Vaccines Working Group

Charge

Accelerate the evaluation of vaccine candidates by supporting harmonized clinical efficacy trials and a parallel effort to generate biomarkers and other evidence for more rapid approval/authorization. The working group officially completed its charge as of July 31, 2020, but continues to meet on an ad-hoc basis to provide recommendations for ongoing vaccine trials.

Objectives

Check mark indicates completion.

✓ Vaccine Clinical Trials 

The working group coordinated and contributed to the development of harmonized protocols for vaccine evaluation in Phase 3 trials, which importantly allows for the simultaneous assessment of multiple vaccine candidates and the incorporation of new vaccines as they are available. Trials informed by the harmonized protocol for current Phase 3 vaccine studies and for future vaccine candidates are listed on the ACTIV Vaccines page.

✓ Human Challenge Studies

The working group published a Perspective for the New England Journal of Medicine that assess practical considerations and prerequisites for using controlled human infection models (CHIMs), which can be used for human challenge studies, to support SARS-CoV-2 vaccine development.  They conclude that conventional randomized controlled trials involving only natural exposure to SARS-CoV-2 are the fastest and most effective path forward for establishing vaccine safety and efficacy. Parallel development of CHIMs may provide complementary tools to address additional questions such as the duration of immunity and correlates of protection, if such studies can be conducted ethically.

✓ Protective Immune Responses

At the beginning of ACTIV, it was unclear whether there would be sufficient disease incidence in the second half of 2020 to enable expeditious clinical evaluation of vaccine efficacy. To prepare for that contingency, the working group discussed potential interim data packages before Phase 3 efficacy results to enable possible authorization/approval through mechanisms like FDA accelerated approval or Emergency Use Authorization. During the course of the program it became clear that incidence rates in some regions of the world have remained high, enabling relatively rapid clinical evaluation of efficacy. The working group also has contributed to plans for analyses of correlates of protection to enable the approval of future vaccines based on biomarker established through efficacy trials.

✓ Vaccine-Associated Immune Enhancement

The working group published a manuscript in Science Translational Medicine that provides an informed perspective on the historical experience with vaccine-associated enhanced disease (through immunopathologies and antibody-dependent enhancement) and the question of potential vaccine-associated enhanced disease in COVID-19 vaccine development.  

✓ Impact of Vaccines on Transmission

The Phase 3 vaccine efficacy trials primarily assessed the impact of vaccination on prevention of symptomatic COVID-19 disease, and secondarily measured an indicator of SARS-CoV-2 infection. The working group evaluated proposed study designs to directly evaluate the impact of vaccination on infection and transmission of SARS-CoV-2 infection by vaccinated participants and advised on plans to advance these studies.

Correlates of Protection

The working group identified the important role of correlates of protection in accelerating the evaluation of vaccine efficacy in populations outside those that participated in efficacy trials and of future vaccine candidates in the context of authorized or approved vaccines. Proposed approaches for correlates analyses were reviewed and studies are ongoing and are expected to also provide insights into vaccine efficacy against viral variants.

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