LA JOLLA, Calif.—As COVID-19 variants have begun to emerge, two leading scientists are asking health agencies to invest in the development of vaccines that would be broadly effective against many different variants and strains of potential pandemic viruses. Drs. Dennis Burton and Eric Topol of Scripps Research have published a commentary in Nature that calls on governments to provide significant funding support for rational vaccine design based on broadly neutralizing antibodies.
Broadly neutralizing antibodies provide broad-spectrum potency against viruses, a characteristic that opens the door to developing vaccines that could provide immunity against the many variants that can evolve from a fast-mutating virus. These antibodies also have the potential to be used for preventing and treating infections.
Burton and Topol note that the rapid development of effective vaccines against COVID-19 was possible due to certain properties of SARS-CoV-2—in particular the spike protein on the virus’s surface. But they warn that a virus driving the next pandemic may not provide such a ready target, which could substantially slow the process of developing a novel vaccine.
“In evolutionary terms, SARS-CoV-2 is an ‘evasion-light’ pathogen. It has not had to acquire an armamentarium of molecular features to outwit immune responses in general and neutralizing antibodies in particular. This is because it currently transmits from one person to another before immune responses have developed—and, in many cases, before disease symptoms are noted,” say Burton and Topol.
“Other pathogens are ‘evasion-strong’. The extreme example is HIV. It frequently co-exists with human immune systems, possibly for years, before onward transmission. So it has developed many ways to stymie our defenses, including extensive sequence variation,” they add, pointing out that “The emergence of another pathogen with the evasion capabilities of HIV might be the worse-case scenario for a pandemic.”
“There is also now initial evidence from two vaccine clinical trials suggesting reduced efficacy in preventing mild to moderate COVID-19 in individuals infected with the B.1.351 variant (seego.nature.com/2ydkrxs and go.nature.com/2musicv), although the vaccine candidates still seemed to prevent severe disease. Over time, uncontained spread and accelerated evolution in immunocompromised hosts could drive enough mutation to reduce the efficacy of current vaccines considerably, or even entirely,” Burton and Topol explain. “We would then need vaccines that induce antibodies able to neutralize variants of SARS-CoV-2, as well as the original virus.”
Burton and Topol call for a new approach to pandemic preparedness. They point to broadly neutralizing antibodies as a promising way to develop vaccines and therapies that could be readily adapted to viruses that can rapidly evolve and evade traditional vaccines.
“Such antibodies could be used as first-line drugs to prevent or treat viruses in a given family, including new lineages or strains that have not yet emerged,” write Burton and Topol. “More importantly, they could be used to design vaccines against many members of a given family of viruses.”
“Unlike a reactive program that swings into action when a new pathogen appears, our proposal has goals that can be described now and projects that could begin on a large scale immediately. Thanks to work already done on other viruses, particularly HIV and influenza, the approaches are understood and the infrastructure is in place,” they say. “Investments made so far in basic science—including virology, genomics, immunology and structural biology—have afforded us a remarkable opportunity to get ahead of further SARS-CoV-2 evolution and put us in a powerful position of readiness for new viral pathogens.”
Burton and his colleagues at Scripps Research and other organizations are currently working on developing vaccines based on broadly neutralizing antibodies, in pursuit of truly effective HIV vaccines. The researchers are also seeking to employ broadly neutralizing antibodies as therapies and vaccines against influenza, another evasive virus that is a prime contender for future pandemics.
“Such pan-virus vaccines could be made in advance and deployed before the next emerging infection becomes a pandemic. We call for an investment now in basic research leading to the stockpiling of broadly effective vaccines,” Burton and Topol conclude.
GlobalData, a leading data and analytics company, has also pointed out the importance of vaccine development that covers variants.
“The fast-spreading new COVID-19 variants may reduce the protective effects offered by the leading vaccines. As a result, researchers need to ascertain whether the vaccines are as effective against the new viral variants or if they require some level of modification to yield optimum immune response against the variants,” stated Mohamed Abukar, clinical trials analyst at GlobalData. “It is imperative that clinical research continues at the same pace to constantly evolve the current knowledge and adapt to new challenges such as new viral variants, and ultimately to produce a universal vaccine.”
