scholarly journals Induction of protection in mice against a respiratory challenge by a vaccine formulated with exosomes isolated from Chlamydia muridarum infected cells

npj Vaccines ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Sukumar Pal ◽  
Yeva Mirzakhanyan ◽  
Paul Gershon ◽  
Delia F. Tifrea ◽  
Luis M. de la Maza
Keyword(s):  
Mass Spectrometry ◽  
Body Weight ◽  
Membrane Protein ◽  
Immune Responses ◽  
Hela Cells ◽  
Outer Membrane Protein ◽  
Chlamydia Muridarum ◽  
Infected Cells ◽  
Respiratory Challenge ◽  
Negative Controls

Abstract The goal of this study was to determine if exosomes, isolated from Chlamydia muridarum infected HeLa cells (C. muridarum-exosomes), induce protective immune responses in mice following vaccination using CpG plus Montanide as adjuvants. Exosomes, collected from uninfected HeLa cells and PBS, formulated with the same adjuvants, were used as negative controls. Mass spectrometry analyses identified 113 C. muridarum proteins in the C. muridarum-exosome preparation including the major outer membrane protein and the polymorphic membrane proteins. Vaccination with C. muridarum-exosomes elicited robust humoral and cell-mediated immune responses to C. muridarum elementary bodies. Following vaccination, mice were challenged intranasally with C. muridarum. Compared to the negative controls, mice immunized with C. muridarum-exosomes were significantly protected as measured by changes in body weight, lungs’ weight, and number of inclusion forming units recovered from lungs. This is the first report, of a vaccine formulated with Chlamydia exosomes, shown to elicit protection against a challenge.

scholarly journals Induction of Protection in Mice against a Chlamydia muridarum Respiratory Challenge by a Vaccine Formulated with the Major Outer Membrane Protein in Nanolipoprotein Particles

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 755
Author(s):  
Delia F. Tifrea ◽  
Wei He ◽  
Sukumar Pal ◽  
Angela C. Evans ◽  
Sean F. Gilmore ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Major Outer Membrane Protein ◽  
Free System ◽  
Chlamydia Muridarum ◽  
Sexually Transmitted ◽  
A Cell ◽  
Respiratory Challenge ◽  
First Time

Chlamydia trachomatis is a sexually transmitted bacterium that infects over 130 million individuals worldwide annually. To implement a vaccine, we developed a cell-free co-translational system to express the Chlamydia muridarum major outer membrane protein (MOMP). This approach uses a nanolipoprotein particles (tNLP) made from ApoA1 protein, amphiphilic telodendrimer and lipids that self-assemble to form 10–25 nm discs. These tNLP provide a protein-encapsulated lipid support to solubilize and fold membrane proteins. The cell-free system co-translated MOMP and ApoA1 in the presence of telodendrimer mixed with lipids. The MOMP-tNLP complex was amenable to CpG and FSL-1 adjuvant addition. To investigate the ability of MOMP-tNLP+CpG+FSL-1 to induce protection against an intranasal (i.n.) C. muridarum challenge, female mice were vaccinated intramuscularly (i.m.) or i.n. and i.m. simultaneously 4 weeks apart. Following vaccination with MOMP-tNLP+CpG+FSL-1, mice mounted significant humoral and cell-mediated immune responses. Following the i.n. challenge, mice vaccinated with MOMP-tNLP+CpG+FSL-1 i.n. + i.m. group were protected as determined by the percentage change in body weight and by the number of C. muridarum inclusion forming units (IFU) recovered from the lungs. To our knowledge, this is the first time a MOMP-based vaccine formulated in tNLP has been shown to protect against C. muridarum.

scholarly journals A Recombinant Chlamydia trachomatis MOMP Vaccine Elicits Cross-serogroup Protection in Mice Against Vaginal Shedding and Infertility

2019 ◽  
Vol 221 (2) ◽  
pp. 191-200 ◽  
Author(s):  
Delia F Tifrea ◽  
Sukumar Pal ◽  
Luis M de la Maza
Keyword(s):  
Chlamydia Trachomatis ◽  
Membrane Protein ◽  
Immune Responses ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Subunit Vaccine ◽  
Bacterial Pathogen ◽  
Male Mice ◽  
Fertility Rates ◽  
Sexually Transmitted

Abstract Background Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen worldwide. Here, we determined the ability of a C. trachomatis recombinant major outer membrane protein (rMOMP) vaccine to elicit cross-serogroup protection. Methods Female C3H/HeN mice were vaccinated by mucosal and systemic routes with C. trachomatis serovar D (UW-3/Cx) rMOMP and challenged in the ovarian bursa with serovars D (UW-3/Cx), D (UCI-96/Cx), E (IOL-43), or F (N.I.1). CpG-1826 and Montanide ISA 720 were used as adjuvants. Results Immune responses following vaccination were more robust against the most closely related serovars. Following a genital challenge (as determined by number of mice with positive vaginal cultures, number of positive cultures, number of inclusion forming units recovered, and number of days with positive cultures) mice challenged with C. trachomatis serovars of the same complex were protected but not those challenged with serovar F (N.I.1) from a different subcomplex. Females were caged with male mice. Based on fertility rates, number of embryos, and hydrosalpinx formation, vaccinated mice were protected against challenges with serovars D (UW-3/Cx), D (UCI-96/Cx), and E (IOL-43) but not F (N.I.1). Conclusions This is the first subunit vaccine shown to protect mice against infection, pathology, and infertility caused by different C. trachomatis serovars.

The effect of Chlamydophila pneumoniae Major Outer Membrane Protein (MOMP) on macrophage and T cell-mediated immune responses

Immunobiology ◽  
2011 ◽  
Vol 216 (1-2) ◽  
pp. 152-163 ◽  
Author(s):  
Alexandra Bermudez-Fajardo ◽  
Anne-Katrien Stark ◽  
Rehab El-Kadri ◽  
Manuel L. Penichet ◽  
Katharina Hölzle ◽  
...  
Keyword(s):  
T Cell ◽  
Membrane Protein ◽  
Immune Responses ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Chlamydophila Pneumoniae ◽  
Major Outer Membrane Protein

scholarly journals Priming with Chlamydia trachomatis Major Outer Membrane Protein (MOMP) DNA followed by MOMP ISCOM Boosting Enhances Protection and Is Associated with Increased Immunoglobulin A and Th1 Cellular Immune Responses

2000 ◽  
Vol 68 (6) ◽  
pp. 3074-3078 ◽  
Author(s):  
Zhang Dong-Ji ◽  
Xi Yang ◽  
Caixia Shen ◽  
Hong Lu ◽  
Andrew Murdin ◽  
...  
Keyword(s):  
Chlamydia Trachomatis ◽  
Membrane Protein ◽  
Immune Responses ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Immunoglobulin A ◽  
Major Outer Membrane Protein ◽  
Delayed Type Hypersensitivity ◽  
Cellular Immune Responses ◽  
Cellular Immune

ABSTRACT We previously reported that DNA vaccination was able to elicit cellular immune responses and partial protection againstChlamydia trachomatis infection. However, DNA immunization alone did not generate immune responses or protection as great as that induced by using live organisms. In this study, we evaluated the immunologic effects of a combinational vaccination approach usingC. trachomatis mouse pneumonitis (MoPn) major outer membrane protein (MOMP) DNA priming followed by boosting with immune-stimulating complexes (ISCOM) of MOMP protein (MOMP ISCOM) for protection of BALB/c mice against MoPn lung infection. Substantially better protection to challenge infection was observed in mice given combinational vaccination compared with mice given MOMP ISCOM immunization alone, and the protection approximated that induced by live organisms. Enhanced protection was correlated with stronger delayed-type hypersensitivity, higher levels of gamma interferon production, and increased immunoglobulin A antibody responses in lung homogenates. The results indicate that DNA priming followed by ISCOM protein boosting may be useful in designing a fully protective chlamydial vaccine.

Induction of immune responses by purified outer membrane protein complexes from Neisseria meningitidis

Vaccine ◽  
2012 ◽  
Vol 30 (13) ◽  
pp. 2387-2395 ◽  
Author(s):  
J. Marzoa ◽  
S. Sánchez ◽  
L. Costoya ◽  
E. Diéguez-Casal ◽  
P. Freixeiro ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Immune Responses ◽  
Neisseria Meningitidis ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Protein Complexes ◽  
Membrane Protein Complexes
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