 post-challenge the infection was cleared spontaneously in all mice; a finding that has been reported by other investigators ( 21 , 48 , 49 ). These encouraging results provide the first evidence that the PPM nanovaccine is efficacious in providing protection against a homologous chlamydial genital challenge in mice.…”

Chlamydial protease‐like activity factor mediated protection against C. trachomatis in guinea pigs

“…C. trachomatis (CT-D) immunization exhibited rapid bacterial clearance and significant reduction in upper genital pathology following a secondary intravaginal chlamydial challenge. These results are consistent with those from the mouse model 41 , 43 and guinea pig vaccination studies 25 , 31 wherein, robust protection against genital chlamydial challenge is induced by live chlamydial EB immunization. Hydrosalpinx (fluid-filled oviduct dilatations) are a characteristic feature of pathological sequelae following chlamydial infections in their respective hosts.…”

A vaccine formulated with the major outer membrane protein can protect C3H/HeN, a highly susceptible strain of mice, from a Chlamydia muridarum genital challenge

“…These findings, in conjunction with previous results in BALB/c and C57BL/6 mice, provide support for the feasibility of engineering a subunit vaccine against C. trachomatis infections that can be effective in populations with different genetic backgrounds . Although others have reported protection against a vaginal challenge, to the best of our knowledge, only a subunit vaccine formulated with MOMP, and adjuvants that favour a Th1 response, have been shown to protect three strains of mice, with different genetic backgrounds, against an upper genital challenge with Chlamydia …”