Strong Vaccine Science Foundation Advances COVID-19 Research

Anthony Fauci says vaccine developers can build on many years of research to stay ahead of SARS-CoV-2 variants

Published February 02, 2021

By Alan Dove

As concerns swirl around the emergence of novel variants of the SARS-CoV-2 coronavirus, Anthony Fauci, Director of the National Institutes of Allergy and Infectious Diseases, points to reassuring results from both clinical and laboratory tests, and underscored the ability of scientists to adapt rapidly to the evolving pandemic.

The new variants, one first isolated in the UK and one in South Africa, carry mutations in the gene encoding the spike protein that all of the currently approved and candidate vaccines target. Preliminary experiments have shown that some of the antibodies patients raise in their bodies against the spike protein don’t bind as well to the variant forms.

Speaking at a New York Academy of Sciences symposium, The Quest for COVID-19 Vaccines, Fauci explained that “the diminution [in binding] is about five or six fold,” but remains within the range expected to be protective. He added that real-world clinical trial data backs that up, with the latest results from Johnson & Johnson’s COVID-19 vaccine showing 85% efficacy in preventing severe disease even in a South African cohort where most of the cases involved one of the feared variants.

Building Upon Decades of Previous Research

At the same time, decades of prior work have positioned vaccinologists well to respond quickly if the virus does evolve to circumvent vaccine-mediated immunity. Indeed, the COVID-19 vaccine development effort to date has already illustrated how fast that response can happen. Less than a year after the first genome sequence of the SARS-CoV-2 coronavirus was published, millions of people around the world were receiving highly effective vaccines, a result Fauci calls an “extraordinary historic accomplishment.”

Putting this astonishing achievement in perspective, Fauci compared it to previous vaccine efforts. “Even as we developed more technologies, measles, for example, took ten years, hepatitis B took sixteen years, but…COVID-19 took 11 months,” said Fauci. The new pandemic vaccines were in fact decades in the making, building on a scientific legacy that is also helping researchers prepare to address new viral variants.

Tracing the history of the current crop of COVID-19 vaccines back to work on HIV vaccines in the 1990s, Fauci described the basic and applied science that built a system spring-loaded to respond to a pandemic. “Then along came SARS-CoV-2, and again, [through] that same work that dates back years, the marriage between vaccinology and structure-based vaccine design” quickly revealed the most promising antigen target for COVID-19 vaccines.

Structure-Based Design

In structure-based design, scientists begin with the atomic structure of an antigen, and predict how modifications to it could enhance its potency. For SARS-CoV-2, that process identified a specially modified version of the virus’s spike protein as the best antigen; that antigen is now the basis for nearly all currently approved and candidate COVID-19 vaccines. A parallel body of work had shown the capabilities of modern vaccine platforms such as messenger RNA, recombinant proteins, and genetically engineered viral vectors.

As the new vaccines finished preclinical trials early in 2020, their developers already had access to an established network of clinical trial sites.

“The extraordinary investments that were made decades ago in putting together the HIV clinical trial network was immediately adapted, by using many of these sites [as] part of the COVID-19 Prevention Network,” said Fauci, adding that the first phase 1 clinical trial began just over 60 days after the release of the SARS-CoV-2 genome sequence, a head-snapping speed for clinical development.

Effectively Combatting New Variants

Turning to the new variants originally seen in the UK and South Africa, now known as B.1.1.7 and B.1.351 respectively, Fauci added that the nature of the new vaccines’ underlying technologies will also make them relatively straightforward to update if necessary.

“Multiple companies…are now doing an upgraded version of their vaccines, which would likely serve as a boost,” said Fauci.

Regulatory authorities are already pondering how to handle such booster vaccines, but they may be able to accept an abbreviated approval process similar to the one used for seasonal flu shots. In that approach, the new boosts “would be considered by the FDA as literally a strain change,” subject to only two phases of safety and immunogenicity tests instead of full-scale phase 3 trials, said Fauci.

Efficacy versus Effectiveness

The vaccine effort also now faces obstacles that are harder to address through science and technology. Fauci contrasted the ideas of efficacy and effectiveness of a vaccine. While the former can be calculated from clinical trial data, the latter stems from how widely a community adopts the vaccine; a highly efficacious vaccine that few people get will fail to curb the virus’s spread.

“One of the challenges that we are facing [is apparent] if you look at the intent to get COVID-19 vaccines,” said Fauci, pointing to surveys that show that significant numbers of Americans remain hesitant about vaccination. “We need to respect that, but we need to try and convince them of the importance, for their own safety and the safety of their family and the American public, to get vaccinated,” he added.

Though he has made a preliminary estimate that “herd immunity,” or overall protection of the population, could require vaccination of 70-85% of the population, Fauci cautioned that those figures are just an educated guess; only long-term monitoring of infection rates will reveal when the country is effectively protected.