Pfizer CSO on UK COVID Variant and mRNA Vaccine Development to Fend Off the Flu

The speed with which safe and effective vaccines have been developed against SARS-CoV-2—the novel coronavirus responsible for the COVID-19 global pandemic—is unprecedented. Less than a year after SARS-CoV-2 triggered an international public health crisis, scientists delivered the first vaccines. They overcame many scientific, technological, and organizational hurdles in the race to bring vaccines from the lab to the clinic. While we celebrate their achievements, we must also rely on scientists to answer many remaining questions about COVID-19 epidemiology, efficacy in ongoing clinical trials, different responses among people in some at-risk groups, ways to improve vaccine distribution, and approaches we might use to prepare for future pandemics.

Annaliesa Anderson, PhD, the Vice President and CSO of Bacterial Vaccines at Pfizer, recently responded to some of our questions about the efficacy of Pfizer’s COVID-19 vaccine against new viral variants, future pandemics, and other viral targets for mRNA vaccines.

The recent emergence of a novel coronavirus variant in the UK has highlighted the rapid rate at which the virus mutates. Can you explain how vaccine-induced immunity might be protective against multiple variants?  

Anderson: SARS-CoV-2 contains four major structure proteins, including the spike (S) protein. This protein is embedded on the virus surface and is critical for viral entry into human cells. One of the strengths of a vaccine is that when we receive a dose, we generate polyclonal antibody responses. That is, we expect our immune system to see the entire antigen or protein, and this results in antibodies being made that can recognize all of it. In contrast, a monoclonal antibody response would only recognize one region on the protein. A protein such as the SARS-CoV-2 spike protein can only mutate so much before it loses its function, so polyclonal antibodies induced by a vaccine that encodes the optimized SARS-CoV-2 full-length spike (S) protein are much less likely to be impacted by small mutations in the viral spike protein than a monoclonal antibody. Pfizer and BioNTech have found that they can neutralize test viruses that have a variety of mutations found in circulating viruses.

SARS-CoV, MERS-CoV (the virus that causes Middle East respiratory syndrome) and SARS-CoV-2 are all viruses from the large, very diverse Coronaviridae family. Humans seem to be particularly susceptible to respiratory illnesses caused by these viruses. Will the next widespread, virulent illness be caused by another coronavirus and is there a way to prepare for it?  

Anderson: You are right, over the last 20 years we are seeing increasing threats from members of the Coronaviridae family (containing coronaviruses) and we can’t rule out future risks from this or other viruses that we have seen increase in prevalence over recent years such as dengue virus, Zika virus, Chikungunya virus, and even new strains of the influenza virus. The good news is that we have seen how quickly we can mobilize to fight against an emergent virus; however, it is hard to predict which virus may cause a problem. There is still a gap when it comes to how we treat these infections, which is why we also need to be looking at developing therapeutics that can be used across the Coronaviridae family. At the same time the global scientific community needs to be diligent about surveillance so we can quickly deploy the appropriate tools in case of new threats emerging.

The speed with which SARS-CoV-2 vaccines have been developed is stunning—it’s over twice as fast as the development time for the SARS-CoV (the virus that causes SARS) vaccine.  What additional progress would you like to see made for the development of additional SARS-CoV-2 vaccines and to prepare for future pandemics?

Anderson: The vaccines currently authorized, approved, or in development have been developed with deliberate speed. In the case of the Pfizer BioNTech vaccine, steps were conducted in parallel instead of sequentially as - is traditionally done, and our ability to accumulate cases in our study population was aided by the high attack rates in places where we were conducting our clinical trials. We look forward to continuing our work to optimize our COVID-19 mRNA vaccine to potentially have a formulation that is stable at refrigerator temperatures.

As of December 2020, the FDA authorized two vaccines for SARS-CoV-2, from Pfizer and Moderna – both mRNA vaccines.  mRNA vaccines are a new, potent, and low cost type of vaccine. Can you tell us what other mRNA vaccines Pfizer may be developing?   

Anderson: Pfizer and BioNTech entered into a research collaboration agreement in 2018 to develop a vaccine to help prevent influenza.  One of the reasons Pfizer and BioNTech chose to utilize an mRNA platform is because of the potential for the flexibility of the technology in comparison to traditional vaccine technologies. This flexibility includes the ability to alter the mRNA sequence in the vaccine to cover new strains.

Now that we have demonstrated that the COVID-19 vaccine is safe and effective, we will be looking to see if we can develop an mRNA-based vaccine against influenza. As flu is a seasonal disease, and we require a new vaccine as often as each flu season due to the high number of antigenically distinct strains of influenza virus, we believe that the RNA technology lends itself very well for this type of vaccine due to the speed at which the vaccines can be updated when each season’s influenza vaccine strains are recommended.

Beginning on February 2, 2021, the New York Academy of Sciences will host a 2-day conference, “The Quest for a COVID-19 Vaccine”, which will bring together scientists from academia, biotechnology, and government, including keynote speakers Anthony Fauci, MD, Director of the National Institute of Allergy and Infectious Diseases and White House Coronavirus Task Force, and Moncef Slaoui, PhD, formerly the Chief Scientific Advisor of Operation Warp Speed, to discuss these questions and more.  Register today here.

Disclosure: The scientific conference “The Quest for a COVID-19 Vaccine” is supported, in part, by Pfizer, Inc.