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Membrane Microvesicles as Potential Vaccine Candidates.

ABSTRACT: The prevention and control of infectious diseases is crucial to the maintenance and protection of social and public healthcare. The global impact of SARS-CoV-2 has demonstrated how outbreaks of emerging and re-emerging infections can lead to pandemics of significant public health and socio-economic burden. Vaccination is one of the most effective approaches to protect against infectious diseases, and to date, multiple vaccines have been successfully used to protect against and eradicate both viral and bacterial pathogens. The main criterion of vaccine efficacy is the induction of specific humoral and cellular immune responses, and it is well established that immunogenicity depends on the type of vaccine as well as the route of delivery. In addition, antigen delivery to immune organs and the site of injection can potentiate efficacy of the vaccine. In light of this, microvesicles have been suggested as potential vehicles for antigen delivery as they can carry various immunogenic molecules including proteins, nucleic acids and polysaccharides directly to target cells. In this review, we focus on the mechanisms of microvesicle biogenesis and the role of microvesicles in infectious diseases. Further, we discuss the application of microvesicles as a novel and effective vaccine delivery system.

SUBMITTER: Shkair L

PROVIDER: S-EPMC7865840 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Membrane Microvesicles as Potential Vaccine Candidates.

Shkair Layaly L Garanina Ekaterina E EE Stott Robert J RJ Foster Toshana L TL Rizvanov Albert A AA Khaiboullina Svetlana F SF

International journal of molecular sciences 20210124 3

The prevention and control of infectious diseases is crucial to the maintenance and protection of social and public healthcare. The global impact of SARS-CoV-2 has demonstrated how outbreaks of emerging and re-emerging infections can lead to pandemics of significant public health and socio-economic burden. Vaccination is one of the most effective approaches to protect against infectious diseases, and to date, multiple vaccines have been successfully used to protect against and eradicate both vir ...[more]

PMID: 33498909

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Project description:Pmps (Polymorphic Membrane Proteins) are a group of membrane bound surface exposed chlamydial proteins that have been characterized as autotransporter adhesins and are important in the initial phase of chlamydial infection. These proteins all contain conserved GGA (I, L, V) and FxxN tetrapeptide motifs in the N-terminal portion of each protein. All chlamydial species express Pmps. Even in the chlamydia-related bacteria Waddlia chondrophila, a Pmp-like adhesin has been identified, demonstrating the importance of Pmps in Chlamydiales biology. Chlamydial species vary in the number of pmp genes and their differentially regulated expression during the infectious cycle or in response to stress. Studies have also demonstrated that Pmps are able to induce innate immune functional responses in infected cells, including production of IL-8, IL-6 and MCP-1, by activating the transcription factor NF-κB. Human serum studies have indicated that although anti-Pmp specific antibodies are produced in response to a chlamydial infection, the response is variable depending on the Pmp protein. In C. trachomatis, PmpB, PmpC, PmpD and PmpI were the proteins eliciting the strongest immune response among adolescents with and without pelvic inflammatory disease (PID). In contrast, PmpA and PmpE elicited the weakest antibody response. Interestingly, there seems to be a gender bias for Pmp recognition with a stronger anti-Pmp reactivity in male patients. Furthermore, anti-PmpA antibodies might contribute to adverse pregnancy outcomes, at least among women with PID. In vitro studies indicated that dendritic cells infected with C. muridarum were able to present PmpG and PmpF on their MHC class II receptors and T cells were able to recognize the MHC class-II bound peptides. In addition, vaccination with PmpEFGH and Major Outer Membrane Protein (MOMP) significantly protected mice against a genital tract C. muridarum infection, suggesting that Pmps may be an important component of a multi-subunit chlamydial vaccine. Thus, Pmps might be important not only for the pathogenesis of chlamydial infection, but also as potential candidate vaccine proteins.

Project description:BackgroundChagas disease, caused by Trypanosoma cruzi, is endemic in Latin America and an emerging infectious disease in the US and Europe. We have shown TcG1, TcG2, and TcG4 antigens elicit protective immunity to T. cruzi in mice and dogs. Herein, we investigated antigenicity of the recombinant proteins in humans to determine their potential utility for the development of next generation diagnostics for screening of T. cruzi infection and Chagas disease.Methods and resultsSera samples from inhabitants of the endemic areas of Argentina-Bolivia and Mexico-Guatemala were analyzed in 1(st)-phase for anti-T. cruzi antibody response by traditional serology tests; and in 2(nd)-phase for antibody response to the recombinant antigens (individually or mixed) by an ELISA. We noted similar antibody response to candidate antigens in sera samples from inhabitants of Argentina and Mexico (n=175). The IgG antibodies to TcG1, TcG2, and TcG4 (individually) and TcG(mix) were present in 62-71%, 65-78% and 72-82%, and 89-93% of the subjects, respectively, identified to be seropositive by traditional serology. Recombinant TcG1- (93.6%), TcG2- (96%), TcG4- (94.6%) and TcG(mix)- (98%) based ELISA exhibited significantly higher specificity compared to that noted for T. cruzi trypomastigote-based ELISA (77.8%) in diagnosing T. cruzi-infection and avoiding cross-reactivity to Leishmania spp. No significant correlation was noted in the sera levels of antibody response and clinical severity of Chagas disease in seropositive subjects.ConclusionsThree candidate antigens were recognized by antibody response in chagasic patients from two distinct study sites and expressed in diverse strains of the circulating parasites. A multiplex ELISA detecting antibody response to three antigens was highly sensitive and specific in diagnosing T. cruzi infection in humans, suggesting that a diagnostic kit based on TcG1, TcG2 and TcG4 recombinant proteins will be useful in diverse situations.

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Membrane Microvesicles as Potential Vaccine Candidates.

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Membrane Microvesicles as Potential Vaccine Candidates.

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