Immunogenicity of a universal HIV-1 vaccine vectored by DNA, MVA and CHADV-63 in a Phase I/IIA clinical trial

Borthwick, NJ; Ahmed, Tina; Rose, A; Ebrahimsa, U; Black, Antony P.; Hayton, E; Yang, Hongbing; Hancock, Gemma; Campion, Suzanne; Frahm, Nicole; Colloca, Stefano; Nicosia, A.; McMichael, A J; Dorrell, Lucy; Hanke, Tomáš

doi:10.1186/1742-4690-9-s2-p118

Cited by 5 publications

(4 citation statements)

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“…The resulting ChAdV68.GagB vaccine was evaluated for protective efficacy in combinations with plasmid pTH.GagB DNA and modified vaccinia virus Ankara MVA.GagB. This work extends on previously published mouse data [17,20], and parallels rhesus macaque [11,19,21] and ongoing phase I/IIa clinical trial [38] studies exploring similar regimens.…”

Section: Introductionmentioning

confidence: 70%

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T cells induced by recombinant chimpanzee adenovirus alone and in prime‐boost regimens decrease chimeric EcoHIV/NDK challenge virus load

et al. 2012

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The popularity of nonreplicating adenoviruses of chimpanzee origin (ChAdVs) as vectors for subunit vaccines is on the rise. This is mainly for their excellent safety and impressive immunogenicity observed in human studies to date. Here, we recloned the chimpanzee adenovirus sero type 68 (ChAdV-68), also designated SAdV-25 and AdC68, genome and demonstrated its straightforward genetic manipulation facilitated by the use of bacterial artificial chromosome recombineering. To generate the ChAdV68.GagB vaccine, the HIV-1 consensus clade B Gag-derived Tg was inserted into the E1 region. In part confirming previous observations, the ChAdV68.GagB vaccine alone and in heterologous prime-boost regimens with plasmid DNA- and modified vaccinia virus Ankara (MVA)-vectored vaccines induced robust polyfunctional HIV-1-specific CD8+ and CD4+ T-cell responses with a gut-homing phenotype. Importantly, we showed that when a single epitope is expressed as an immunodominant CD8+ T-cell determinant, responses elicited by ChAdV68.GagB alone and in combination lowered surrogate challenge EcoHIV/NDK (where EcoHIV is chimeric ecotropic HIV) virus load in mice both at the peak T-cell frequencies 2 weeks after vaccination and 16 weeks later indicating development of protective effector memory. These results parallel the immunogenicity of similar vaccine regimens in macaques and an ongoing phase I/IIa trial in humans, and support further development of vaccines vectored by ChAdVs.

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Section: Introductionmentioning

confidence: 70%

“…We are currently evaluating in phase I/IIa clinic trial triple regimens of DDDCM and DDDMC using recombinant ChAdV‐63 as the simian adenovirus vector. Therefore here, we also tested triple regimens of DCM and DMC in the mouse EcoHIV/NDK challenge model.…”

Section: Resultsmentioning

confidence: 99%

T cells induced by recombinant chimpanzee adenovirus alone and in prime‐boost regimens decrease chimeric EcoHIV/NDK challenge virus load

et al. 2012

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“…Thus, we showed that a prime with non-replicating recombinant adenovirus of chimpanzee origin followed by a boost with recombinant MVA induced uniquely high frequencies of HIV-1-specific T cells in UK adults [57]. As for the immunogen, HIVA has been superseded by universal pan-clade immunogen HIVconsv, which is based on the 14 most conserved regions of the HIV-1 proteome to tackle HIV-1 diversity and escape [57-59]. Furthermore, we plan to include component(s) inducing broadly neutralizing antibodies into the final vaccine regimen when these become available.…”

Section: Discussionmentioning

confidence: 99%

A Phase I Randomized Clinical Trial of Candidate Human Immunodeficiency Virus type 1 Vaccine MVA.HIVA Administered to Gambian Infants

Afolabi

Ndure²,

Drammeh³

et al. 2013

PLoS ONE

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BackgroundA vaccine to decrease transmission of human immunodeficiency virus type 1 (HIV-1) during breast-feeding would complement efforts to eliminate infant HIV-1 infection by antiretroviral therapy. Relative to adults, infants have distinct immune development, potentially high-risk of transmission when exposed to HIV-1 and rapid progression to AIDS when infected. To date, there have been only three published HIV-1 vaccine trials in infants.Trial DesignWe conducted a randomized phase I clinical trial PedVacc 001 assessing the feasibility, safety and immunogenicity of a single dose of candidate vaccine MVA.HIVA administered intramuscularly to 20-week-old infants born to HIV-1-negative mothers in The Gambia.MethodsInfants were followed to 9 months of age with assessment of safety, immunogenicity and interference with Expanded Program on Immunization (EPI) vaccines. The trial is the first stage of developing more complex prime-boost vaccination strategies against breast milk transmission of HIV-1.ResultsFrom March to October 2010, 48 infants (24 vaccine and 24 no-treatment) were enrolled with 100% retention. The MVA.HIVA vaccine was safe with no difference in adverse events between vaccinees and untreated infants. Two vaccine recipients (9%) and no controls had positive ex vivo interferon-γ ELISPOT assay responses. Antibody levels elicited to the EPI vaccines, which included diphtheria, tetanus, whole-cell pertussis, hepatitis B virus, Haemophilus influenzae type b and oral poliovirus, reached protective levels for the vast majority and were similar between the two arms.ConclusionsA single low-dose of MVA.HIVA administered to 20-week-old infants in The Gambia was found to be safe and without interference with the induction of protective antibody levels by EPI vaccines, but did not alone induce sufficient HIV-1-specific responses. These data support the use of MVA carrying other transgenes as a boosting vector within more complex prime-boost vaccine strategies against transmission of HIV-1 and/or other infections in this age group.Trial RegistrationClinicalTrials.gov NCT00982579 The Pan African Clinical Trials Registry PACTR2008120000904116

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“…For Ad26, clinical development will be necessary to further evaluate immunogenicity since replication of this Ad serotype is restricted in simian cells. Finally, because nonreplicating chimp Ads have shown promise in human trials [78, 79], new simian viruses are being identified [35] and developed as RC vectors (D. Barouch, personal communication).…”

Section: Dna Virus Vectorsmentioning

confidence: 99%

Development of replication-competent viral vectors for HIV vaccine delivery

Parks

Picker

King

2013

Current Opinion in HIV and AIDS

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Purpose of review Briefly describe some of the replication-competent (RC) vectors being investigated for development of candidate HIV vaccines focusing primarily on technologies that have advanced to testing in macaques or have entered clinical trials. Recent findings RC viral vectors have advanced to the stage were decisions can be made regarding future development of HIV vaccines. The viruses being used as RC vector platforms vary considerably, and their unique attributes make it possible to test multiple vaccine design concepts and also mimic various aspects of an HIV infection. RC viral vectors encoding SIV or HIV proteins can be used to safely immunize macaques, and in some cases, there is evidence of significant vaccine efficacy in challenge protection studies. Several live HIV vaccine vectors are in clinical trials to evaluate immunogenicity, safety, the effect of mucosal delivery, and potential effects of pre-existing immunity. Summary A variety of DNA and RNA viruses are being used to develop RC viral vectors for HIV vaccine delivery. Multiple viral vector platforms have proven to be safe and immunogenic with evidence of efficacy in macaques. Some of the more advanced HIV vaccine prototypes based on vesicular stomatitis virus, vaccinia virus, measles virus, and Sendai virus are in clinical trials.

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Immunogenicity of a universal HIV-1 vaccine vectored by DNA, MVA and CHADV-63 in a Phase I/IIA clinical trial

Cited by 5 publications

References 0 publications

T cells induced by recombinant chimpanzee adenovirus alone and in prime‐boost regimens decrease chimeric EcoHIV/NDK challenge virus load

T cells induced by recombinant chimpanzee adenovirus alone and in prime‐boost regimens decrease chimeric EcoHIV/NDK challenge virus load

A Phase I Randomized Clinical Trial of Candidate Human Immunodeficiency Virus type 1 Vaccine MVA.HIVA Administered to Gambian Infants

Development of replication-competent viral vectors for HIV vaccine delivery

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