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The escalating arms race between viruses and humans: Why a universal coronavirus vaccine is so critical

The arrival of the next pandemic is a matter of when, not if

COVID-19 was the third major and serious coronavirus epidemic or pandemic following SARS in 2002 and MERS in 2012,” said researcher Dr. Peter Hotez, dean of Baylor College’s National School of Tropical Medicine and co-director of the Texas Children’s Hospital Center for Vaccine Development. “We should anticipate a fourth coronavirus outbreak within the next decade or so,” 

To prepare for the inevitable, we will need government-funded basic science in universities and the collaboration of drug companies experienced in vaccine research and development. A “universal” vaccine — one that protects against infections by both existing and new variants — would be an important advance.

We have learned a lot about the SARS-CoV-2 virus during the more than four years since the COVID-19 plague shook our world. Because the virus replicates its RNA and mutates in every infection, its spike proteins keep on changing. Thus, by the time a vaccine targeting a specific spike protein becomes available, a new variant of the virus with a new spike protein is likely to have emerged, one that might be more transmissible or cause more severe disease, or both.

New viral variants such as the original Omicron and the many subtypes descended from it were less susceptible to the vaccines developed to protect against the original Wuhan SARS-CoV-2. Moreover, even when the vaccine and virus are a good match, protection from the vaccine (at least from those developed until now) wanes substantially with time. 

For those reasons and because uptake of the newest round of vaccines has been anemic in the U.S., we are still experiencing almost 10,000 COVID hospitalizations per week. Fortunately, the numbers of COVID-related emergency visits, hospitalizations, deaths, and levels of SARS-CoV-2 in wastewater (an early predictor of future COVID infections) are trending downward, a cause for cautious optimism. But there are still many new cases occurring, and the SARS-CoV-2 virus continues to replicate, mutate, and evolve.

Although we are far below the COVID peaks during the height of the pandemic, there are reasons for concern about the future – especially the increasing ability of successive SARS-CoV-2 variants of concern to escape immunity from both natural infection and vaccination, and the risk of spillovers of various animal coronaviruses into humans. For example, a 2015 article in Nature Medicine by an international group of researchers described the peril posed by a SARS-like virus, SHC014-CoV, and concluded that there was “a potential risk of SARS-CoV re-emergence from viruses currently circulating in bat populations.” Other coronavirus researchers have expressed similar concerns over the past decade.

Prospects for developing a universal vaccine

We need to be prepared for the emergence of new SARS-CoV-2 variants and other pandemic viruses. Key is the development of new vaccines that are as close as possible to a “universal vaccine” that would protect against multiple types of coronaviruses. Several approaches are being taken, including:

  • modifying adenoviruses as a vector for vaccine antigens;
  • using ferritin nanoparticles and self-amplifying RNA (which works similarly to messenger RNA (mRNA) except that it can replicate itself once inside the cells of the body);
  • incorporating many different fragments of the SARS-CoV-2 virus’ spike proteins, which the virus uses to bind to human cells and gain access to elicit a broader immune response;
  • focusing on parts of the virus that have been highly conserved – that is, that do not tend to mutate – in the variants of concern that have arisen up to now.   

Caltech Professor Pamela Bjorkman and her colleagues have used the multiple-spike-proteins approach with some preliminary success. They have presented the immune system – in animal models, to this point – with fragments of the spike proteins from SARS-CoV-2 and seven other SARS-like betacoronaviruses that have been attached to a protein nanoparticle, forming a structure that induces the production of a broad spectrum of cross-reactive antibodies. Early results showed that antibodies elicited by this synthetic vaccine were able to bind not only to the eight coronaviruses whose spike proteins are represented on the nanoparticle, but to four additional coronaviruses not present in the vaccine.  

Another important finding was that “when vaccinated with this so-called mosaic nanoparticle, animal models were protected from an additional coronavirus, SARS-CoV, that was not one of the eight represented on the nanoparticle vaccine” (emphasis in original). That implies that the vaccine might protect against subvariants of SARS-CoV-2 that have not yet appeared.

The group reported that the vaccine appeared to protect mice and monkeys that had been exposed to an array of coronaviruses. Professor Bjorkman hopes to have a vaccine in clinical trials this year.

U.S. Army medical researchers are also making important advances, developing a nanoparticle that elicits neutralizing antibodies against the original (Wuhan) SARS-CoV-2 virus and subsequent variants of concern, as well as against SARS-CoV, the virus that caused the SARS outbreak 20 years ago. Their vaccine elicited immune responses that rapidly eliminated replicating virus in the upper and lower airways and lung tissue of nonhuman primates after high-dose SARS-CoV-2 virus challenge. They have a vaccine in an early clinical trial.

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Illustration of a nanoparticle vaccine that contains proteins from many different flu strains. Credit: UW Medicine Institute for Protein Design

Yet another recent approach is being taken by a multinational group of academic and industry researchers who used a “viral-genome-informed computational method for selecting immune-optimized and structurally engineered antigens” to identify an antigen structure that elicited broad-based immune responses against different members of a large group of naturally-occurring SARS and SARS-CoV-2-related viruses. They showed that “a single antigen based on the receptor binding domain of the spike protein elicits broad humoral responses against SARS-CoV-1, SARS-CoV-2, and two other viruses in mice, rabbits and guinea pigs.” Phase 1 clinical trials are underway in England.

Substantial amounts of public and private research funding are being made available for ongoing work on such vaccines. The Coalition for Epidemic Preparedness Innovations (CEPI) has provided initial funding of around $200 million, which the NIH supplemented with $36 million. However, those expenditures won’t begin to cover the costs of the clinical trials required and fall far short of the approximately $10 billion spent by the Trump Administration on Operation Warp Speed, which was instrumental in developing the first round of COVID vaccines in 2020 in record time. 

Some of that slack will likely be addressed by U.S. Department of Health and Human Services funding of more than $500 million for the development of next-generation COVID-19 vaccines, which is part of the government’s $5 billion Project NextGen. Its areas of focus include vaccines that are easier to administer and produce longer and more robust protection, and the development of new technologies that will enable faster, cheaper, and more flexible production of vaccines.

Another pandemic will occur. The key question: Will we have done the extensive research necessary to limits its potentially catastrophic impact? To be prepared. we need government-funded basic science in universities and the collaboration of drug companies experienced in vaccine research and development. 

Henry I. Miller, a physician and molecular biologist, is the Glenn Swogger Distinguished Fellow at the American Council on Science and Health. He was the founding director of the FDA’s Office of Biotechnology. Find Henry on X @HenryIMiller

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