HVTN Clinical Research Agenda Specific Aims

The HVTN has had a request to post, in a transparent fashion, the scope of work that it plans to conduct in the upcoming competition.

The Section C of the HVTN LOC grant requested a detailed discussion (30 pages) of the scientific programs the HVTN planned to conduct in the upcoming grant period. The specific aims of this section are provided below. The intent of this posting is to provide, in a transparent way, for new and recompeting clinical trial sites an overview of the proposed scientific program of the HVTN. The document is specifically designed to accommodate the request from investigators interested in submitting CTU/CRS applications in the vaccine arena.  

This information will be removed post the submission date of the CTU application.

The HVTN Executive Management Team: Larry Corey, Glenda Gray, Dan Barouch, Georgia Tomaras, Susan Buchbinder, Scott Hammer, Jim Kublin, Troy Martin, Julie McElrath, Peter Gilbert

SAC1. To design and execute phase I clinical trials of candidate HIV vaccines.

1a. To execute fast-track experimental medicine studies that assess in a rapidly iterative fashion whether novel trimer, germline-binding or epitope designed vaccines elicit tier 2 neutralizing antibodies to HIV-1 or engage germlines associated with broadly neutralizing antibodies that can then be enhanced through sequential immunization. To develop the laboratory and analytical platforms to determine safety, relative immunogenicity, novelty, and potential to move these candidate immunogens into further clinical development.

1b. To execute novel non-neutralizing vaccine candidates/regimens that are designed to enhance T cells and non-neutralizing antibodies in their magnitude, breadth and function over the regimens utilized in HVTN 702 & 705. 

1c. To conduct phase 2 trials to advance into efficacy testing of selected vaccines, vaccine combinations, adjuvants and delivery systems by establishing consensus go/no-go immune and safety profiles and provide feedback to developers of these results.

SAC2. To design and conduct test-of-concept phase 2b as well as phase 3 licensure studies to determine whether candidate vaccines can significantly reduce acquisition of HIV-1 and/or limit the severity and early events of acquired HIV infection in a wide variety of at-risk populations throughout the world. To establish a robust integrated laboratory, statistical, computational and clinical platform to define, evaluate and analyze correlates of risk and immune protection in efficacy trials, including assessments of virus and host genetic variability between placebo and vaccine recipients; to correlate genotypic pressure with phenotypic immune responses and host factors in individuals as well as groups of vaccine recipients.

SAC3. To develop with the HPTN a clinical trial, laboratory, and correlates program to evaluate passive immunization of single, multiple, or multi-specific broadly neutralizing monoclonal antibodies (mAbs) to reduce HIV acquisition in adults and to explore neutralizing antibody titer as a surrogate marker of protection.

3a. Completion and analysis of the phase 2b AMP studies (Years 1-2)

3b. Evaluation and down-selection of mAb cocktails and multi-specific mAbs (Years 1-3)

3c. Assessment of optimal mAb cocktails or multi-specific mAbs for high-level efficacy for prevention of HIV acquisition in humans from multiple risk groups and geographic regions (Years 3-7).

SAC4. To investigate vaccination in HIV-exposed and unexposed infants to induce bnAbs.

4a. To investigate vaccination in HIV-exposed and unexposed infants to induce broadly neutralizing antibodies using strategies such as B-cell lineage, germline-targeting, epitope-specific or SOSIP trimer immunogens.

4b. To evaluate the safety, immunogenicity and response durability of candidate vaccines in infants and other pediatric populations once efficacy in adults has been established.

4c. To explore the role of passive immunization of broadly neutralizing antibodies in protecting infants against breastmilk transmission of HIV-1 in collaboration with other networks that work with children and adolescents.

4d. To evaluate pregnancy-related outcomes of women who become pregnant in HIV or TB vaccine trials, including the follow-up of pregnant women and the evaluation of infant safety with the support of other networks working with women and infants.

SAC5. In partnership with ACTG and IMPAACT Network to form an integrated clinical trials program for TB that includes immunological, microbiological and diagnostic technologies to enhance the TB vaccine field globally by evaluating the safety and immunogenicity of TB vaccines for all age groups that (1) prevent TB infection, (2) prevent progression from TB infection to disease, and (3) reduce the risk of unfavorable treatment outcomes, particularly treatment failure and recurrent TB, and post-treatment morbidity and mortality when used adjunctively with TB treatment. 

SAC6. To regularly exchange information progress and plans with basic researchers, particularly those working with preclinical animal models, especially nonhuman primates, to maximize the insights required to advance the HIV vaccine field.

SAC7. To utilize research on epidemiological, behavioral and social sciences to optimize the outcome of HIV vaccine research, including vaccine acceptability, regimen adherence, and community engagement. To utilize the HIV epidemiology of communities within which we work to optimize the recruitment, enrollment and retention of participants into HVTN protocols and to define the behavior and societal factors that affect the participation in HIV vaccine trials.