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Protective Immunity in Mice Immunized With P. vivax MSP119-Based Formulations and Challenged With P. berghei Expressing PvMSP119.

ABSTRACT: The lack of continuous in vitro cultures has been an obstacle delaying pre-clinical testing of Plasmodium vivax vaccine formulations based on known antigens. In this study, we generated a model to test available formulations based on the P. vivax MSP119 antigen. The Plasmodium berghei strains ANKA and NK65 were modified to express PvMSP119 instead of the endogenous PbMSP119. The hybrid parasites were used to challenge C57BL/6 or BALB/c mice immunized with PvMSP119-based vaccine formulations. The PvMSP119 was correctly expressed in the P. berghei hybrid mutant lines as confirmed by immunofluorescence using anti-PvMSP119 monoclonal antibodies and by Western blot. Replacement of the PbMSP119 by the PvMSP119 had no impact on asexual growth in vivo. High titers of specific antibodies to PvMSP119 were not sufficient to control initial parasitemia in the immunized mice, but late parasitemia control and a balanced inflammatory process protected these mice from dying, suggesting that an established immune response to PvMSP119 in this model can help immunity mounted later during infection.

SUBMITTER: Dobrescu I

PROVIDER: S-EPMC7045055 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Protective Immunity in Mice Immunized With P. vivax MSP119-Based Formulations and Challenged With P. berghei Expressing PvMSP119.

Dobrescu Irina I de Camargo Tarsila Mendes TM Gimenez Alba Marina AM Murillo Oscar O Amorim Kelly Nazaré da Silva KNDS Marinho Claudio Romero Farias CRF Soares Irene Silva IS Boscardin Silvia Beatriz SB Bargieri Daniel Youssef DY

Frontiers in immunology 20200219

The lack of continuous in vitro cultures has been an obstacle delaying pre-clinical testing of Plasmodium vivax vaccine formulations based on known antigens. In this study, we generated a model to test available formulations based on the P. vivax MSP119 antigen. The Plasmodium berghei strains ANKA and NK65 were modified to express PvMSP119 instead of the endogenous PbMSP119. The hybrid parasites were used to challenge C57 ...[more]

PMID: 32153555

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Project description:BACKGROUND: Influenza virus undergoes constant antigenic evolution, and therefore influenza vaccines must be reformulated each year. Time is necessary to produce a vaccine that is antigenically matched to a pandemic strain. A goal of many research works is to produce universal vaccines that can induce protective immunity to influenza A viruses of various subtypes. Despite intensive studies, the precise mechanisms of heterosubtypic immunity (HSI) remain ambiguous. METHOD: In this study, mice were vaccinated with recombinant virus vaccine (rL H5), in which the hemagglutinin (HA) gene of influenza A/H5N1 virus was inserted into the LaSota Newcastle disease virus (NDV) vaccine strain. Following a challenge with influenza A/H1N1 virus, survival rates and lung index of mice were observed. The antibodies to influenza virus were detected using hemagglutination inhibition (HI). The lung viral loads, lung cytokine levels and the percentages of both IFN-?+CD4+ and IFN-?+CD8+ T cells in spleen were detected using real-time RT-PCR, ELISA and flow cytometry respectively. RESULTS: In comparison with the group of mice given phosphate-buffered saline (PBS), the mice vaccinated with rL H5 showed reductions in lung index and viral replication in the lungs after a challenge with influenza A/H1N1 virus. The antibody titer in group 3 (H1N1-H1N1) was significantly higher than that in other groups which only low levels of antibody were detected. IFN-? levels increased in both group 1 (rL H5-H1N1) and group 2 (rL H5?+?IL-2-H1N1). And the IFN-? level of group 2 was significantly higher than that of group 1. The percentages of both IFN-?+CD4+ and IFN-?+CD8+ T cells in group 1 (rL H5-H1N1) and group 2 (rL H5?+?IL-2-H1N1) increased significantly, as measured by flow cytometry. CONCLUSION: After the mice were vaccinated with rL H5, cross-protective immune response was induced, which was against heterosubtypic influenza A/H1N1 virus. To some extent, cross-protective immune response can be enhanced by IL-2 as an adjuvant. Cellular immune responses may play an important role in HSI against influenza virus.

Project description:Immunization of BALB/c mice with a recombinant adenovirus expressing Mycobacterium tuberculosis (M. tuberculosis) antigen 85A (Ad85A) protects against aerosol challenge with M. tuberculosis only when it is administered intra-nasally (i.n.). Immunization with Ad85A induces a lung-resident population of activated CD8 T cells that is antigen dependent, highly activated and mediates protection by early inhibition of M. tuberculosis growth. In order to determine why the i.n. route is so effective compared to parenteral immunization, we used microarray analysis to compare gene expression profiles of pulmonary and splenic CD8 T cells after i.n. or intra-dermal (i.d.) immunization.Total RNA from CD8 T cells was isolated from lungs or spleens of mice immunized with Ad85A by the i.n. or i.d. route. The gene profiles generated from each condition were compared. Statistically significant (p ? 0.05) differentially expressed genes were analyzed to determine if they mapped to particular molecular functions, biological processes or pathways using Gene Ontology and Panther DB mapping tools.CD8 T cells from lungs of i.n. immunized mice expressed a large number of chemokines chemotactic for resting and activated T cells as well as activation and survival genes. Lung lymphocytes from i.n. immunized mice also express the chemokine receptor gene Cxcr6, which is thought to aid long-term retention of antigen-responding T cells in the lungs. Expression of CXCR6 on CD8 T cells was confirmed by flow cytometry.Our microarray analysis represents the first ex vivo study comparing gene expression profiles of CD8 T cells isolated from distinct sites after immunization with an adenoviral vector by different routes. It confirms earlier phenotypic data indicating that lung i.n. cells are more activated than lung i.d. CD8 T cells. The sustained expression of chemokines and activation genes enables CD8 T cells to remain in the lungs for extended periods after i.n. immunization. This may account for the early inhibition of M. tuberculosis growth observed in Ad85A i.n. immunized mice and explain the effectiveness of i.n. compared to parenteral immunization with this viral vector.

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Protective Immunity in Mice Immunized With P. vivax MSP119-Based Formulations and Challenged With P. berghei Expressing PvMSP119.

Publications

Protective Immunity in Mice Immunized With <i>P. vivax</i> MSP1<sub>19</sub>-Based Formulations and Challenged With <i>P. berghei</i> Expressing <i>Pv</i>MSP1<sub>19</sub>.

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