A Phase 1 Randomized Double Blinded Placebo Controlled, Dose Ranging Trial, of a Gorilla Adenovirus Vectored Networked Epitopes Vaccine (GRAdHIVNE1 Vaccine), Administered to Healthy Adults Living without HIV and Living with HIV, in Southern Africa
This is a Phase 1 trial for the GRAdHIVNE1 vaccine, designed to evaluate safety, tolerability, and immunogenicity in healthy individuals (PLWoH) including healthy People Living with HIV (PLWH). This study builds on insights from prior T-cell vaccine trials and pre-clinical non-human primate studies, which demonstrated that robust CD8+ T cell responses, are crucial for viral control but require broad, polyfunctional responses that can also effectively counteract HIV's diversity and immune evasion strategies. Inclusion of PLWoH and PLWH in this study is important for safety, tolerability and immunogenicity data that can inform further development of the vaccine for prevention and therapeutic use. Prior clinical trials, using adenovirus vectors and exploring different vaccine approaches, demonstrated safety and potential immunogenic benefits in PLWH, despite not achieving sustained viral suppression post-treatment interruption Understanding these dynamics is key to evaluating the full therapeutic potential of vaccine induced immune responses in controlling HIV as well as inform the potential of the vaccine in aborting the establishment of a disseminated infection in the setting of prevention.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
120
This is a dose ranging study that will allow for simultaneous enrollment of participants in both low and high dose groups.
This is a dose ranging study that will allow for simultaneous enrollment of participants in both low and high dose groups.
AHRI
Mtubatuba, KwaZulu-Natal, South Africa
RECRUITINGDTHF
Cape Town, Western Cape, South Africa
RECRUITINGMutala
Harare, Harare, Zimbabwe
RECRUITINGAssess safety and tolerability of GRAdHIVNE1 vaccine
1\. Proportion of participants with each type of reactogenicity event classified by severity of the events from initial administration through 7 days following completion of each dose of the investigational product.
Time frame: 7 Day
Assessment of unsolicited adverse events (AEs)
Proportion of participants reporting unsolicited adverse events (AEs), including safety laboratory (biochemical, hematological) parameters, classified by severity and causality, from initial administration through 28 days following completion of each dose of the investigational product.
Time frame: 28 day
Assessment of SAEs
Proportion of participants reporting serious adverse events (SAEs) throughout the study period, classified by causality.
Time frame: 19 months
To evaluate cellular immune responses elicited by GRAdHIVNE1 vaccine.
1\. Response rate and magnitude of the vaccine induced HIV specific T cell response at peak immunogenicity as measured by intracellular cytokine staining assay or IFNγ ELISpot assay after each dose.
Time frame: 19 Months
To evaluate cellular immune responses elicited by GRAdHIVNE1 vaccine.
To assess antigen specific proliferative memory T cell responses induced by vaccination.
Time frame: 19 months
To evaluate cellular immune responses elicited by GRAdHIVNE1 vaccine.
To identify immunogenic epitopes within the vaccine immunogen and define the HLA restriction.
Time frame: 19 months
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To evaluate cellular immune responses elicited by GRAdHIVNE1 vaccine.
To define the functional characteristics of antigen specific T cells by assessing proliferation, cytotoxicity, tetramer analysis and TCR sequences.
Time frame: 19 months
To evaluate cellular immune responses elicited by GRAdHIVNE1 vaccine.
To evaluate vaccine induced innate immune responses.
Time frame: 19 months
To evaluate cellular immune responses elicited by GRAdHIVNE1 vaccine.
To characterize vaccine induced de novo T-cell responses compared to pre-existing responses in PLWH (Part B).
Time frame: 19 months
To evaluate cellular immune responses elicited by GRAdHIVNE1 vaccine.
To conduct analyses to further understand HIV and vaccine immunology
Time frame: 19 months