A New Model for Catalyzing Translational Science: The Early Stage Investigator Mentored Research Scholar Program in HIV Vaccines

Abstract

Engagement of early stage investigators (ESIs) in the search for a safe and effective vaccine is critical to the success of this highly challenging endeavor. In the wake of disappointing results from a large‐scale efficacy trial, the HIV Vaccine Trials Network (HVTN) and Center for HIV/AIDS Vaccine Immunology (CHAVI) developed a novel mentored research program focused on the translation of findings from nonhuman primate studies to human trials of experimental vaccines. From 2008 to 2011, 14 ESI Scholars were selected from 42 complete applications. Post program surveys and tracked outcomes suggest that the combination of flexible funding, transdisciplinary mentorship, and structured training and networking promoted the scientific contributions and career development of promising ESIs. Embedding a multicomponent research program within collaborative clinical trial networks and research consortia is a promising strategy to attract and retain early career investigators and catalyze important translational science.

Introduction

The search for a safe and effective HIV vaccine is one of the most challenging biomedical research endeavors of our time. Merck, Inc. (Whitehouse Station, NJ, USA) developed a promising recombinant adenovirus subtype 5‐based HIV vaccine candidate that was efficacious in protecting nonhuman primates (NHP) against a challenge with pathogenic chimeric simian and human immunodeficiency virus, and early human clinical trials demonstrated it was safe and immunogenic. Despite these promising results in the NHP model, the 3,000 person efficacy trial, known as the Step Study, showed that the vaccine failed to prevent infection or reduce viral load, and may have increased susceptibility to infection in a subgroup of participants.1

In the wake of these disappointing results, NIAID convened a Vaccine Summit that highlighted the apparent gap between preclinical and clinical research and the need to more effectively apply findings from NHP models to human trials. Given the projected long road ahead for vaccine discovery, the Summit focused on ways to bridge this gap, attract new minds, and catalyze ideas.2

The HIV Vaccine Trials Network (HVTN) and the Center for HIV/AIDS Vaccine Immunology (CHAVI), a consortium of HIV investigators, sought to address gaps in HIV vaccine R&D by creating a novel early stage investigator (ESI) mentored research program. The ESI Scholar Program was designed to attract a cadre of promising young investigators with an interest in NHP research and a desire to translate findings to HIV vaccine development. Below we describe the components of the program, scholar outcomes, and lessons that can be applied to other programs to attract the next generation of clinical translational scientists.

Methods

Program overview

From 2008 to 2012, HVTN and CHAVI recruited three cohorts of scholars. Scholars proposed 1–2 year translational research projects under the guidance of two senior scientists, one with expertise in NHP and the other clinical vaccinology. Budgets were limited to $250,000 per year for two years or $450,000 per year for resource‐intensive NHP experiments.

Mentoring and training

Scholars completed a training needs assessment and, with aid from mentors, documented expectations in a Scholar–Mentor Agreement, based on mentoring literature.3, 4 Peer mentoring was encouraged through networking receptions and workshops during semiannual HVTN and CHAVI meetings. Customized trainings included statistics, host genetics, NHP challenge models, and a professional development series on starting a laboratory, securing funding, and work–life balance. The range of training topics also tried to address the unique qualities representative of the generations of scholars and mentors.5

Program evaluation

We developed a logic model as a framework for program evaluation and assessed scholar and mentor satisfaction and perceived strengths and weaknesses.6 We surveyed scholars and mentors mid‐project and after completion. Key career‐development milestones were tracked and updated annually through June 2014.

Results

Program participants

Overall, we received 42 applications from 25 institutions. Most candidates were postdoctoral fellows or assistant professor‐level faculty. Applications were peer reviewed; 14 ESIs (33% of applicants) were selected to receive funding (five, four, and six scholars in three cohorts, respectively). In total, 24 mentors participated over 5 years, representing 15 institutions. Funded projects spanned a wide range of translational research including protective immune responses in breast milk and neutralization sensitivity of simian immunodeficiency founder viruses. The program fostered communication between two groups (the preclinical and clinical scientific communities), and trained a new cadre of scientists fully conversant in NHP research and clinical HIV vaccine trials.

Table 1 summarizes program inputs and scholar outcomes. To date the ESI Scholars have published 29 first‐author publications, 74 additional coauthored manuscripts, and presented 64 abstracts resulting from their ESI project results. Since ESI award, scholars received 24 independent grants totaling $6.2 million, with an additional $23.1 million in co‐investigator awards, totaling $29.3 million. The average age for first RO1 among three program alumni was 37, much lower than the national average of 42.7 One scholar has since become a research mentor for a minority medical student in a separate HVTN scholar program,8 and another scholar received the notable Presidential Award for Early Career Scientists. Of 14 scholars, 13 are currently working in clinical trials research (11 in academic settings, two at pharmaceutical companies) and one has an academic training position.

Table 1.

Key program components and outcomes from the HVTN/CHAVI ESI Scholar Award.

Program inputs	Number	Funding
Projects funded	14	$3.5 million/year
Review board members	25
Preclinical and clinical mentors	24
Webinars	7
Training workshops	4
Networking receptions	10
HVTN conference presentations	14
Program outcomes	Number	Funding
Promotions and appointments†	14
Manuscripts published*	103
1st Author manuscripts	29
Coauthor manuscripts	74
Abstracts/presentations*	64
Patent pending*	1
New grants awarded†	42	$29.3 million
PI grants awarded†	24	$6.2 million
R01	3
R21	4
R03	1
K08	1
P30, P50, P51	4
DP2	1
CFAR	3
Other	7
Coinvestigator awards†	18	$23.1 million
R01	2
R21	1
Gates	3
Other	12

*Resulting from work funded by scholar award.

^†Since initial selection as scholar.

Evaluation

Almost all scholars (93%) and most mentors (71%) completed program exit surveys. Scholars were satisfied with the program—11/14 were “very satisfied” and 3 were “satisfied.” Ten of 14 surveyed scholars intend to stay in HIV vaccine research. All reported the program helped develop their career, increased their knowledge of HIV vaccine research, and resulted in a project that they believed offered a unique contribution to the field. Open‐ended responses revealed that mentoring, training, networking, and career development opportunities were important program strengths; some suggested that the project duration be lengthened.

All mentors reported they planned to continue mentoring their scholar beyond the program period and concurred with scholars about the unique contributions made through the funded research. Mentors advocated to continue the program and, if funding permitted, projects could extend beyond 2 years.

Discussion

The HVTN/CHAVI ESI Scholar Program offers a promising new model that combines interdisciplinary‐mentored research and career development activities that could be replicated by other research groups engaged in team science. A constellation of venues for scholar–mentor engagement were important for fostering successful collaborations and productive research. Clinical trial networks and/or research consortia are well suited to organize such programs given their ability to leverage broad research portfolios, a critical mass of available mentors, and sufficient administrative infrastructure. The average time from application submission to notification was 6 weeks, substantially faster than the standard review cycle for NIH grants and highly relevant as constrained federal funding limits flexible funding opportunities to help postdoctoral candidates transition to junior faculty.7, 9 While the ESI Program did not reimburse mentors for their time, sustainability of programs that rely on a core group of transdisciplinary mentors, a key strength of other HIV mentoring programs,10 may require ongoing investment.4

Conclusion

A multicomponent, mentored research program implemented within large research networks/consortia is feasible and may catalyze translational science while developing the careers of promising ESIs.