Design and construction of an experimental HIV-1 vaccine for a year-2000 clinical trial in Kenya.

Hanke, Tomáš; McMichael, Andrew J.

doi:10.1038/79626

Cited by 182 publications

(171 citation statements)

References 46 publications

Supporting

Mentioning

167

Contrasting

Unclassified

Order By: Relevance

“…These doses and timing mimicked those of the HIVA vaccines used in clinical trial IAVI 006 (manuscript in preparation). To facilitate detailed analyses of vaccineinduced CD8 + T cell responses in pre-clinical NHP studies, two immunodominant SIV-derived Mamu-A*01-restricted epitopes, CTPYDINQM (Gag) and STPESANL (Tat), were incorporated into the HIVA and RENTA immunogens, respectively [25,28]. Employing the corresponding peptides and overlapping peptide pools across the two immunogens, vaccine-elicited T cell responses recognizing multiple epitopes were readily detected after priming with the DNA vaccines ( Fig.…”

Section: Early Vaccine-induced T Cell Responsesmentioning

confidence: 99%

“…The preparation of the pTHr.HIVA, pTHr.RENTA, MVA.HIVA and MVA.RENTA vaccines was described previously [25,28]. The plasmid DNA and rMVA were prepared in compliance with Good Manufacturing Practice by Cobra Biomanufacturing (UK) and IDT (Germany), respectively.…”

Section: The Vaccinesmentioning

confidence: 99%

“…To assess the protective role of vaccine-induced T cells in the absence of any HIV-1-binding antibody, neutralizing or not, we constructed a DNA primemodified vaccinia virus Ankara (MVA) boost candidate HIV-1 vaccine expressing a common immunogen HIVA derived from consensus HIV-1 clade A Gag p24/p17 sequences and a string of CD8 + T cell epitopes [25]. Through gradual pre-clinical and clinical protocol improvements, we were able to demonstrate priming of HIV-1-specific T cell responses in 8/8 healthy and boost pre-existing HIV-1-specific responses in 16/16 HIV-1-infected vaccine recipients [26,27].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Induction of long‐lasting multi‐specific CD8⁺T cells by a four‐component DNA‐MVA/HIVA‐RENTA candidate HIV‐1 vaccine in rhesus macaques

Nkolola

Gléria

et al. 2006

Eur J Immunol

View full text Add to dashboard Cite

As a part of a long‐term effort to develop vaccine against HIV‐1 clade A inducing protective T cell responses in humans, we run mutually complementing studies in humans and non‐human primates (NHP) with the aim to maximize vaccine immunogenicity. The candidate vaccine under development has four components, pTHr.HIVA and pTH.RENTA DNA, and modified vaccinia virus Ankara (MVA).HIVA and MVA.RENTA, delivered in a heterologous DNA prime‐MVA boost regimen. While the HIVA (Gag/epitopes) components have been tested in NHP and over 300 human subjects, we plan to test in humans the RENTA (reverse transcriptase, gp41, Nef, Tat) vaccines designed to broaden HIVA‐induced responses in year 2007. Here, we investigated the four‐component vaccine long‐term immunogenicity in Mamu‐A*01‐positive rhesus macaques and demonstrated that the vaccine‐induced T cells were multi‐specific, multi‐functional, readily proliferated to recall peptides and were circulating in the peripheral blood of vaccine recipients over 1 year after vaccine administration. The consensus clade A‐elicited T cells recognized 50% of tested epitope variants from other HIV‐1 clades. Thus, the DNA‐MVA/HIVA‐RENTA vaccine induced memory T cells of desirable characteristics and similarities to those induced in humans by HIVA vaccines alone; however, single‐clade vaccines may not elicit sufficiently cross‐reactive responses.

show abstract

Section: Early Vaccine-induced T Cell Responsesmentioning

confidence: 99%

Section: The Vaccinesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Induction of long‐lasting multi‐specific CD8⁺T cells by a four‐component DNA‐MVA/HIVA‐RENTA candidate HIV‐1 vaccine in rhesus macaques

Nkolola

Gléria

et al. 2006

Eur J Immunol

View full text Add to dashboard Cite

show abstract

“…To overcome the low frequency of naive cells, we utilised mouse strain F5 transgenic for TCR recognizing epitope ASNENMDAM and vaccine MVA.HIVA-NP [36], a derivative of the current clinical trial vaccine MVA.HIVA [37]. The recognized epitope is derived from the influenza virus nucleoprotein (NP) and is presented by MHC class I molecule H-2D b .…”

Section: Introductionmentioning

confidence: 99%

“…Two complementary DNA oligonucleotides coding for the influenza virus NP H-2D b -restricted epitope ASNENMDAM were inserted into the unique EcoRI site of plasmid pTH.HIVA [37]. From the resulting pTH.HIVA-NP plasmid, the HIVA-NP open reading frame was excised using the HindIII and XhoI restriction endonucleases, the ends were blunted by the Klenow fragment of DNA polymerase and inserted in to the unique SmaI site of plasmid pSC11 [45], and the resulting pSC11.HIVA-NP was used to construct MVA.HI-VA-NP as described previously [36,37]. MVA.HIVA-NP was subjected to five rounds of plaque purification, expanded, purified on a 36% sucrose gradient and titered.…”

mentioning

confidence: 99%

Altered primary CD8⁺ T cell response to a modified virus Ankara(MVA)‐vectored vaccine in the absence of CD4⁺ T cell help

Estcourt¹,

McMichael²,

Hanke³

2005

Eur J Immunol

View full text Add to dashboard Cite

T cell receptor-transgenic F5 mice were used to assess primary CD8 + T cell responses to a modified virus Ankara (MVA)-vectored vaccine in the absence of CD4 + T cell help. Naive, CD8-enriched, CFSE-labelled F5 cells were transferred into normal or CD4 + celldepleted mice and the mice were vaccinated with MVA.HIVA-NP. At different time points during the primary response, F5 cells were re-isolated and analysed on divisional basis for a number of parameters. We demonstrated that the primary CD8 + T cell response in the absence of CD4 + T cell help differed from that in normal CD4 + cellundepleted mice. While in the absence of CD4 + T cell help, the initial migratory progress from the local response to a systemic one was not grossly affected, the proportion of dying F5 cells during the expansion phase was markedly increased and resulted in an overall smaller expansion and significantly decreased frequency of CD8 + T cell memory after contraction. T cells primed without help displayed accelerated proliferation and activation, while expression of interferon-c remained similar. These phenomena were observed in the lymph nodes draining the MVA.HIVA-NP immunization site and were similar, but delayed by 2-3 days in spleen and non-draining lymph nodes. IntroductionCD8 + T cells form an important part of the immune defence against many intracellular pathogens including viruses. Historically, CD8 + T cell responses against viral infections were considered to be independent from 'help' provided by CD4 + T cells. This was explained by direct activation of antigen-presenting DC by viruses, which provided ligands for Toll-like receptors and proinflammatory signals [1][2][3]. Recently, this view was revised by studies of non-inflammatory antigens which suggested that while primary CD8 + T cell response was CD4 + T cell-independent, secondary CD8 + T cell response, i.e. development of functional memory, was dependent on CD4 + T cell help during priming. These data led to the formulation of a programming model [4][5][6]. In contrast, another set of recent studies pointed towards an environmental model and proposed that CD4 + T cells were required to enhance survival of fully functional memory CD8 + T cells rather than imparting essential programming during the primary response [7,8]. The differences in these conclusions may be explained by the use of different antigens and immunization protocols, which might lead to differential activation of DC. Collectively, these and other experiments [9][10][11][12][13] not required for triggering the CD8 + T cell program of multiple cell divisions, effector function maturation and cell number contraction, but was needed for differentiation into functional CD8 + T cell memory and/or its maintenance.To date, most studies investigated secondary responses to make conclusions about the dependence of the CD8 + T cell responses on CD4 help. This is partially because induction of a good memory is the ultimate aim of a successful vaccination, but also because primary CD8 + T cell responses to non-inf...

show abstract

Cytotoxic T lymphocytes recognize structurally diverse, clade-specific and cross-reactive peptides in human immunodeficiency virus type-1 gag through HLA-B53

et al. 2001

View full text Add to dashboard Cite

Human immunodeficiency virus type‐1 (HIV‐1) cytotoxic T lymphocyte (CTL) epitopes have largely been defined in Caucasian populations infected with clade B virus. Identification of potentially protective CTL epitopes in non‐B clade‐infected African subjects is important for vaccine development. In a study of CTL responses in clade A‐infected Gambians, using cytotoxicity, interferon‐γ (IFN‐γ) enzyme‐linked immunospot (ELISpot) and HLA‐B53‐peptide tetramer assays, we identified three HLA‐B53‐restricted epitopes in HIV‐1 gag p24. CTL specific for an epitope in a highly immunogenic region of the p24 protein showed no cross‐reactivity to other HIV‐1 clades. Two of the epitopes would not have been predicted from the peptide‐binding motif due to the absence of a proline anchor at position 2. Structural analysis of HLA‐B53 and its relative, HLA B35, enabled us to re‐define the peptide‐binding motif to include other P2 anchors. These results demonstrate the value of combined immunological and structural analyses in defining novel CTL epitopes and have implications for HIV‐1 vaccine design.

show abstract

Design and construction of an experimental HIV-1 vaccine for a year-2000 clinical trial in Kenya.

Cited by 182 publications

References 46 publications

Induction of long‐lasting multi‐specific CD8⁺T cells by a four‐component DNA‐MVA/HIVA‐RENTA candidate HIV‐1 vaccine in rhesus macaques

Induction of long‐lasting multi‐specific CD8⁺T cells by a four‐component DNA‐MVA/HIVA‐RENTA candidate HIV‐1 vaccine in rhesus macaques

Altered primary CD8⁺ T cell response to a modified virus Ankara(MVA)‐vectored vaccine in the absence of CD4⁺ T cell help

Cytotoxic T lymphocytes recognize structurally diverse, clade-specific and cross-reactive peptides in human immunodeficiency virus type-1 gag through HLA-B53

Contact Info

Product

Resources

About

Design and construction of an experimental HIV-1 vaccine for a year-2000 clinical trial in Kenya.

Cited by 182 publications

References 46 publications

Induction of long‐lasting multi‐specific CD8+ T cells by a four‐component DNA‐MVA/HIVA‐RENTA candidate HIV‐1 vaccine in rhesus macaques

Induction of long‐lasting multi‐specific CD8+ T cells by a four‐component DNA‐MVA/HIVA‐RENTA candidate HIV‐1 vaccine in rhesus macaques

Altered primary CD8+ T cell response to a modified virus Ankara(MVA)‐vectored vaccine in the absence of CD4+ T cell help

Cytotoxic T lymphocytes recognize structurally diverse, clade-specific and cross-reactive peptides in human immunodeficiency virus type-1 gag through HLA-B53

Contact Info

Product

Resources

About

Induction of long‐lasting multi‐specific CD8⁺T cells by a four‐component DNA‐MVA/HIVA‐RENTA candidate HIV‐1 vaccine in rhesus macaques

Induction of long‐lasting multi‐specific CD8⁺T cells by a four‐component DNA‐MVA/HIVA‐RENTA candidate HIV‐1 vaccine in rhesus macaques

Altered primary CD8⁺ T cell response to a modified virus Ankara(MVA)‐vectored vaccine in the absence of CD4⁺ T cell help