By Alvin Boyd Newman-Caro and Rebecca L. Sanchez, PhD

Will Flu Shots & COVID Vaccines Be Combined? What Would the Future Look Like?

By Alvin Boyd Newman-Caro and Rebecca L. Sanchez, PhD

The idea of combined vaccines is not a new one. There are several examples of combined vaccines currently utilized, such as Pediarix, ProQuad, Kinrix and Pentacel, all which protect against various combinations of diphtheria, tetanus, pertussis (DTaP), hepatitis B virus, poliovirus (IPV), measles, mumps, rubella (MMR), varicella virus (chickenpox) and Haemophilus influenzae type b (Hib).2 Not only have combination vaccines been proven effective, they also have the advantage of being an individually administered shot that protects against multiple diseases.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has produced 33,079,543 cases of coronavirus illness and taken 591,265 lives in the United States.1 When the outbreak began, prompt publication of the viral genome sequence allowed work to begin immediately on a vaccine solution. In groundbreaking fashion, vaccines for COVID-19 were created in less than one year. Up to this point, Pfizer/BioNTech has reported efficacy of 95%, while Moderna has set forth an efficacy of 94.5%.3,5 Nonetheless, it is unknown if current COVID vaccines will be protective against future COVID-19 strains. It is possible that SARS-CoV-2 will persist for some time and will potentially become a seasonal epidemic, like that of past influenza epidemics. Reasons for this are because we have yet to globally eliminate earlier strains of SARS-CoV-2, we are seeing novel viral variants emerge and the long-term protectiveness of current COVID vaccines remains unknown — calling into question the need for booster shots. Similar to the influenza virus, the SARS-CoV-2 viral variants could necessitate a modified yearly vaccine against it. Therefore, the next logical step in vaccine development would be the creation of a combined COVID and influenza vaccine. In addition, discussions involving COVID and influenza combination vaccines make sense right now, especially since the 2021-2022 influenza season is already upon us.

During this year’s typical influenza season, cases of influenza infections were significantly reduced. In May, the CDC reported on its website that from September 27, 2020, through May 15, 2021, only 250 (or 0.05%) of the 485,637 specimens tested and reported were positive for influenza viruses at U.S. public health laboratories, and only 1,874 (or 0.18%) of the 1,054,101 respiratory specimens tested and reported were positive for influenza viruses at U.S. clinical laboratories (compared with 10%-19% in recent years).6,7 However, now that mask and social distancing regulations are becoming more relaxed, a rise in both influenza and SARS-CoV-2 cases is predicted for the 2021-2022 season. Infection with influenza, SARS-CoV-2 or influenza/SARS-CoV-2 co-infection, presents a significant future public health threat, making a combination vaccine desirable.

While many are just starting discussions about future combination vaccines, Novavax, a biotechnology company developing a SARS-CoV-2 vaccine (NVX-CoV2373), released preclinical data in May 2021 using a combination hemagglutinin (HA) quadrivalent nanoparticle influenza vaccine (qNIV) and their COVID-19 vaccine candidate (NVX-CoV2373).4,5 The Novavax study

stated the following: “The combination qNIV/CoV2373 vaccine produces high titer influenza hemagglutination inhibiting (HAI) and neutralizing antibodies against influenza A and B strains. The combination vaccine also elicited antibodies that block SARS-CoV-2 spike protein binding to the human angiotensin converting enzyme-2 (hACE2) receptor. Significantly, hamsters immunized with qNIV/CoV2373 vaccine and challenged with SARS-CoV-2 were protected against…and were free of replicating SARS-CoV-2 in the upper and lower respiratory tract with no evidence of viral pneumonia. This study supports evaluation of qNIV/CoV2373 combination vaccine as a preventive measure for seasonal influenza and COVID-19.”4 And while this early data is promising, human-based clinical trial studies of the combination vaccine are still imperative for the Novavax study.

As vaccine research continues to develop and trials increase in number, an immunization action plan needs to be considered. In addition, the cost and burden of individual shots as opposed to a combination vaccine requires evaluation, while also keeping in mind that citizens in rural areas and underserved populations would likely benefit from a combination vaccine due to its convenience and enhanced protection against both SARSCoV-2 and influenza viruses.

What would the future look like?

The future of any novel COVID/influenza combination vaccine is still undetermined; nevertheless, we can analyze past vaccination trends to predict future ones. Multiple scenarios can be proposed regarding a patient’s choice for vaccination:

1. Patients who get the influenza vaccine yearly will continue to receive the influenza vaccine and will more than likely also opt to receive the COVID vaccine. In this scenario, the COVID/influenza combination vaccine may be preferred since it is more convenient to receive one combined shot rather than two individual shots.

2. Patients who get the influenza vaccine yearly will continue to receive the influenza vaccine but may refuse the

COVID vaccine due to hesitation to receive a newly synthesized vaccine or the inconvenience of returning for a required second COVID vaccine dose, depending on the type of vaccine first administered.

3. Patients who decline both vaccines because of anti-vaccination sentiments, vaccine hesitations, lack of health care access or any number of barriers to health care.

4. Patients who choose only to receive the

COVID vaccine because of pre-existing hesitations from past influenza vaccine experience (i.e., those who believe “the last time I received the influenza vaccine,

I got the flu”).

Taken together, ongoing research is suggesting that influenza and SARS-CoV-2 present with many similarities. Both respiratory viruses demonstrate the need for a yearly vaccine based on variations in viral strains from past strains. They also manifest parallelism in symptoms, transmission and populations that are particularly vulnerable. Therefore, a combination vaccine presents the optimal solution to curbing both infections. While research is newly emerging regarding a combination vaccine, past infection and vaccination trends also show a promising future for a combined influenza and SARS-CoV-2 vaccine. For these reasons, public health officials and members of the health care community should consider starting a conversation now around combination vaccine implementation. References 1. “CDC COVID Data Tracker.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, covid.cdc.gov/covid-data-tracker/#cases_totalcases. 2. “Combination Vaccines – Fewer Shots Same Protection.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 1 Aug. 2019, www.cdc.gov/vaccines/parents/why-vaccinate/combination-vaccines.html. 3. Kim, Jerome H., et al. “Looking beyond COVID-19 Vaccine Phase 3 Trials.” Nature Medicine, vol. 27, no. 2, 2021, pp. 205–211., doi:10.1038/s41591-021-01230-y. 4. Massare, Michael J, et al. “Combination Respiratory Vaccine Containing Recombinant SARS-CoV-2 Spike and Quadrivalent Seasonal Influenza Hemagglutinin Nanoparticles with Matrix-M Adjuvant.” 2021, doi:10.1101/2021.05.05.442782. 5. Shinde, Vivek, et al. “Efficacy of NVXCoV2373 Covid-19 Vaccine against the B.1.351 Variant.” New England Journal of Medicine, vol. 384, no. 20, 2021, pp. 1899–1909., doi:10.1056/nejmoa2103055. 6. Uyeki, Timothy M., et al. “Influenza Activity in the US During the 2020-2021 Season.” JAMA, 2021, doi:10.1001/ jama.2021.6125. 7. “Weekly U.S. Influenza Surveillance Report.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 28 May 2021, www.cdc.gov/flu/ weekly/index.htm.

Alvin Boyd Newman-Caro is a Fourth Year Medical Student at the University of Incarnate Word School of Osteopathic Medicine. He plans to specialize in General Surgery.

Rebecca L. Sanchez, PhD is an Assistant Professor of Microbiology at the UIWSOM.