Dataset Information

Long-term mucosal T cell activation and homing phenotypes in recipients of an Ad5-vectored HIV vaccine.

ABSTRACT:

Background

Vaccine-induced mucosal immune responses may be critical for protection against HIV infection, but may also result in short or long-term changes that enhance susceptibility to infection in some individuals, such as those with baseline seroreactivity to vaccine vector antigens. We examined cellular immune responses in blood and gut mucosal tissue roughly two years following vaccination with placebo or the Step study vaccine MRKAd5/HIV-1.

Methods

Participants vaccinated with either placebo or MRKAd5/HIV-1 during participation in HVTN 071, and HVTN 502/Merck 023 underwent phlebotomy and colonic mucosal biopsies via flexible sigmoidoscopy at two timepoints roughly six months apart. After isolation of mononuclear cells, we compared cellular phenotypes and intracellular cytokine responses in vaccine and placebo recipients with and without baseline serological reactivity to Ad5.

Results

Surface expression of activation and gut-homing markers were elevated on CD4 + and CD8 + gut mucosal mononuclear cells (GMMC) in comparison with PBMC (p < 0.01), but were not significantly affected by baseline Ad5 serostatus or receipt of MRKAd5/HIV-1. ICS responses to stimulation with vaccine antigens were of low frequency and magnitude. Ad5 vector responses were seen in vaccinees and baseline seropositive individuals. CD4 + responses to vector antigens were more common in GMMC than PBMC (p < 0.01) and CD8 + responses to HIV gag insert antigens were more frequent in Ad5 seropositive than Ad5 seronegative individuals (p = 0.03).

Conclusion

Vaccination with the Ad5 vectored candidate HIV vaccine MRKAd5/HIV-1 does not lead to long-term changes in the activation state of mucosal CD4 + or CD8 + T lymphocytes regardless of baseline Ad5 serostatus. The findings of this study do not reveal a basis for enhanced susceptibility to HIV infection two years post vaccination.

SUBMITTER: Curlin ME

PROVIDER: S-EPMC8357155 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Induction of protective anti-human immunodeficiency virus (HIV) immune responses is the goal of an HIV vaccine. However, this may cause a reactive result in routine HIV testing in the absence of HIV infection.To evaluate the frequency of vaccine-induced seropositivity/reactivity (VISP) in HIV vaccine trial participants.Three common US Food and Drug Administration-approved enzyme immunoassay (EIA) HIV antibody kits were used to determine VISP, and a routine diagnostic HIV algorithm was used to evaluate VISP frequency in healthy, HIV-seronegative adults who completed phase 1 (n = 25) and phase 2a (n = 2) vaccine trials conducted from 2000-2010 in the United States, South America, Thailand, and Africa.Vaccine-induced seropositivity/reactivity, defined as reactive on 1 or more EIA tests and either Western blot-negative or Western blot-indeterminate/atypical positive (profile consistent with vaccine product) and HIV-1-negative by nucleic acid testing.Among 2176 participants free of HIV infection who received a vaccine product, 908 (41.7%; 95% confidence interval [CI], 39.6%-43.8%) had VISP, but the occurrence of VISP varied substantially across different HIV vaccine product types: 399 of 460 (86.7%; 95% CI, 83.3%-89.7%) adenovirus 5 product recipients, 295 of 552 (53.4%; 95% CI, 49.2%-57.7%) recipients of poxvirus alone or as a boost, and 35 of 555 (6.3%; 95% CI, 4.4%-8.7%) of DNA-alone product recipients developed VISP. Overall, the highest proportion of VISP (891/2176 tested [40.9%]) occurred with the HIV 1/2 (rDNA) EIA kit compared with the rLAV EIA (150/700 tested [21.4%]), HIV-1 Plus O Microelisa System (193/1309 tested [14.7%]), and HIV 1/2 Peptide and HIV 1/2 Plus O (189/2150 tested [8.8%]) kits. Only 17 of the 908 participants (1.9%) with VISP tested nonreactive using the HIV 1/2 (rDNA) kit. All recipients of a glycoprotein 140 vaccine (n = 70) had VISP, with 94.3% testing reactive with all 3 EIA kits tested. Among 901 participants with VISP and a Western blot result, 92 (10.2%) had a positive Western blot result (displaying an atypical pattern consistent with vaccine product), and 592 (65.7%) had an indeterminate result. Only 8 participants with VISP received a vaccine not containing an envelope insert.The induction of VISP in HIV vaccine recipients is common, especially with vaccines containing both the HIV-1 envelope and group-specific core antigen gene proteins. Development and detection of VISP appear to be associated with the immunogenicity of the vaccine and the EIA assay used.