2016
DOI: 10.1371/journal.pone.0152952
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Early CD4+ T Cell Responses Are Associated with Subsequent CD8+ T Cell Responses to an rAd5-Based Prophylactic Prime-Boost HIV Vaccine Strategy

Abstract: IntroductionInitial evaluation of a candidate vaccine against HIV includes an assessment of the vaccine’s ability to generate immune responses. However, the dynamics of vaccine-induced immune responses are unclear. We hypothesized that the IFN-γ producing cytotoxic CD8+ (CD8+ IFN-γ+) T cell responses could be predicted by early IL-2 producing CD4+ (CD4+ IL-2+) helper T cell responses, and we evaluated this hypothesis using data from a phase I/II prophylactic HIV vaccine trial. The objective was to assess the d… Show more

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Cited by 4 publications
(5 citation statements)
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“…Consistent with previous reports, the vaccinations were generally well tolerated, 21 , 22 , 43 , 44 without differences between groups ( Supplementary Figure S2 , Supplementary Table S4 ). Distributing antigen to multiple sites, up to four, did not affect tolerability or safety and thus the non-standard delivery strategies of this regimen had a similar safety profile as standard vaccination.…”
Section: Resultssupporting
confidence: 90%
“…Consistent with previous reports, the vaccinations were generally well tolerated, 21 , 22 , 43 , 44 without differences between groups ( Supplementary Figure S2 , Supplementary Table S4 ). Distributing antigen to multiple sites, up to four, did not affect tolerability or safety and thus the non-standard delivery strategies of this regimen had a similar safety profile as standard vaccination.…”
Section: Resultssupporting
confidence: 90%
“…Members of this species cause a significant proportion of acute respiratory tract infections in children [179,180]. Despite widespread pre-existing immunity, HAdV-C5 vectors are currently being used as vaccine platforms in many countries, principally against HIV [181,182], malaria [183,184,185], Ebola virus [186,187,188,189,190], influenza virus [191], tuberculosis [192,193], or in pre-clinical studies that are targeting Zika virus [194,195], Clostridium botulinum [196], type O foot-and-mouth disease virus [197], Middle East respiratory syndrome coronavirus [198,199], rabies virus [200,201], or Dengue virus [202]. In mice and NHPs, HAdV-C2 delivered antigens protected against Ebola virus [203].…”
Section: S and 1960s: Hadvs Etiology And Pathogenicitymentioning
confidence: 99%
“…The frequency and magnitude of Gag ELISPOT responses in the S L A and S H A groups combined were equivalent to those of Ad35-GRIN given twice intramuscularly, indicating that SeV-Gag given intranasally provides as strong a prime as an Ad vector given intramuscularly [31]. A so-called hidden prime has been postulated previously in studies of DNA vaccines followed by Ad vector boosts [43, 44], in which plasmid DNA vaccines with or without electroporation and/or molecular adjuvants such as interleukin 12 or interleukin 15 elicit very modest T-cell and antibody responses in humans, but prime for anamnestic responses when Ad vectors are given as a boost [8, 4549]. One dose of SeV-Gag appears to be equivalent to 3 doses of DNA vaccine (up to 8 mg) in terms of priming responses and is perhaps more effective at priming than a highly attenuated VSV-Gag delivered intramuscularly [6, 50, 51].…”
Section: Discussionmentioning
confidence: 84%
“…One dose of SeV-Gag appears to be equivalent to 3 doses of DNA vaccine (up to 8 mg) in terms of priming responses and is perhaps more effective at priming than a highly attenuated VSV-Gag delivered intramuscularly [6, 50, 51]. The ICS studies demonstrated that SeV-Gag stimulated CD4 + T cells, which may have provided help for the development of CD8 + T cells [44]. It was not possible in this study to determine how SeV-Gag provides this potent T-cell priming; its ability to infect mucosal cells after intranasal delivery may be important.…”
Section: Discussionmentioning
confidence: 99%