Amidst the tumult in the nation’s capital, a quieter reckoning was taking place this week for the Moderna COVID-19 vaccine clinical trial. Lab Land has been hearing from Emory-affiliated study participants that they’re finding out whether they received active vaccine or placebo.
For example, Emory and Grady physician Kimberly Manning, who had written about her participation in the Moderna study in a Lancet essay, posted on Twitter Tuesday. She discovered she had received placebo, and then was offered active vaccine.
After Moderna reported strong efficacy and an Emergency Use Authorization came from the FDA, this was going to happen at some point – the question was when and how. At the advisory panel hearing in December, there was some tension over whether to remove the blind immediately, as this STAT article describes:
“Companies have said that they feel an ethical obligation to deliver vaccine to placebo recipients; the FDA and experts at its advisory panel have debated whether this obligation even exists. Instead, they argue, offering vaccine to volunteers receiving placebo limits the quality of the data about the vaccine’s long-term efficacy and side effects.”
A plan to keep participants in the study under a blinded crossover design was floated, but not implemented. Some participants have said they sensed from the start, based on temporary unpleasant side effects, whether they had received active vaccine or placebo.
At the American Association for the Advancement of Science meeting in Boston last weekend, Emory Vaccine Center researcher Mark Mulligan presented some limited findings on immune responses in Zika-infected humans, who were returned US travelers or expatriates.
The results were intriguing, despite the small number of study participants: five, two of whom were pregnant. Detailed information has not been available about immune responses against Zika in humans, especially T cell responses.
Highlights from Mulligan’s abstract:
*All five seemed to have a hole in their immune systems – functional antiviral “killer” CD8 T cells were rare, despite activation of CD8 T cells in general and strong responses from other cell types.
*Cross-reactive immune responses, based on previous exposure to dengue and/or yellow fever vaccine, may have blunted Zika’s peak.
*”Even with prolonged maternal viremia, both pregnancies resulted in live births of apparently healthy babies.” Read more
Vaccine researchers have developed a strategy aimed at generating broadly cross-reactive antibodies against the influenza virus: embrace the unfamiliar.
In recent years, researchers interested in a “universal flu vaccine” identified a region of the viral hemagglutinin protein called the stem or stalk, which doesn’t mutate and change as much as other regions and could be the basis for a vaccine that is protective against a variety of flu strains.
In an Emory Vaccine Center study, human volunteers immunized against the avian flu virus H5N1 readily developed antibodies against the stem region of the viral hemagglutinin protein. In contrast, those immunized with standard seasonal trivalent vaccines did not, instead developing most of their antibodies against the more variable head region. H5N1, regarded as a potential pandemic strain, is not currently circulating in the United States and the volunteers had not been exposed to it before.
The results were published Monday, August 25 inÂ PNAS.
The key to having volunteers’ bodies produce antibodies against the stem region seemed to be their immune systems’ unfamiliarity with the H5N1 type of virus, says lead author Ali Ellebedy, PhD, postdoctoral fellow in the laboratory of Rafi Ahmed, PhD, director of Emory Vaccine Center and a Georgia Research Alliance Eminent Scholar.
Note: for a counterpoint, check out this 2013 Science Translational Medicine paper on how vaccination that induces anti-stem antibodies contributes toÂ enhanced respiratory disease in pigs.
Paula Frew, PhD
The scientific part of the AIDS Vaccine 2010 meeting began Tuesday evening with an exciting summary of issues facing the field from NIAID director Tony Fauci. But before that, participants in this yearâ€™s conference got a chance to warm up with several â€œsatellite sessions.â€
One of them, â€œEffective Community Engagement in HIV Vaccine Research Among Communities and Researchers,â€ was organized by Paula Frew, PhD, director of health communications and applied community research at Emoryâ€™s Hope Clinic.
Two prominent themes emerged from this session. The first was that community members should be involved in clinical trials at every step of the process: from design and recruitment to dissemination of results.
â€œIn the past, scientists often came to the community late in the process, after a protocol for a study was already approved, and said: â€œWill you support what weâ€™ve already decided?â€ said Steve Wakefield of HIV Vaccine Trials Network. â€œThis doesnâ€™t work.â€
The Joint United Nations Programme on HIV/AIDS and AVAC presented proposed guidelines for â€œgood participatory practice,â€ analogous to good clinical practices.
Another theme that emerged from the satellite session was the search for more flexible â€œadaptiveâ€ clinical trial formats. Glenda Gray from South Africaâ€™s University of the Witwatersrand emphasized that adaptive trials could be faster and avoid enrollment of large numbers of patients unnecessarily.
Riders gather at the Hope Clinic of the Emory Vaccine Center for the final leg of their ride.
More than 130 bicyclists rode 200 miles in two days to raise $188,660 for AIDS vaccine research at the Emory Vaccine Center. The AIDS Vaccine 200 on May 22-23, sponsored by Action Cycling Atlanta, was the eighth annual ride. The series now has raised more than $680,000 for AIDS vaccine research.
This year’s riders traveled from Emory to Eatonton, Georgia, and back to Emory along with a volunteer crew.
Because of generous sponsorships, Action Cycling donates 100 percent of funds raised by participants to AIDS vaccine research. These unrestricted funds fill gaps that cannot be met by grant dollars alone.
Posted on June 11, 2010
Paula Frew, PhD, MPH
Although African Americans make up a significant share of HIV cases in the U.S., they are underrepresented in HIV clinical trials. New research shows that promotion of HIV clinical trials and participation by African Americans can be increased by coalitions that link community organizations to clinical-research institutions.
â€œCommunity organizations already have built trusting relationships in their communities,â€ saysÂ Paula Frew, PhD, assistant professor of medicine at Emory School of Medicine. â€œIf HIV/AIDS prevention and HIV clinical research become part of the agendas of these organizations, they can become ideal allies for increasing participation by community members who are at risk for disease.â€
Frew was lead investigator in a study published recently in the Journal Prevention Science. SheÂ is director of health communications & applied research at the Hope Clinic of the Emory Vaccine Center and an investigator in the Emory Center for AIDS Research (CFAR).