HIV vaccines: brief review and discussion of future directions

Slobod, Karen S.; Bonsignori, Mattia; Brown, Scott A.; Zhan, Xiaoyan; Stambas, John; Hurwitz, Julia L.

doi:10.1586/14760584.4.3.305

Cited by 11 publications

(9 citation statements)

References 94 publications

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“…It is relatively well established that the sole use of monomeric gp120 as immunisation antigen is not optimal for the generation of neutralising antibodies (reviewed in (28)). In the first human trial no protection was obtained (29) and primate immunisation experiments have been relatively unsuccessful although low‐level nabs to heterologous isolates have been demonstrated (19).…”

Section: Resultsmentioning

confidence: 99%

Immune response in rhesus macaques after mixed modality immunisations with DNA, recombinant adenovirus and recombinant gp120 from human immunodeficiency virus type 1

Vinner

Therrien

Wee

et al. 2006

APMIS

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The establishment of effective regimens for a vaccine against human immunodeficiency virus type 1 (HIV-1) is urgently needed. In the present study we have produced HIV-1 gp120 from a vaccine-relevant primary R5 isolate in recombinant vaccinia (rVV)-infected Vero cells. We have investigated the effect of boosting with this protein in mixed modality immunisations of rhesus macaques following different immunisation. As reported earlier, animals were primed with codon-optimised HIV-1(BX08)env DNA delivered as plasmid or as replication-deficient recombinant human adenovirus type 5 (rAd5), which both induced specific antibody and cellular immune responses (1). Boosting with rAd5 temporarily had increased the anti-gp120 antibody titres approximately 1 log (rAd5+rAd5) or 3 log (DNA+rAd5) (1). However, secondary rAd5 boosting showed less effect due to the induced vector-specific immunity. To further boost the antibody response, the rgp120(BX08) was injected with Quadri A saponin adjuvant. The protein boosting resulted in a 1-2 log antibody increase and also boosting of the cell-mediated immune response. Neutralising antibodies to the heterologous HIV-1(MN) were detected; however, neutralising antibodies to the primary HIV-1(Bx08) isolate were seen only transiently after rAd5 but not the rgp120 immunisation. It is concluded that the rgp120(Bx08) reagent from rVV-infected Vero cells is functional and immunogenic in macaques, inducing both antibody and cellular immunity. The rgp120(Bx08) is a relevant model antigen that may be used to boost antibody and cellular immunity in mixed modality vaccine regimens against HIV-1 in higher animals.

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Section: Resultsmentioning

confidence: 99%

Immune response in rhesus macaques after mixed modality immunisations with DNA, recombinant adenovirus and recombinant gp120 from human immunodeficiency virus type 1

Vinner

Therrien

Wee

et al. 2006

APMIS

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“…Of the three stages, the final fusion step has already been exploited therapeutically, and also several strategies are under development for prophylactic vaccines that aim to block the first step (52)(53)(54). From a biological point of view, the second step, that of co-receptor usage, could be considered as a potential therapeutic target although inference of the physiological function of these chemokine receptors by attempting to block viral access may be detrimental, and therefore toxic to the patient.…”

Section: Hiv-1 Cell Attachment and Entry Processmentioning

confidence: 99%

HIV-1 infection: Is it time to reconsider our concepts?

Krambovitis¹,

Spandidos²

2006

Int J Mol Med

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The long asymptomatic phase of HIV infection is critical in the progression to AIDS. It probably reflects an ancestral relationship with lentiviruses stemming from the primate-simian immunodeficiency virus evolutionary pathway leading to an idiosyncratic immune tolerance, which needs to be understood if effective vaccines are to be rationally designed. The majority of CD4 + T cells that die due to HIV-1 in the asymptomatic phase are not infected with the virus. Transmission of the predominant HIV-1 R5 variants to T cells is mediated by infected monocyte-derived macrophages. The two cell populations come into intimate contact mainly in the lymph nodes during antigen presentation where there is also active viral replication. We propose that HIV exploits antigen presentation to access target T cells and evade immune surveillance. This is achieved at the assembly point of an immunological synapse between an antigen presenting, HIV-1infected macrophage and a responding effector/memory CD4 + T cell. Viral envelope gp120 glycoproteins proximal to MHC II molecules cross-link with T cell CD4 molecules, thus establishing a supra molecular immuno-viral synapse. The interaction results in conformational changes of gp120 exposing its V3 domain. Ionic interaction of this domain with the synapse-recruited chemokine receptor CCR5 dimerizes the receptor triggering intracellular signals that contribute to T cell receptor transactivation pathways and subsequent enhancement of T cell activation. HIV-downregulated MHC II gives weak immune complexes. Disruption of the immunoviral synapse before completion of cell entry is a frequent outcome condemning the responding T cell to a premature activation-induced T cell death. Information on the assembly, mechanistic and functional interactions at the immuno-viral synapses may well assist in elucidating new strategies to combat HIV infection. Contents 1. Introduction 2. Is AIDS associated with the evolution of common viral ancestors to HIV? 3. AIDS: a cytopathic viral disease or an immune dysfunction caused by the presence of HIV-1? 4. The antigen activation CD4 + T cell death model 5. HIV-1 cell attachment and entry process 6. Is HIV-1 attachment facilitated by immuno-viral synapses? 7. Proposed theoretical model of R5 HIV-1 cell attachment and concluding remarks

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“…Therefore, there are still important regional differences that should be solved [ 2 , 3 ]. On the other hand, the development of an effective HIV vaccine is still under progress with a number of failures [ 4 ] because of the high rate of evolution of HIV-1 [ 5 , 6 ]. As a consequence, up to date the only treatment for HIV-1 is the antiretroviral drug therapy.…”

Section: Introductionmentioning

confidence: 99%

Genetic Consequences of Antiviral Therapy on HIV-1

Arenas

2015

Computational and Mathematical Methods in Medicine

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A variety of enzyme inhibitors have been developed in combating HIV-1, however the fast evolutionary rate of this virus commonly leads to the emergence of resistance mutations that finally allows the mutant virus to survive. This review explores the main genetic consequences of HIV-1 molecular evolution during antiviral therapies, including the viral genetic diversity and molecular adaptation. The role of recombination in the generation of drug resistance is also analyzed. Besides the investigation and discussion of published works, an evolutionary analysis of protease-coding genes collected from patients before and after treatment with different protease inhibitors was included to validate previous studies. Finally, the review discusses the importance of considering genetic consequences of antiviral therapies in models of HIV-1 evolution that could improve current genotypic resistance testing and treatments design.

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HIV vaccines: brief review and discussion of future directions

Cited by 11 publications

References 94 publications

Immune response in rhesus macaques after mixed modality immunisations with DNA, recombinant adenovirus and recombinant gp120 from human immunodeficiency virus type 1

Immune response in rhesus macaques after mixed modality immunisations with DNA, recombinant adenovirus and recombinant gp120 from human immunodeficiency virus type 1

HIV-1 infection: Is it time to reconsider our concepts?

Genetic Consequences of Antiviral Therapy on HIV-1

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