Updated COVID-19 Vaccines Effectively Protect Against Symptomatic Infection

New research confirms that updated mRNA COVID-19 vaccines provide strong protection against symptomatic infection across multiple platforms, according to a study in Vaccine.¹ As these trials’ results are some of the first real-world reports of COVID-19 vaccine efficacy, researchers concluded that protein-based and mRNA vaccines may have a promising future in infectious disease prophylaxis.

“In the midst of the greatest public health emergency since the flu pandemic of 1918, scientists took a new vaccine technology, based on mRNA, and ran with it,” an article from Weill Cornell Medicine read.² “However, throughout the pandemic and to this day, vaccine skeptics have had an outsize impact, sowing doubt and fear related to the very technology that was saving lives and protecting all of us against the worst effects of the coronavirus.”

The BEEHIVE (NCT06065176) clinical trial, a single-site study conducted in Utah, evaluated the real-world safety and vaccine effectiveness of the 2023–2024 COVID-19 vaccine formula (targeting the XBB.1.5 lineage) in adults who had previously received at least 2 mRNA vaccine doses.¹

READ MORE: The Effects of COVID-19 Influencing the Development of Vaccines

The results showed an adjusted vaccine effectiveness of 43.6% against rapid-antigen test-confirmed symptomatic SARS-CoV-2 infection.

Real-World Clinical Findings

This trial is particularly notable because it evaluated vaccine performance in a heterologous booster context, directly comparing the real-world performance of the widely used mRNA platforms with a recombinant protein-based alternative in primed individuals. Both vaccine platforms were found to be highly effective and well-tolerated, with no serious vaccine-related adverse events, myocarditis, pericarditis, or hospitalizations reported during the study.¹

Although the study was underpowered due to recruitment challenges and was unable to statistically establish the noninferiority of the protein vaccine compared with the mRNA vaccine, the overall data demonstrated robust protection across both modalities.

For pharmacists, this trial provides crucial evidence that protein subunit options, which do not require freezing and can be stored at standard refrigeration temperatures, offer a practical, highly effective alternative to simplify clinical storage logistics and expand population coverage.

Formula Evolution, Sustained Protection

As the SARS-CoV-2 virus continues to mutate, clinical evidence demonstrates that updating vaccine formulas is necessary to maintain meaningful protection.^2,3

A large observational study of US veterans evaluating the 2024–2025 KP.2-targeting COVID-19 vaccine showed that vaccination concurrently administered with the seasonal flu shot remained highly protective against severe clinical outcomes. Over 6 months of follow-up, the updated vaccine showed 29.3% effectiveness against emergency department visits, 39.2% against hospitalizations, and 64% against COVID-19–associated deaths.³

This protection was observed across all age groups and among individuals with major chronic conditions, despite a modest waning of protection over 6 months.

Looking ahead to future seasons, the FDA’s Vaccines and Related Biological Products Advisory Committee recommended that the 2026-2027 vaccine formula include the monovalent JN.1-lineage XFG variant as the preferred virus strain to match newly circulating variants.⁴

This continuous evolution of the vaccine formula highlights why maintaining current booster regimens is critical, particularly because protection against mild-to-moderate infection naturally wanes over time.^1-3

The Frontline Role of the Community Pharmacist

For pharmacists, being the primary touchpoint for immunizations is a public health responsibility. During the pandemic, the Federal Retail Pharmacy Program (FRPP) administered approximately 314.9 million COVID-19 vaccine doses, accounting for 48.9% of all doses administered in the US.⁵

With 90% of Americans living within 5 miles of a pharmacy, community pharmacies provided an unparalleled and equitable avenue for vaccination, successfully reaching diverse populations and extending care to both urban and rural areas. The legacy of this program continues, with CDC data showing that 71.5% of vaccinated adults now receive their updated boosters at community pharmacies.

As the most accessible health care providers, pharmacists are uniquely positioned to navigate patient concerns, distinguish vaccine myths from clinical reality, and explain the immunological differences between platforms. For instance, patients may inquire about the inflammatory profile of mRNA vaccines, which is largely driven by the lipid nanoparticle carrier, or raise concerns about how repeated antigenic stimulation might impact long-term immunity.^2,5,6

By utilizing peer-reviewed evidence to explain how both platforms stimulate protective immunity and how protein-based alternatives provide reliable protection with a low reactogenicity profile, pharmacists can help rebuild public trust, counter vaccine skepticism, and ensure their communities remain protected.^1,6

“Building on existing evidence, our findings offer valuable insights for policy development, particularly in shaping updated COVID-19 vaccine recommendations,” concluded the authors of the current study.¹ “There is a critical opportunity for future research to explore the comparative effectiveness of vaccines, ultimately supporting greater choice and accessibility for the public.”

READ MORE: COVID-19 Resource Center

REFERENCES

1. Yoon SK, Phillips AL, Battan-Wraith S, et al. Real-world effectiveness and safety of protein-based and mRNA COVID-19 vaccines (BEEHIVE trial). Vaccine. 2026;88:128954. doi:10.1016/j.vaccine.2026.128954

2. Here’s what we know: the impact of mRNA vaccines. Weill Cornell Medicine. September 25, 2025. Accessed August 18, 2026. https://weillcornell.org/news/here%E2%80%99s-what-we-know-the-impact-of-mrna-vaccines

3. Cai M, Xie Y, Al-Aly Z. Association of 2024–2025 Covid-19 vaccine with Covid-19 outcomes in U.S. Veterans. NEJM. 2025;393(16):1612-1623. doi:10.1056/nejmoa2510226

4. COVID-19 vaccines (2026-2027 formula) for use in the United States beginning in fall 2026. CDC. May 29, 2026. Accessed August 18, 2026. https://www.fda.gov/vaccines-blood-biologics/industry-biologics/covid-19-vaccines-2026-2027-formula-use-united-states-beginning-fall-2026

5. El Kalach R, Jones-Jack NH, Grabenstein JD, et al. Pharmacists’ answer to the COVID-19 pandemic: contribution of the Federal Retail Pharmacy Program to COVID-19 vaccination across sociodemographic characteristics-United States. J Am Pharm Assoc (2003). 2025 Jan-Feb;65(1):102305. doi: 10.1016/j.japh.2024.102305

6. Igyártó BZ, Qin Z. The mRNA-LNP vaccines - the good, the bad and the ugly? Front Immunol. 2024 Feb 8;15:1336906. doi: 10.3389/fimmu.2024.1336906