Polyvalent DNA prime and envelope protein boost HIV‐1 vaccine elicits humoral and cellular responses and controls plasma viremia in rhesus macaques following rectal challenge with an R5 SHIV isolate

Pal, Ranajit; Wang, Shixia; Kalyanaraman, V. S.; Nair, Bindukumar; Whitney, Stephen; Keen, Timothy; Hocker, Lindsey; Hudacik, Lauren; Rose, Nicolas; Cristillo, Anthony D.; Mboudjeka, Innocent; Shen, Siyuan; Wu-Chou, Te-Hui; Montefiori, David C.; Mascola, John R.; Lu, Shan; Markham, Phillip D.

doi:10.1111/j.1600-0684.2005.00120.x

Cited by 53 publications

(47 citation statements)

References 33 publications

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“…Recently, we demonstrated that a DNA prime-protein boost immunization strategy was effective in eliciting humoral and CMI responses in both small animals and non-human primates, including sterilizing immunity in a non-pathogenic SHIV model [16][17][18]. Our preclinical study results also indicated that this combination vaccination approach, but not recombinant protein alone, was effective in eliciting NAbs against primary HIV isolates [19], a finding that has been confirmed subsequently by other independent studies [20][21][22][23][24][25][26].…”

Section: Introductionsupporting

confidence: 75%

“…Multi-gene, polyvalent, DNA prime-protein boost formulation DP6−001 2.1.a. DNA vaccines-The DP6−001 vaccine contains equal amounts of six individual DNA plasmid components utilizing the same vector pSW3891 [17]: five plasmids each encoding a codon-optimized gp120 gene sequence from the following primary HIV-1 Envelope proteins: subtypes A (92UG037.8), B (92US715.6 and Bal), C (96ZM651) and E (93TH976.17) and the sixth plasmid encoding a codon-optimized gag gene from subtype C (96ZM651) as previously described [28]. The cGMP plasmid DNA for this Phase I clinical trial was produced by Althea Technology (San Diego, CA).…”

Section: Methodsmentioning

confidence: 99%

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Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime–protein boost HIV-1 vaccine in healthy human volunteers

Wang

Kennedy

West

et al. 2008

Vaccine

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124

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An optimally effective AIDS vaccine would likely require the induction of both neutralizing antibody and cell-mediated immune responses, which has proven difficult to obtain in previous clinical trials. Here we report the induction of Human Immunodeficiency Virus Type-1 (HIV-1)-specific immune responses in healthy adult volunteers that received the multi-gene, polyvalent, DNA prime-protein boost HIV-1 vaccine formulation, DP6−001 in a Phase I clinical trial conducted in healthy adult volunteers of both genders. Robust cross-subtype HIV-1-specific T cell responses were detected in IFNγ ELISPOT assays. Furthermore, we detected high titer serum antibody responses that recognized a wide range of primary HIV-1 Env antigens and also neutralized pseudotyped viruses that express the primary Env antigens from multiple HIV-1 subtypes. These findings demonstrate that the DNA prime-protein boost approach is an effective immunization method to elicit both humoral and cellmediated immune responses in humans, and that a polyvalent Env formulation could generate broad immune responses against HIV-1 viruses with diverse genetic backgrounds.

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Section: Introductionsupporting

confidence: 75%

Section: Methodsmentioning

confidence: 99%

Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime–protein boost HIV-1 vaccine in healthy human volunteers

Wang

Kennedy

West

et al. 2008

Vaccine

Self Cite

124

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“…In other cases, focusing the B-cell response on minor variations in a single epitope has the potential to drive somatic mutations for increased antibody affinity, greater neutralization potency and possibly higher antibody titers [179][180][181]. Few studies have examined polyvalent Env as candidate HIV-1 immunogens and, although outperforming monovalent Env, substantial breadth has not been achieved with early formulations [182][183][184], Notably, these early studies examined a limited number of strains that were not preselected on the basis of their performance as monovalent immunogens. Efforts to improve this strategy might focus on the selection of appropriate strains and ways to enhance the magnitude of antibodyinduction with better adjuvants [185].…”

Section: Novel Immunogen Design Strategiesmentioning

confidence: 99%

Aiming to induce broadly reactive neutralizing antibody responses with HIV-1 vaccine candidates

Haynes¹,

Montefiori²

2006

Expert Review of Vaccines

104

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Neutralizing antibody induction is a key feature of many effective vaccines and is the only immune response that has proven to be capable of completely blocking AIDS virus infection in animal models. Unfortunately, the extensive genetic variability and complex immune-evasion strategies of HIV-1 have thwarted all attempts to date at eliciting an effective neutralizing antibody response with candidate HIV-1 vaccine immunogens. Recent advances in our understanding of how these evasion strategies operate, coupled with growing progress in unravelling the structure and immunobiology of the viral envelope glycoproteins, are contributing to novel immunogen designs to overcome the many barriers to inducing protective antibodies against HIV-1. Keywordsantiretroviral therapy; HIV-1; host cell fusion; immunogen; neutralizing antibody induction Development of a safe, practical and effective HIV-1 vaccine is one of the highest priorities of the global scientific community [1,2]. Although antiretroviral therapy (ART) has dramatically prolonged the lives of HIV-1 infected patients, ART is not yet routinely available in developing countries, and the global rate of spread of HIV-1 continues unabated. If no effective AIDS vaccine is developed by 2010, the number of people infected world-wide with HIV-1 could exceed 60 million [3].In spite of more than 20 years of research, the types of immune responses needed to protect an immunized individual from HIV-1 infection are not known. Its is known that CD8 + cytotoxic T-cell responses can control HIV-1 replication to varying degrees in acute HIV-1 infection (AHI) [4,5], and when induced by immunogens, can control viral set point after simian immunodeficiancy virus (SIV) or simian HIV (SHIV) challenges in non-human primates [4]. Strong proliferative CD4 + T-cell responses to HIV-1 proteins have been demonstrated to correlate well with immune control of HIV-1 viral load [5]. Therefore, it is highly desirable for an HIV-1 vaccine co induce robust CD4 + and CD8 + T-cell responses in order to control virus replication and reduce the likelihood of subsequent transmission [4][5][6][7]. The potential for complete ('sterilizing') immunity from HIV-1 infection may depend on the presence of pre-existing neutralizing antibodies. We know that neutralizing antibodies can prevent the acquisition of AIDS virus infection after intravenous, vaginal, rectal and oral virus challenge in nonhuman primates [8][9][10][11][12]. This level of protection is highly attractive for a vaccine against a virus, such as HIV-1, which integrates genetically and forms latent viral reservoirs soon after infection. However, the diversity of transmitted HIV-1 genetic variants and the relative resistance of the majority of HIV-1 primary isolates to most types of inducible neutralizing antibodies have posed major hurdles to current vaccine efforts. Furthermore, the few rare broadly reactive neutralizing monoclonal antibodies (mAbs) that have been isolated from HIV-1 infected patients represent species of antibodies that...

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“…DNA vaccines are generally effective at stimulating CD8 responses, whilst subunit vaccines are more effective at eliciting antibody responses (Barouch et al, 2000;Earl et al, 2001Earl et al, , 2002Patterson et al, 2004;Robinson, 1999). Combined-modality DNA prime-protein boost vaccination strategies have been evaluated in the past (Cristillo et al, 2006;Letvin et al, 1997;Mooij et al, 2004;Otten et al, 2005;Pal et al, 2005Pal et al, , 2006Robinson et al, 1999). As with single-modality envelope protein-based vaccines (Berman et al, 1990;Bruck et al, 1994;Girard et al, 1991;Hu et al, 1992;Mooij et al, 1998;Verschoor et al, 1999), protection against homologous, non-pathogenic simian-human immunodeficiency virus (SHIV) can be obtained (Letvin et al, 1997;Pal et al, 2006;Robinson et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Immune-response profiles induced by human immunodeficiency virus type 1 vaccine DNA, protein or mixed-modality immunization: increased protection from pathogenic simian–human immunodeficiency virus viraemia with protein/DNA combination

Koopman

Mortier

Hofman

et al. 2008

Journal of General Virology

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Current data suggest that prophylactic human immunodeficiency virus type 1 (HIV) vaccines will be most efficacious if they elicit a combination of adaptive humoral and T-cell responses. Here, we explored the use of different vaccine strategies in heterologous prime–boost regimes and evaluated the breadth and nature of immune responses in rhesus monkeys induced by epidermally delivered plasmid DNA or recombinant HIV proteins formulated in the AS02A adjuvant system. These immunogens were administered alone or as either prime or boost in mixed-modality regimes. DNA immunization alone induced cell-mediated immune (CMI) responses, with a strong bias towards Th1-type cytokines, and no detectable antibodies to the vaccine antigens. Whenever adjuvanted protein was used as a vaccine, either alone or in a regime combined with DNA, high-titre antibody responses to all vaccine antigens were detected in addition to strong Th1- and Th2-type CMI responses. As the vaccine antigens included HIV-1 Env, Nef and Tat, as well as simian immunodeficiency virus (SIV)mac239 Nef, the animals were subsequently exposed to a heterologous, pathogenic simian–human immunodeficiency virus (SHIV)89.6p challenge. Protection against sustained high virus load was observed to some degree in all vaccinated groups. Suppression of virus replication to levels below detection was observed most frequently in the group immunized with protein followed by DNA immunization, and similarly in the group immunized with DNA alone. Interestingly, control of virus replication was associated with increased SIV Nef- and Gag-specific gamma interferon responses observed immediately following challenge.

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Polyvalent DNA prime and envelope protein boost HIV‐1 vaccine elicits humoral and cellular responses and controls plasma viremia in rhesus macaques following rectal challenge with an R5 SHIV isolate

Cited by 53 publications

References 33 publications

Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime–protein boost HIV-1 vaccine in healthy human volunteers

Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime–protein boost HIV-1 vaccine in healthy human volunteers

Aiming to induce broadly reactive neutralizing antibody responses with HIV-1 vaccine candidates

Immune-response profiles induced by human immunodeficiency virus type 1 vaccine DNA, protein or mixed-modality immunization: increased protection from pathogenic simian–human immunodeficiency virus viraemia with protein/DNA combination

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