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1. 419 Intramuscular immunization with rVCG-MECA vaccine elicits stronger chlamydial specific immune response than intranasal immunization

Author

Medhavi FNU, Tanner Tayhlor, Richardson Shakyra, Jones Leandra, Bell Counrtnee, Josesph U. Igietseme, Omosun Yusuf, and Eko Francis

Subjects
Medicine
Abstract

OBJECTIVES/GOALS: We prioritize Chlamydia’s public health impact, aim to develop rVCG-MECA for practical use, study robust immunity for effective strategies, and assess animal models for human vaccination adaptation. Our work highlights rVCG-MECA’s translational significance in public health. METHODS/STUDY POPULATION: Female Mice C57BL/6J mice (N=8) were immunized intramuscularly(IM) and intranasally(IN) and boosted twice, two weeks apart, with rVCG-MECA, once with live Chlamydia (C. trachomatis serovar D elementary bodies) and PBS. Specific mucosal and systemic immune responses were characterized. Vaccine efficacy was determined from chlamydia shedding following the transcervical challenge. Additionally, Chlamydia-specific cytokine (IFN-γ and IL-4) production by splenic and ILN T cells was assessed after 16 weeks RESULTS/ANTICIPATED RESULTS: Immunization with rVCG-MECA via intramuscular and intranasal routes triggered notable humoral responses in systemic and mucosal tissues. Intramuscular vaccination produced higher IgG2c levels in both tissues, while intranasal vaccination led to elevated IgA levels in mucosal tissues. rVCG-MECA-immunized mice exhibited significantly higher IFN-γ (Th1) secretion compared to IL-4 (Th2), with intramuscular immunization showing the highest IFN-γ levels. These findings anticipate robust immune responses, promising protection against Chlamydia, particularly through the intra muscular route. Overall, our results support rVCG-MECA as a promising Chlamydia vaccine, aligned with public health goals. DISCUSSION/SIGNIFICANCE: This study suggests that IM and IN immunization with rVCG-MECA induces immune effectors such as IFN-gamma and IgG2c that mediate chlamydial clearance in the genetical tract.

Published
2024
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7. A novel cold-chain free VCGbased subunit vaccine protects against Chlamydia abortus-induced neonatal mortality in a pregnant mouse model.

Author

Richardson, Shakyra, Bell, Courtnee R., Medhavi, Fnu, Tanner, Tayhlor, Lundy, Stephanie, Omosun, Yusuf, Igietseme, Joseph U., and Eko, Francis O.

Subjects
NEONATAL mortality, LABORATORY mice, CHLAMYDIA, GENITALIA, ANIMAL disease models
Abstract

Chlamydia abortus (Cab) causes spontaneous abortion and neonatal mortality in infected ruminants and pregnant women. Most Cab infections are asymptomatic, although they can be treated with antibiotics, signifying that control of these infections may require alternative strategies, including the use of effective vaccines. However, the limitations imposed by live attenuated and inactivated vaccines further suggest that employment of subunit vaccines may need to be considered. The efficacy of a newly generated Vibrio cholerae ghost (rVCG)-based subunit vaccine harboring the N-terminal portion of the Cab Pmp18D protein (rVCG-Pmp18.3) in preventing Cab-induced abortion or neonatal mortality was evaluated in pregnant mice. Mice were intranasally (IN) immunized and boosted twice, 2 weeks apart with the vaccine, and immunized and unimmunized mice were caged with males 4 weeks postimmunization. The mice were then infected either IN or transcervically (TC) 10 days after pregnancy, and the fertility rate was determined 7 days postpartum. Eight days after delivery, the mice were sacrificed, and Cab infectivity in the lungs and spleens was evaluated by culturing tissue homogenates in tissue culture. Our results demonstrated that the vaccine induced immune effectors that mediated complete clearance of infection in the lungs and significantly reduced Cab infectivity in the spleen following IN immunization. Vaccine immunization also afforded protection against Cab-induced upper genital tract pathology (uterine dilation). Furthermore, while there was no incidence of abortion in both immunized and unimmunized mice, immunized mice were completely protected against neonatal mortality compared to unimmunized infected controls, which lost a significant percentage of their litter 7 days postpartum. Our results establish the capability of the rVCG-Pmp18.3 vaccine to prevent infection in the lungs (mucosal) and spleen (systemic) and protect mice from Cab-induced tubal pathologies and neonatal mortality, a hallmark of Cab infection in ruminants. To advance the commercial potential of this vaccine, future studies will optimize the antigen dose and the number of vaccine doses required for protection of ruminants. [ABSTRACT FROM AUTHOR]

Published
2023
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11. Genital tract microbiome dynamics are associated with time of Chlamydia infection in mice.

Author

Zhao, Lihong, Lundy, Stephanie R., Eko, Francis O., Igietseme, Joeseph U., and Omosun, Yusuf O.

Subjects
GENITALIA, CHLAMYDIA infections, GENITALIA infections, MICE, OVIDUCT
Abstract

We have previously shown that the time of Chlamydia infection was crucial in determining the chlamydial infectivity and pathogenesis. This study aims to determine whether the time of Chlamydia infection affects the genital tract microbiome. This study analyzed mice vaginal, uterine, and ovary/oviduct microbiome with and without Chlamydia infection. The mice were infected with Chlamydia at either 10:00 am (ZT3) or 10:00 pm (ZT15). The results showed that mice infected at ZT3 had higher Chlamydia infectivity than those infected at ZT15. There was more variation in the compositional complexity of the vaginal microbiome (alpha diversity) of mice infected at ZT3 than those mice infected at ZT15 throughout the infection within each treatment group, with both Shannon and Simpson diversity index values decreased over time. The analysis of samples collected four weeks post-infection showed that there were significant taxonomical differences (beta diversity) between different parts of the genital tract—vagina, uterus, and ovary/oviduct—and this difference was associated with the time of infection. Firmicutes and Proteobacteria were the most abundant phyla within the microbiome in all three genital tract regions for all the samples collected during this experiment. Additionally, Firmicutes was the dominant phylum in the uterine microbiome of ZT3 Chlamydia infected mice. The results show that the time of infection is associated with the microbial dynamics in the genital tract. And this association is more robust in the upper genital tract than in the vagina. This result implies that more emphasis should be placed on understanding the changes in the microbial dynamics of the upper genital tract over the course of infection. [ABSTRACT FROM AUTHOR]

Published
2023
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40. The molecular mechanism of induction of unfolded protein response by Chlamydia

Author

George, Zenas, primary, Omosun, Yusuf, additional, Azenabor, Anthony A., additional, Goldstein, Jason, additional, Partin, James, additional, Joseph, Kahaliah, additional, Ellerson, Debra, additional, He, Qing, additional, Eko, Francis, additional, McDonald, Melissa A., additional, Reed, Matthew, additional, Svoboda, Pavel, additional, Stuchlik, Olga, additional, Pohl, Jan, additional, Lutter, Erika, additional, Bandea, Claudiu, additional, Black, Carolyn M., additional, and Igietseme, Joseph U., additional

Published
2019
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42. Molecular Pathogenesis of Chlamydia Disease Complications: Epithelial-Mesenchymal Transition and Fibrosis

Author

Igietseme, Joseph U., primary, Omosun, Yusuf, additional, Nagy, Tamas, additional, Stuchlik, Olga, additional, Reed, Matthew S., additional, He, Qing, additional, Partin, James, additional, Joseph, Kahaliah, additional, Ellerson, Debra, additional, George, Zenas, additional, Goldstein, Jason, additional, Eko, Francis O., additional, Bandea, Claudiu, additional, Pohl, Jan, additional, and Black, Carolyn M., additional

Published
2018
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47. The roles of unfolded protein response pathways in Chlamydia pathogenesis

Author

George, Zenas, primary, Omosun, Yusuf, additional, Azenabor, Anthony A., additional, Partin, James, additional, Joseph, Kahaliah, additional, Ellerson, Debra, additional, He, Qing, additional, Eko, Francis, additional, Bandea, Claudiu, additional, Svoboda, Pavel, additional, Pohl, Jan, additional, Black, Carolyn M., additional, and Igietseme, Joseph U., additional

Published
2016
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