The Th1 immune response against HIV‐1 Gag p24‐derived peptides in mice expressing HLA‐A02.01 and HLA‐DR1

Pajot, Anthony; Schnuriger, Aurélie; Moris, Arnaud; Rodallec, Audrey; Ojcius, David M.; Autran, Brigitte; Lefrère, François; Lone, Yu Chun

doi:10.1002/eji.200636819

Cited by 6 publications

(7 citation statements)

References 28 publications

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“…34,35 Furthermore, studies show that the lower percentage of CD8 C T lymphocytes does not preclude the use of HLA-A2/DR1 Tg mice for studies of immune responses to pathogens such as HBV and HIV. 34,36 Interesting, it is now well documented by several comparative studies that transgenic HLA class I molecules in chimeric monochain form are superior than traditional transgenic HLA class I molecule mice to induce more efficient T cell responses, even the number of CD8 T cell is lower. 37,38 We also confirmed that HLA-A11/DR1 Tg mice mount efficient and functional humoral and cellular immune responses to a recombinant HBV vaccine and a recombinant HIV-1 protein, and especially mount the specific A11-restricted cellular immune response to a recombinant HIV-1 protein.…”

Section: Discussionmentioning

confidence: 99%

Generation of human MHC (HLA-A11/DR1) transgenic mice for vaccine evaluation

Zeng

Gao

Zhao

et al. 2015

Human Vaccines & Immunotherapeutics

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The rapid occurrence of emerging infectious diseases demonstrates an urgent need for a new preclinical experimental model that reliably replicates human immune responses. Here, a new homozygous humanized human leukocyte antigen (HLA)-A11/DR1 transgenic mouse (HLA-A11(+/+)/DR01(+/+)/H-2-β2m(-/-)/IAβ(-/-)) was generated by crossing HLA-A11 transgenic (Tg) mice with HLA-A2(+/+)/DR01(+/+)/H-2-β2m(-/-)/IAβ(-/-) mice. The HLA-A11-restricted immune response of this mouse model was then examined. HLA-A11 Tg mice expressing a chimeric major histocompatibility complex (MHC) molecule comprising the α1, α2, and β2m domains of human HLA-A11 and the α3 transmembrane and cytoplasmic domains of murine H-2D(b) were generated. The correct integration of HLA-A11 and HLA-DR1 into the genome of the HLA-A11/DR1 Tg mice (which lacked the expression of endogenous H-2-I/II molecules) was then confirmed. Immunizing mice with a recombinant HBV vaccine or a recombinant HIV-1 protein resulted in the generation of IFN-γ-producing cytotoxic T lymphocyte (CTL) and antigen-specific antibodies. The HLA-A11-restricted CTL response was directed at HLA immunodominant epitopes. These mice represent a versatile animal model for studying the immunogenicity of HLA CTL epitopes in the absence of a murine MHC response. The established animal model will also be useful for evaluating and optimizing T cell-based vaccines and for studying differences in antigen processing between mice and humans.

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Section: Discussionmentioning

confidence: 99%

Generation of human MHC (HLA-A11/DR1) transgenic mice for vaccine evaluation

Zeng

Gao

Zhao

et al. 2015

Human Vaccines & Immunotherapeutics

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“…Even in this case, expression of transgenic HLA-A2.1 molecule led to an increase in the size of the peripheral CD8+ T cell population, which reached 2–3% of the total splenocytes in HLA-A2/DR1 mice, compared to 0.6–1% in β2m-KO MHC-I deficient mice [12]. Furthermore, this phenomenon had been discussed and several studies on HBV and HIV proved that the low percentage for CD8+ T cell doesn't significantly affect the usage of HLA-A2/DR1 mice in immunological analysis [41], [42].…”

Section: Discussionmentioning

confidence: 99%

Development of a Humanized HLA-A2.1/DP4 Transgenic Mouse Model and the Use of This Model to Map HLA-DP4-Restricted Epitopes of HBV Envelope Protein

Xiao

Pajot

et al. 2012

PLoS ONE

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A new homozygous humanized transgenic mouse strain, HLA-A2.1+/+HLA-DP4+/+ hCD4+/+mCD4−/−IAβ−/−β2m−/− (HLA-A2/DP4), was obtained by crossing the previously characterized HLA-A2+/+β2m−/− (A2) mouse and our previously created HLA-DP4+/+ hCD4+/+mCD4−/−IAβ−/− (DP4) mouse. We confirmed that the transgenes (HLA-A2, HLA-DP4, hCD4) inherited from the parental A2 and DP4 mice are functional in the HLA-A2/DP4 mice. After immunizing HLA-A2/DP4 mice with a hepatitis B DNA vaccine, hepatitis B virus-specific antibodies, HLA-A2-restricted and HLA-DP4-restricted responses were observed to be similar to those in naturally infected humans. Therefore, the present study demonstrated that HLA-A2/DP4 transgenic mice can faithfully mimic human cellular responses. Furthermore, we reported four new HLA-DP4-restricted epitopes derived from HBsAg that were identified in both vaccinated HLA-A2/DP4 mice and HLA-DP4-positive human individuals. The HLA-A2/DP4 mouse model is a promising preclinical animal model carrying alleles present to more than a quarter of the human population. This model should facilitate the identification of novel HLA-A2- and HLA-DP4-restricted epitopes and vaccine development as well as the characterization of HLA-DP4-restricted responses against infection in humans.

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“…Cytokine profile analysis of this candidate vaccine showed that the adjuvanted fusion peptide induced an eightfold increase in the IFN-γ/IL-4 ratio leading to a Th1 cytokine pattern compared to the other groups. The shift to a Th1 immune response plays an important role in viral infections such as HIV-1 and this profile facilitates the induction of cellular immunity against viral pathogens (Cristillo et al, 2006;Pajot et al, 2007;Koopman et al, 2008). Humoral immune response and antibody subtypes specific to p24-Nef fusion peptide were also examined.…”

Section: Discussionmentioning

confidence: 99%

HIV-1 Gag p24-Nef fusion peptide induces cellular and humoral immune response in a mouse model

Mahdavi¹,

Ebtekar²,

Azadmanesh³

et al. 2010

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Many Human immunodeficiency virus (HIV) candidate vaccines have been tested in clinical trials, but none was sufficiently effective in the prevention of HIV infection. A HIV vaccine should induce humoral as well as cell-mediated response, the latter including the cytotoxic CD8+ T lymphocyte (CTL) response. In this study, we immunized BALB/c mice with a purified fusion peptide Gag p24-Nef and evaluated immune responses. As for the cellular responses, the adjuvanted fusion peptide induced lymphocyte proliferation, CTL response, and cytokines IFN-γ and IL-4 in the Th1 pattern. Humoral immune response to the adjuvanted fusion peptide included an increase in IgG antibodies of more IgG2a than IgG1 subtype. These results indicate that the employed HIV-1 peptide construct can elicit both cellular and humoral immune responses in mice. Further studies aimed at memory T cells and other aspects of immune responses are needed before a comprehensive assessment of this candidate vaccine could be provided.

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The Th1 immune response against HIV‐1 Gag p24‐derived peptides in mice expressing HLA‐A02.01 and HLA‐DR1

Cited by 6 publications

References 28 publications

Generation of human MHC (HLA-A11/DR1) transgenic mice for vaccine evaluation

Generation of human MHC (HLA-A11/DR1) transgenic mice for vaccine evaluation

Development of a Humanized HLA-A2.1/DP4 Transgenic Mouse Model and the Use of This Model to Map HLA-DP4-Restricted Epitopes of HBV Envelope Protein

HIV-1 Gag p24-Nef fusion peptide induces cellular and humoral immune response in a mouse model

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