Mucosal and systemic anti-GAG immunity induced by neonatal immunization with HIV LAMP/gag DNA vaccine in mice

Goldoni, Adriana Letícia; Maciel, Milton; Rigato, Paula Ordonhez; Piubelli, Orlando; Brito, Cyro Alves de; Melo, Andréa Barbosa de; Marques, Ernesto T. A.; August, J. Thomas; Duarte, Alberto José da Silva; Sato, Maria Notomi

doi:10.1016/j.imbio.2010.08.007

Cited by 14 publications

(17 citation statements)

References 33 publications

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“…Consistent with this concept, DNA encoding HIV-1 gag fused to lysosome-associated membrane protein (LAMP/gag) delivered intranasally to neonatal mice was shown to elicit IgA, IgG, and IFN-c + T cell responses in the intestines. 95 The conjugation of gag to LAMP modulates the uptake and presentation of gag antigens, enhancing the production of both IgA and IgG in comparison to a pure gag DNA formulation.…”

Section: Intranasal Vaccinationmentioning

confidence: 99%

Induction of Intestinal Immunity by Mucosal Vaccines As a Means of Controlling HIV Infection

Poles

Alvarez²,

Hioe³

2014

AIDS Research and Human Retroviruses

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CD4+ T cells in the mucosa of the gastrointestinal (GI) tract are preferentially targeted and depleted by HIV. As such, the induction of an effective anti-HIV immune response in the mucosa of the GI tract-through vaccination-could protect this vulnerable population of cells. Mucosal vaccination provides a promising means of inducing robust humoral and cellular responses in the GI tract. Here we review data from the literature about the effectiveness of various mucosal vaccination routes-oral (intraintestinal/tonsilar/sublingual), intranasal, and intrarectal-with regard to the induction of immune responses mediated by cytotoxic T cells and antibodies in the GI mucosa, as well as protective efficacy in challenge models. We present data from the literature indicating that mucosal routes have the potential to effectively elicit GI mucosal immunity and protect against challenge. Given their capacity for the induction of anti-HIV immune responses in the GI mucosa, we propose that mucosal routes, including the nonconventional sublingual, tonsilar, and intrarectal routes, be considered for the delivery of the next generation HIV vaccines. However, further studies are necessary to determine the ideal vectors and vaccination regimens for these routes of immunization and to validate their efficacy in controlling HIV infection. HIV Epidemics and Treatment HIV infection has resulted in the death of millions since the early 1980s, and has been responsible for significant morbidity and decline in quality of life for millions more. Each year, an estimated 50,000 people are newly infected with the virus in the United States alone, adding to the 34 million currently living with the virus worldwide.

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Section: Intranasal Vaccinationmentioning

confidence: 99%

Induction of Intestinal Immunity by Mucosal Vaccines As a Means of Controlling HIV Infection

Poles

Alvarez²,

Hioe³

2014

AIDS Research and Human Retroviruses

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“…Targeting of vaccine antigens for optimal epitope processing and presentation is a promising way to enhance the potency of a DNA vaccine [75,163,164]. Goldoni et al studied the immunogenicity of the DNA-vaccine encoding HIV-1 Gag chimeric protein combined with the lysosome-associated membrane protein (LAMP/Gag) [165]. LAMP, specifically associated with immunogens, targets vaccine proteins to lysosomal compartments for degradation and subsequent peptide presentation.…”

Section: Pmhc Multimers and Hiv-1 Vaccine Developmentmentioning

confidence: 99%

“…LAMP, specifically associated with immunogens, targets vaccine proteins to lysosomal compartments for degradation and subsequent peptide presentation. The quantity of H-2Kd/AMQMLKETI pentamer-specific CD8 + T-cells after DNA-vaccination suggested the high efficiency of the LAMP/Gag formulation [165]. Moreover, utilizing HIV-1 Gag H-2Kd/AMQMLKETI pentamers, Rigato et al demonstrated that the LAMP/p55 HIV Gag DNA chimeric vaccine is much more effective in activation of HIV-1-specific CD8 + T-cell responses after immunization in the neonatal period, compared with postnatal vaccination [166].…”

Section: Pmhc Multimers and Hiv-1 Vaccine Developmentmentioning

confidence: 99%

Peptide–MHC multimer-based monitoring of CD8 T-cells in HIV-1 infection and AIDS vaccine development

Reguzova

Karpenko

Mechetina

et al. 2014

Expert Review of Vaccines

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The use of MHC multimers allows precise and direct detecting and analyzing of antigen-specific T-cell populations and provides new opportunities to characterize T-cell responses in humans and animals. MHC-multimers enable us to enumerate specific T-cells targeting to viral, tumor and vaccine antigens with exceptional sensitivity and specificity. In the field of HIV/SIV immunology, this technique provides valuable information about the frequencies of HIV- and SIV-specific CD8(+) cytotoxic T lymphocytes (CTLs) in different tissues and sites of infection, AIDS progression, and pathogenesis. Peptide-MHC multimer technology remains a very sensitive tool in detecting virus-specific T -cells for evaluation of the immunogenicity of vaccines against HIV-1 in preclinical trials. Moreover, it helps to understand how immune responses are formed following vaccination in the dynamics from priming point until T-cell memory is matured. Here we review a diversity of peptide-MHC class I multimer applications for fundamental immunological studies in different aspects of HIV/SIV infection and vaccine development.

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“…Our group has previously studied the LAMP/HIV-1-gag chimeric DNA vaccine in neonate models [12], [13]. The lysosome-associated membrane protein-1 (LAMP-1) is highly expressed by all nucleated cells and is found in the MHC class II-enriched intracellular compartments (MIICs) that are associated with antigen presentation [14].…”

Section: Introductionmentioning

confidence: 99%

“…Intradermal delivery of the LAMP/HIV-1-gag DNA vaccine has been shown to (i) elicit enhanced Ab production, (ii) amplify the anti- Gag CD4+, CD8+ T and B cells responses, and (iii) prolong immunological memory to Gag epitopes in adult mouse and monkey experimental models [14], [15], [16], [12]. Recently, we have shown that mucosal and intradermal immunization of neonates with the LAMP/HIV-1-gag ( LAMP/gag ) construct correlates with strong anti-Gag cellular and humoral immune responses [12], [13].…”

Section: Introductionmentioning

confidence: 99%

Maternal LAMP/p55gagHIV-1 DNA Immunization Induces In Utero Priming and a Long-Lasting Immune Response in Vaccinated Neonates

et al. 2012

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Infants born to HIV-infected mothers are at high risk of becoming infected during gestation or the breastfeeding period. A search is thus warranted for vaccine formulations that will prevent mother-to-child HIV transmission. The LAMP/gag DNA chimeric vaccine encodes the HIV-1 p55gag fused to the lysosome-associated membrane protein-1 (LAMP-1) and has been shown to enhance anti-Gag antibody (Ab) and cellular immune responses in adult and neonatal mice; such a vaccine represents a new concept in antigen presentation. In this study, we evaluated the effect of LAMP/gag DNA immunization on neonates either before conception or during pregnancy. LAMP/gag immunization of BALB/c mice before conception by the intradermal route led to the transfer of anti-Gag IgG1 Ab through the placenta and via breastfeeding. Furthermore, there were an increased percentage of CD4+CD25+Foxp3+T cells in the spleens of neonates. When offspring were immunized with LAMP/gag DNA, the anti-Gag Ab response and the Gag-specific IFN-γ-secreting cells were decreased. Inhibition of anti-Gag Ab production and cellular responses were not observed six months after immunization, indicating that maternal immunization did not interfere with the long-lasting memory response in offspring. Injection of purified IgG in conjunction with LAMP/gag DNA immunization decreased humoral and cytotoxic T-cell responses. LAMP/gag DNA immunization by intradermal injection prior to conception promoted the transfer of Ab, leading to a diminished response to Gag without interfering with the development of anti-Gag T- and B-cell memory. Finally, we assessed responses after one intravenous injection of LAMP/gag DNA during the last five days of pregnancy. The intravenous injection led to in utero immunization. In conclusion, DNA vaccine enconding LAMP-1 with Gag and other HIV-1 antigens should be considered in the development of a protective vaccine for the maternal/fetal and newborn periods.

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Mucosal and systemic anti-GAG immunity induced by neonatal immunization with HIV LAMP/gag DNA vaccine in mice

Cited by 14 publications

References 33 publications

Induction of Intestinal Immunity by Mucosal Vaccines As a Means of Controlling HIV Infection

Induction of Intestinal Immunity by Mucosal Vaccines As a Means of Controlling HIV Infection

Peptide–MHC multimer-based monitoring of CD8 T-cells in HIV-1 infection and AIDS vaccine development

Maternal LAMP/p55gagHIV-1 DNA Immunization Induces In Utero Priming and a Long-Lasting Immune Response in Vaccinated Neonates

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