Development of prophylactic vaccines against HIV-1

Schiffner, Torben; Sattentau, Quentin J.; Dorrell, Lucy

doi:10.1186/1742-4690-10-72

Cited by 65 publications

(60 citation statements)

References 183 publications

(191 reference statements)

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“…During this time, efforts to identify correlates of immune protection have yielded a number of critical observations. From a humoral perspective, the characterization of broadly neutralizing antibodies and the plasma cells that secrete these antibodies suggests that specific routes of B cell immune maturation are key to eliciting protective immunity (29)(30)(31)(32). From a T cell perspective, the presentation of viral peptide ligands by particular HLA molecules, in conjunction with specific T cell receptor usage, correlates with protection from both infection and disease progression (33).…”

Section: Discussionmentioning

confidence: 99%

Direct Interrogation of Viral Peptides Presented by the Class I HLA of HIV-Infected T Cells

Yaciuk

Skaley

Bardet

et al. 2014

J Virol

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Section: Discussionmentioning

confidence: 99%

Direct Interrogation of Viral Peptides Presented by the Class I HLA of HIV-Infected T Cells

Yaciuk

Skaley

Bardet

et al. 2014

J Virol

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“…Besides the choice of antigen as the core component of any vaccine, the mode of delivery, the immunization regimen, route, and dose, and the exploitation of immunemodulating factors, either added in trans as adjuvants or representing intrinsic properties of, e.g., vector systems, may also affect vaccine efficacy. Current approaches are mainly focused on the induction of antibody responses, as they are considered to prevent infection, while CD8 ϩ cytotoxic T lymphocyte (CTL) responses are generally thought to modify disease progression by reducing viral loads (1). However, recent studies of rhesus macaques immunized with a novel cytomegalovirus (CMV) vector indicate the potentially protective role of CD8 ϩ T cells, especially those with an effector memory phenotype (2)(3)(4).…”

mentioning

confidence: 99%

Potential To Streamline Heterologous DNA Prime and NYVAC/Protein Boost HIV Vaccine Regimens in Rhesus Macaques by Employing Improved Antigens

Asbach

Kliche

Köstler

et al. 2016

J Virol

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In a follow-up to the modest efficacy observed in the RV144 trial, researchers in the HIV vaccine field seek to substantiate and extend the results by evaluating other poxvirus vectors and combinations with DNA and protein vaccines. Earlier clinical trials (EuroVacc trials 01 to 03) evaluated the immunogenicity of HIV-1 clade C GagPolNef and gp120 antigens delivered via the poxviral vector NYVAC. These showed that a vaccination regimen including DNA-C priming prior to a NYVAC-C boost considerably enhanced vaccine-elicited immune responses compared to those with NYVAC-C alone. Moreover, responses were improved by using three as opposed to two DNA-C primes. In the present study, we assessed in nonhuman primates whether such vaccination regimens can be streamlined further by using fewer and accelerated immunizations and employing a novel generation of improved DNA-C and NYVAC-C vaccine candidates designed for higher expression levels and more balanced immune responses. Three different DNA-C prime/NYVAC-C؉ protein boost vaccination regimens were tested in rhesus macaques. All regimens elicited vigorous and well-balanced CD8 ؉ and CD4 ؉ T cell responses that were broad and polyfunctional. Very high IgG binding titers, substantial antibody-dependent cellular cytotoxicity (ADCC), and modest antibody-dependent cell-mediated virus inhibition (ADCVI), but very low neutralization activity, were measured after the final immunizations. Overall, immune responses elicited in all three groups were very similar and of greater magnitude, breadth, and quality than those of earlier EuroVacc vaccines. In conclusion, these findings indicate that vaccination schemes can be simplified by using improved antigens and regimens. This may offer a more practical and affordable means to elicit potentially protective immune responses upon vaccination, especially in resource-constrained settings. IMPORTANCEWithin the EuroVacc clinical trials, we previously assessed the immunogenicity of HIV clade C antigens delivered in a DNA prime/NYVAC boost regimen. The trials showed that the DNA prime crucially improved the responses, and three DNA primes with a NYVAC boost appeared to be optimal. Nevertheless, T cell responses were primarily directed toward Env, and humoral responses were modest. The aim of this study was to assess improved antigens for the capacity to elicit more potent and balanced responses in rhesus macaques, even with various simpler immunization regimens. Our results showed that the novel antigens in fact elicited larger numbers of T cells with a polyfunctional profile and a good Env-GagPolNef balance, as well as high-titer and Fc-functional antibody responses. Finally, comparison of the different schedules indicates that a simpler regimen of only two DNA primes and one NYVAC boost in combination with protein may be very efficient, thus showing that the novel antigens allow for easier immunization protocols.

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“…Strikingly, if there is a longer time delay in the production of effector function (small cq), increasing the abundance of memory CTL even by four orders of magnitude does not lead to a significant reduction of the peak virus load and thus of clinical symptoms (Figure 3). This might contribute to the finding that CTL-based vaccines have not been very effective in a variety of different viral infections, a prominent example being HIV [29]. …”

Section: Memory Ctl and Protection Against Re-infectionmentioning

confidence: 99%

Modeling T cell responses to antigenic challenge

Wodarz

2014

J Pharmacokinet Pharmacodyn

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T cell responses are a crucial part of the adaptive immune system in the fight against infections. This article discusses the use of mathematical models for understanding the dynamics of cytotoxic T lymphocyte (CTL) responses against viral infections. Complementing experimental research, mathematical models have been very useful for exploring new hypotheses, interpreting experimental data, and for defining what needs to be measured to improve understanding. This review will start with minimally parameterized models of CTL responses, which have generated some valuable insights into basic dynamics and correlates of control. Subsequently, more biological complexity is incorporated into this modeling framework, examining different mechanisms of CTL expansion, different effector activities, and the influence of T cell help. Models and results are discussed in the context of data from specific infections.

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Development of prophylactic vaccines against HIV-1

Cited by 65 publications

References 183 publications

Direct Interrogation of Viral Peptides Presented by the Class I HLA of HIV-Infected T Cells

Direct Interrogation of Viral Peptides Presented by the Class I HLA of HIV-Infected T Cells

Potential To Streamline Heterologous DNA Prime and NYVAC/Protein Boost HIV Vaccine Regimens in Rhesus Macaques by Employing Improved Antigens

Modeling T cell responses to antigenic challenge

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