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Journal articleLi C, Jin W, Du T, et al., 2014,
Binding of HIV-1 virions to α4β 7 expressing cells and impact of antagonizing α4β 7 on HIV-1 infection of primary CD4+ T cells.
, Virol Sin, Vol: 29, Pages: 381-392HIV-1 envelope glycoprotein is reported to interact with α4β7, an integrin mediating the homing of lymphocytes to gut-associated lymphoid tissue, but the significance of α4β7 in HIV-1 infection remains controversial. Here, using HIV-1 strain BaL, the gp120 of which was previously shown to be capable of interacting with α4β7, we demonstrated that α4β7 can mediate the binding of whole HIV-1 virions to α4β7-expressing transfectants. We further constructed a cell line stably expressing α4β7 and confirmed the α4β7-mediated HIV-1 binding. In primary lymphocytes with activated α4β7 expression, we also observed significant virus binding which can be inhibited by an anti-α4β7 antibody. Moreover, we investigated the impact of antagonizing α4β7 on HIV-1 infection of primary CD4(+) T cells. In α4β7-activated CD4(+) T cells, both anti-α4β7 antibodies and introduction of short-hairpin RNAs specifically targeting α4β7 resulted in a decreased HIV-1 infection. Our findings indicate that α4β7 may serve as an attachment factor at least for some HIV-1 strains. The established approach provides a promising means for the investigation of other viral strains to understand the potential roles of α4β7 in HIV-1 infection.
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Book chapterTregoning JS, Kinnear E, 2014,
Using Plasmids as DNA Vaccines for Infectious Diseases.
, Plasmids: Biology and Impact in Biotechnology and Discovery, Publisher: ASMscience, ISBN: 9781555818975DNA plasmids can be used to induce a protective (or therapeutic) immune response by delivering genes encoding vaccine antigens. That naked DNA (without the refinement of coat proteins or host evasion systems) can cross from outside the cell into the nucleus and be expressed is particularly remarkable given the sophistication of the immune system in preventing infection by pathogens. As a result of the ease, low cost, and speed of custom gene synthesis, DNA vaccines dangle a tantalizing prospect of the next wave of vaccine technology, promising individual designer vaccines for cancer or mass vaccines with a rapid response time to emerging pandemics. There is considerable enthusiasm for the use of DNA vaccination as an approach, but this enthusiasm should be tempered by the successive failures in clinical trials to induce a potent immune response. The technology is evolving with the development of improved delivery systems that increase expression levels, particularly electroporation and the incorporation of genetically encoded adjuvants. This review will introduce some key concepts in the use of DNA plasmids as vaccines, including how the DNA enters the cell and is expressed, how it induces an immune response, and a summary of clinical trials with DNA vaccines. The review also explores the advances being made in vector design, delivery, formulation, and adjuvants to try to realize the promise of this technology for new vaccines. If the immunogenicity and expression barriers can be cracked, then DNA vaccines may offer a step change in mass vaccination.
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Journal articleStieh D, King DF, Klein K, et al., 2014,
Aggregate complexes of HIV-1 induced by multimeric antibodies.
, Retrovirology, Vol: 11, ISSN: 1742-4690BackgroundAntibody mediated viral aggregation may impede viral transfer across mucosal surfaces by hindering viral movement in mucus, preventing transcytosis, or reducing inter-cellular penetration of epithelia thereby limiting access to susceptible mucosal CD4 T cells and dendritic cells. These functions may work together to provide effective immune exclusion of virus from mucosal tissue; however little is known about the antibody characteristics required to induce HIV aggregation. Such knowledge may be critical to the design of successful immunization strategies to facilitate viral immune exclusion at the mucosal portals of entry.ResultsThe potential of neutralizing and non-neutralizing IgG and IgA monoclonals (mAbs) to induce HIV-1 aggregation was assessed by Dynamic light scattering (DLS). Although neutralizing and non-neutralizing IgG mAbs and polyclonal HIV-Ig efficiently aggregated soluble Env trimers, they were not capable of forming viral aggregates. In contrast, dimeric (but not monomeric) IgA mAbs induced stable viral aggregate populations that could be separated from uncomplexed virions. Epitope specificity influenced both the degree of aggregation and formation of higher order complexes by dIgA. IgA purified from serum of uninfected RV144 vaccine trial responders were able to efficiently opsonize viral particles in the absence of significant aggregation, reflective of monomeric IgA.ConclusionsThese results collectively demonstrate that dIgA is capable of forming stable viral aggregates providing a plausible basis for testing the effectiveness of aggregation as a potential protection mechanism at the mucosal portals of viral entry.
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Conference paperKing DFL, McKay PF, Mann JFS, et al., 2014,
Single and Combined Vaccination Modalities Result in Distinct Immunological Profiles in HIV-1 gp140-immunised Mice
, Symposium on HIV Research for Prevention (HIV R4P), Publisher: MARY ANN LIEBERT, INC, Pages: A244-A244, ISSN: 0889-2229 -
Conference paperMcKay PF, King DFL, Mann JFS, et al., 2014,
Combinations of TLR4 and TLR7/8 Adjuvants Administered via the ID or IN Routes Generate Different Vaccine Antigen-specific Immune Outcomes in Minipigs
, Symposium on HIV Research for Prevention (HIV R4P), Publisher: MARY ANN LIEBERT, INC, Pages: A194-A195, ISSN: 0889-2229 -
Journal articleArakelyan A, King D, Grivel J-C, et al., 2014,
Heterogeneous Conformation of HIV-1 Envelopes on Individual Virions
, AIDS RESEARCH AND HUMAN RETROVIRUSES, Vol: 30, Pages: A78-A79, ISSN: 0889-2229 -
Journal articleOkala SG, King DF, Rogers PM, et al., 2014,
Antibody Isotypes Differ in their Capacity to Bind, Capture and Aggregate HIV-1 Virions
, AIDS RESEARCH AND HUMAN RETROVIRUSES, Vol: 30, Pages: A64-A64, ISSN: 0889-2229 -
Journal articleLe Grand R, Bosquet NN, Dispinseri S, et al., 2014,
Microbicide-vaccine Combination Provides Significant Protection against Vaginal SHIV-162P3 Challenge in Cynomolgous Monkeys
, AIDS RESEARCH AND HUMAN RETROVIRUSES, Vol: 30, Pages: A26-A26, ISSN: 0889-2229 -
Journal articleCheeseman HM, Klein K, Evans A, et al., 2014,
Functional Assessment of Antibody Activity in Mucosal Tissue Explant and Cellular Inhibition Assays
, AIDS RESEARCH AND HUMAN RETROVIRUSES, Vol: 30, Pages: A230-A230, ISSN: 0889-2229 -
Journal articleCope AV, Moog C, Shattock RJ, et al., 2014,
A Phase I Clinical Trial with a Novel gp41 HIV Vaccine (EN41-FPA2) in Healthy Female Volunteers: A Mucosal Prime and Intramuscular Boost Regimen
, AIDS RESEARCH AND HUMAN RETROVIRUSES, Vol: 30, Pages: A187-A188, ISSN: 0889-2229
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