Mucosal HIV-1 pox virus prime-boost immunization induces high-avidity CD8+ T cells with regime-dependent cytokine/granzyme B profiles.

Ranasinghe, C.; Turner, S. J.; McArthur, C.; Sutherland, Duncan B.; Kim, J.-H.; Doherty, P. C.; Ramshaw, I. A.

doi:10.4049/jimmunol.178.12.8221

Cited by 22 publications

(60 citation statements)

References 39 publications

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“…5e and 5f). Thus, overall it appears that the heterologous prime-boost vaccination regime generates the best HIV-gag peptide CTL response, both in terms of magnitude and avidity, a finding consistent with that previously reported (29).…”

Section: Use Of a 216 Fta To Assess The Killing Efficiency Of Ctls Insupporting

confidence: 80%

Fluorescent target array killing assay: A multiplex cytotoxic T‐cell assay to measure detailed T‐cell antigen specificity and avidity in vivo

et al. 2012

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Here we describe a multiplex, fluorescence‐based, in vivo cytotoxic T‐cell assay using the three vital dyes carboxyfluorescein diacetate succinimidyl ester, cell trace violet, and cell proliferation dye efluor 670. When used to label cells in combination, these dyes can discriminate >200 different target cell populations in the one animal due to each target population having a unique fluorescence signature based on fluorescence intensity and the different emission wavelengths of the dyes. This allows the simultaneous measurement of the in vivo killing of target cells pulsed with numerous peptides at different concentrations and the inclusion of many replicates. This fluorescent target array killing assay can be used to measure the fine antigen specificity and avidity of polyclonal cytotoxic T‐cell responses in vivo, immunological parameters that were previously impossible to monitor. © 2012 International Society for Advancement of Cytometry

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Section: Use Of a 216 Fta To Assess The Killing Efficiency Of Ctls Insupporting

confidence: 80%

Fluorescent target array killing assay: A multiplex cytotoxic T‐cell assay to measure detailed T‐cell antigen specificity and avidity in vivo

et al. 2012

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“…A subsequent study reported that mucosally targeted immunization (IN/IM and IN/IN) induced CTLs of higher avidity, as determined by a tetramer dissociation assay, than a peripheral vaccination strategy such as IM/IM. 99 In an SIV challenge experiment in rhesus macaques, intranasal vaccination has shown the capacity to reduce virus replication, but not virus acquisition. 100 Hence, the number of low-dose repeated SIV challenges needed for infection in animals receiving DNA (SIV + IL-2 + IL-15) prime followed by MVA (SIV gag/pol/nef) boost intranasally was similar to those in the intramuscular and the unvaccinated control groups.…”

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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“…Samples were run on an ABI PRISM 7700 sequence detection system (Applied Biosystems) and analyzed using SDS 1.9.1 software. Fold increases in mRNA were calculated as described previously (35).…”

Section: Real-time Pcrmentioning

confidence: 99%

Differential Effects of the Type I Interferons α4, β, and ε on Antiviral Activity and Vaccine Efficacy

Day

Ramshaw

Ramsay

et al. 2008

The Journal of Immunology

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The type I IFNs exert a range of activities that include antiviral, antiproliferative, and immunomodulatory effects. To study this further, we have constructed recombinant vaccinia viruses expressing HIV or hemagglutinin (HA) Ags along with murine type I IFNs, IFN-α4 (HA-VV-IFN-α4), IFN-β (HA-VV-IFN-β), or IFN-ε (HIV-VV-IFN-ε), a recently discovered member of this family. Our aims were to characterize IFN-ε functionality as a type I IFN and also to study the biological properties of these factors toward the development of safer and more effective vector-based vaccines. HIV-VV-IFN-ε and HA-VV-IFN-β grew to lower titers than did their parental controls in murine cell lines. In vivo, however, HIV-VV-IFN-ε growth was not attenuated, while IFN-β demonstrated potent local antiviral activity with no replication of HA-VV-IFN-β detected. Flow cytofluorometric analysis of B lymphocytes incubated with virally encoded IFN-ε showed up-regulation of activation markers CD69 and CD86, while RT-PCR of IFN-ε-treated cells revealed that gene expression levels of antiviral proteins were elevated, indicating the induction of an antiviral state. The use of these constructs in a poxvirus prime-boost immunization regime led to robust humoral and cellular immune responses against the encoded Ags, despite the lack of replication in the case of HA-VV-IFN-β. Thus, coexpression of these factors may be beneficial in the design of safer vector-based vaccines. Our data also indicate that while IFN-ε exhibits certain biological traits similar to other type I IFNs, it may also have a specific role in mucosal immune regulation that is quite distinct.

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Mucosal HIV-1 pox virus prime-boost immunization induces high-avidity CD8+ T cells with regime-dependent cytokine/granzyme B profiles.

Cited by 22 publications

References 39 publications

Fluorescent target array killing assay: A multiplex cytotoxic T‐cell assay to measure detailed T‐cell antigen specificity and avidity in vivo

Fluorescent target array killing assay: A multiplex cytotoxic T‐cell assay to measure detailed T‐cell antigen specificity and avidity in vivo

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

Differential Effects of the Type I Interferons α4, β, and ε on Antiviral Activity and Vaccine Efficacy

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