Beyond mRNA: A Pharmacist’s Guide to the Full COVID-19 Vaccine Landscape

Since the introduction of COVID-19 vaccines, messenger RNA (mRNA)–based vaccines have played a central role in COVID-19 prevention efforts in the United States.¹ However, mRNA vaccines represent only one approach among several vaccine platforms developed to protect against SARS-CoV-2 infection.¹ Protein subunit, viral vector, and inactivated virus vaccines have all contributed to global vaccination efforts and remain relevant when counseling patients about vaccine selection, safety concerns, and prior vaccination experiences.^1,2

Although COVID-19 is no longer a public health emergency, it remains a significant cause of morbidity and mortality, particularly among older adults and individuals with underlying medical conditions.^1,2 As recommendations continue to evolve, pharmacists increasingly encounter patients who have questions about vaccine technologies, concerns regarding adverse effects, or interest in switching from one vaccine type to another.² Understanding the differences between available vaccine technologies can help pharmacists provide evidence-based recommendations and individualized counseling.

Understanding the Vaccine Platforms

mRNA Vaccines

mRNA vaccines, including Comirnaty (Pfizer-BioNTech), Spikevax (Moderna), and mNEXSPIKE (Moderna), deliver mRNA that enables host cells to temporarily produce the SARS-CoV-2 spike protein. The immune system recognizes this protein as foreign and generates both antibody and T-cell responses.^1,2 This process helps establish immunologic memory that can facilitate a more rapid response upon future exposure to the virus.^1,2

Clinical trials and real-world data have demonstrated strong protection against severe COVID-19 outcomes with mRNA vaccines, including hospitalization and death.^3,4 Common adverse effects include injection site pain, fatigue, headache, fever, and myalgia.^3,4 Rare cases of myocarditis and pericarditis have been reported, particularly among adolescent and young adult males, although these events remain uncommon and are generally less severe than cardiac complications associated with COVID-19 infection itself.⁵

A common counseling point involves correcting the misconception that mRNA vaccines alter DNA. Pharmacists can reassure patients that mRNA does not enter the cell nucleus and is rapidly broken down after protein production. The mRNA serves as a temporary blueprint for spike protein production and does not alter a person’s genetic material.¹ Misunderstandings regarding the interaction between mRNA and human DNA is a common source of vaccine hesitancy and can often be resolved with a brief, clear explanation of how the vaccine works.

Protein Subunit Vaccines

Protein subunit vaccines use purified portions of a pathogen rather than genetic material. The Nuvaxovid vaccine (Novavax) contains laboratory-produced spike protein nanoparticles combined with an adjuvant that enhances immune responses. The inclusion of an adjuvant is an important component of this vaccine platform, as it enhances immune recognition of the spike protein.⁶

This platform may be more familiar to some patients because similar technology has been used for decades in vaccines such as hepatitis B vaccines. Protein subunit vaccines generate robust antibody responses while maintaining a favorable safety profile.⁶ For individuals who remain hesitant about mRNA vaccines, the availability of a protein-based alternative may increase willingness to receive COVID-19 vaccination. As a result, protein subunit vaccines represent an important addition to the range of available COVID-19 vaccine options.

Viral Vector Vaccines

Viral vector vaccines use a modified, nonreplicating virus to deliver genetic instructions for production of the SARS-CoV-2 spike protein. Viral vector COVID-19 vaccines include the now-discontinued Janssen vaccine and several internationally available products that utilize adenoviral vector technology.⁷ These vaccines stimulate both humoral and cellular immune responses and demonstrated effectiveness against severe COVID-19 outcomes during earlier stages of the pandemic.⁷

Reports of thrombosis with thrombocytopenia syndrome following administration of certain viral vector vaccines prompted revisions to vaccine recommendations and contributed to the decreased use of these products in several countries, including the US.⁸ Although viral vector COVID-19 vaccines are no longer used in the US, pharmacists may encounter patients who previously received these vaccines or who were vaccinated internationally. Familiarity with this vaccine technology is important when reviewing vaccination histories, evaluating prior adverse events, and helping patients make informed vaccination decisions.

Inactivated Virus Vaccines

Inactivated virus vaccines contain chemically inactivated SARS-CoV-2 particles that cannot cause infection. Unlike vaccines that target a single viral component, this approach exposes the immune system to multiple viral antigens.⁹ Although these vaccines are not currently available in the United States, they have demonstrated protection against severe COVID-19 outcomes.⁹ Study findings have shown lower neutralizing antibody responses than with mRNA vaccines, making booster doses an important component of maintaining protection over time.⁹

Counseling Patients About Switching Vaccine Platforms

Pharmacists frequently encounter questions about switching between COVID-19 vaccine platforms. These discussions may arise after a previous adverse event, due to concerns about a specific vaccine technology, or because of a patient’s preference for a different vaccine option.

An important consideration when counseling patients is distinguishing between expected reactogenicity and true contraindications. Expected postvaccination reactions, such as fever, fatigue, headache, and injection site soreness, are generally indicative of immune activation and should not be interpreted as a contraindication to future vaccination.² In contrast, severe allergic reactions, including anaphylaxis, may warrant additional evaluation and individualized risk-benefit assessment before subsequent vaccination.²

Additionally, the use of heterologous, or “mix-and-match,” vaccination strategies became increasingly common during the COVID-19 pandemic. Evidence from clinical trials supports the safety and immunogenicity of booster doses administered using a vaccine platform different from that of the primary vaccination series.¹⁰

Conclusion

Although mRNA vaccines have dominated much of the public discussion surrounding COVID-19 vaccination, they represent only one of several technologies developed in response to the pandemic. As COVID-19 vaccination strategies continue to evolve, understanding these approaches offers valuable insight into both the progress achieved to date and the future of vaccine development and disease prevention.

REFERENCES

1. COVID-19 vaccines. CDC. Updated July 30, 2025. Accessed June 23, 2026. https://www.cdc.gov/covid/vaccines/index.html

2. Interim clinical considerations for use of COVID-19 vaccines in the United States. CDC. Updated November 4, 2025. Accessed June 23, 2026. https://www.cdc.gov/covid/hcp/vaccine-considerations/index.html

3. Polack FP, Thomas SJ, Kitchin N, et al; C4591001 Clinical Trial Group. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. N Engl J Med. 2020;383(27):2603-2615. doi:10.1056/NEJMoa2034577

4. Baden LR, El Sahly HM, Essink B, et al; COVE Study Group. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384(5):403-416. doi:10.1056/NEJMoa2035389

5. Oster ME, Shay DK, Su JR, et al. Myocarditis cases reported after mRNA-based COVID-19 vaccination in the US from December 2020 to August 2021. JAMA. 2022;327(4):331-340. doi:10.1001/jama.2021.24110

6. Heath PT, Galiza EP, Baxter DN, et al; 2019nCoV-302 Study Group. Safety and efficacy of NVX-CoV2373 Covid-19 vaccine. N Engl J Med. 2021;385(13):1172-1183. doi:10.1056/NEJMoa2107659

7. Sadoff J, Gray G, Vandebosch A, et al; ENSEMBLE Study Group. Safety and efficacy of single-dose Ad26.COV2.S vaccine against Covid-19. N Engl J Med. 2021;384(23):2187-2201. doi:10.1056/NEJMoa2101544

8. Rosenblum HG, Hadler SC, Moulia D, et al. Use of COVID-19 vaccines after reports of adverse events among adult recipients of Janssen (Johnson & Johnson) and mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna): update from the Advisory Committee on Immunization Practices – United States, July 2021. MMWR Morb Mortal Wkly Rep. 2021;70(32):1094-1099. doi:10.15585/mmwr.mm7032e4

9. Tanriover MD, Doğanay HL, Akova M, et al; CoronaVac Study Group. Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CovonaVac): interim results of a double-blind, randomized, placebo-controlled, phase 3 trial in Turkey. Lancet. 2021;398(10296):213-222. doi:10.1016/S0140-6736(21)01429-X

10. Atmar RL, Lyke KE, Deming ME, et al; DMID 21-0012 Study Group. Homologous and heterologous Covid-19 booster vaccinations. N Engl J Med. 2022;386(11):1046-1057. doi:10.1056/NEJMoa2116414