Respiratory Diseases Roundup

New Influenza and RSV Research Highlights Vaccine Effectiveness and Hospitalization Prevention

Edited by:
Ashton L. Stahl

Key Highlights

  • An investigational mRNA influenza vaccine demonstrated 26.6% relative efficacy compared with licensed standard-dose vaccines in adults aged 50 years or older.

  • Providing oseltamivir to at least 70% of eligible nursing home residents within 2 days of outbreak detection was associated with fewer hospitalizations at 14 days.

  • Maternal RSVpreF vaccination was 67.6% effective against RSV-associated acute respiratory illness hospitalization in infants aged 90 days or younger.

  • Adjuvanted RSVpreF3 vaccination was associated with 75.6% effectiveness against RSV-related hospitalization in US adults aged 60 years or older.

mRNA Flu Vaccine Outperforms Standard Dose¹

In a phase 3, double-blind, active-controlled trial, researchers evaluated the investigational trivalent mRNA-1010 seasonal influenza vaccine in adults aged 50 years or older. The trial, published in The New England Journal of Medicine, randomly assigned 40,703 participants to receive mRNA-1010, containing 12.5 μg of mRNA for each of 3 World Health Organization–recommended influenza strains, or a licensed standard-dose influenza vaccine. The primary efficacy outcome was reverse transcription–polymerase chain reaction–confirmed, protocol-defined influenza-like illness caused by influenza A or B beginning 14 days after vaccination through the end of the influenza season. Investigators sequentially tested noninferiority, superiority, and a higher prespecified level of superiority. Median follow-up was 181 days.

Influenza-like illness meeting the primary outcome occurred in 411 of 20,179 mRNA-1010 recipients (2%) and 557 of 20,124 standard-dose vaccine recipients (2.8%). Relative vaccine efficacy was 26.6% (95% CI, 16.7%-35.4%), meeting all 3 prespecified efficacy criteria. Solicited reactions were more common with mRNA-1010, including injection-site pain (65.8% vs 29.8%), fatigue (45.1% vs 20.3%), headache (37.8% vs 18.0%), and myalgia (35.4% vs 11.6%); most were mild to moderate and transient. Serious adverse events occurred in 2.2% and 1.9% of participants, respectively, with 3 and 2 events considered vaccine-related by investigators.

The researchers concluded that mRNA-1010 was superior to licensed standard-dose vaccines for preventing confirmed influenza-like illness in this population, although the investigational vaccine produced greater reactogenicity.

Prompt Prophylaxis Lowers Hospitalization Risk²

Researchers used a retrospective cohort design to examine whether rapid, widespread oseltamivir chemoprophylaxis during nursing home influenza outbreaks was associated with lower mortality and hospitalization. The investigators emulated a sequential cluster-randomized target trial using electronic health record data from 12 US nursing home corporations from September 2018 through May 2022.

The analysis, published in JAMA Internal Medicine, included 404 outbreaks at 318 nursing homes, representing 35,086 resident-trial observations among 29,683 residents. The median resident age was 78 years; 60% were women, 81% were White, and 76% had received influenza vaccination. The intensive strategy provided oseltamivir to at least 70% of eligible residents within 2 days of outbreak detection; the comparison strategy provided prophylaxis to fewer than 70%. Outcomes were all-cause death and hospitalization within 14 and 30 days.

At 14 days, the weighted hospitalization risk was 3.58% with intensive prophylaxis and 4.54% with non-intensive prophylaxis, corresponding to a risk difference of −0.96 percentage points (95% CI, −1.78 to −0.19) and a risk ratio of 0.79 (95% CI, 0.64-0.96). At 30 days, hospitalization risks were 6.26% and 7.33%, respectively; the risk ratio was 0.85 (95% CI, 0.64-1.05), with a less precise estimate that included no difference. Intensive prophylaxis was not associated with lower mortality at either time point.

The authors concluded that administering oseltamivir to at least 70% of eligible residents within 2 days of outbreak detection was associated with a lower 14-day hospitalization risk. They noted that rapid, widespread prophylaxis, including residents in units without identified cases, may help inform nursing home outbreak-management practices.

Maternal RSV Vaccine Protects Young Infants³

In a retrospective, test-negative case-control study published in JAMA Network Open, researchers assessed maternal bivalent respiratory syncytial virus prefusion F (RSVpreF) vaccination during the first 2 post-licensure RSV seasons. Conducted within a single health system in western Pennsylvania, the study included infants aged 90 days or younger who were hospitalized with acute respiratory illness and tested for RSV by nucleic acid amplification or rapid antigen testing during the 2023-2024 and 2024-2025 seasons. Maternal vaccination was defined as RSVpreF administration from 32 weeks 0 days through 36 weeks 6 days of gestation and at least 14 days before delivery. The primary outcome was RSV-associated acute respiratory illness requiring hospitalization; RSV-associated lower respiratory tract disease hospitalization was secondary. Vaccine effectiveness was estimated using multivariable logistic regression.

Among 274 infants, 83 tested positive for RSV and 191 served as RSV-negative controls. The mean age at admission was 29.5 days, and 52.2% were male. Eleven RSV-positive infants (13.3%) and 71 controls (37.2%) were born to vaccinated individuals. Estimated vaccine effectiveness was 67.6% (95% CI, 33.2%-85.4%) against RSV-associated acute respiratory illness hospitalization and 69.0% (95% CI, 25.5%-88.0%) against RSV-associated lower respiratory tract disease hospitalization through 90 days of age. Among infants aged 30 days or younger, effectiveness against RSV-associated acute respiratory illness hospitalization was 74.2% (95% CI, 25.4%-93.0%).

The authors concluded that maternal RSVpreF vaccination was associated with protection against RSV hospitalization in young infants. They noted that larger, more diverse studies across additional RSV seasons are needed to refine effectiveness estimates, evaluate protection beyond early infancy, and assess durability.

RSVPreF3 Reduces Hospitalization in Older Adults⁴

In a retrospective cohort study published online in CHEST, researchers evaluated the real-world effectiveness of the adjuvanted RSVPreF3 vaccine against respiratory syncytial virus–related hospitalization in US adults aged 60 years or older. Investigators used Optum Research Database administrative claims from August 2022 through May 2024 and identified vaccinated and unvaccinated adults from August 2023 through May 2024. Each vaccinated participant was matched with 4 unvaccinated participants by age, sex, insurance type, and state of residence. Twelve months of continuous enrollment were required to measure baseline characteristics. Propensity score weighting addressed additional baseline differences, and Cox proportional hazards models estimated vaccine effectiveness beginning 14 days after the index date. RSV-related hospitalization was identified using diagnosis codes.

The analysis included 520,440 vaccinated adults and 2,081,760 matched unvaccinated adults. Participants had a mean age of 74.3 years, 56.9% were female, and median follow-up was 5 months, with a maximum of 10 months. Estimated vaccine effectiveness against RSV-related hospitalization was 75.6% (95% CI, 69.8%-80.2%). Effectiveness remained evident in prespecified high-risk groups, including adults with chronic pulmonary disease (72.5%; 95% CI, 64.3%-78.8%), cardiovascular disease (72.2%; 95% CI, 64.1%-78.4%), diabetes (82.3%; 95% CI, 74.2%-87.9%), or immunocompromising conditions (71.4%; 95% CI, 57.0%-81.1%).

The researchers concluded that adjuvanted RSVPreF3 vaccination was associated with lower RSV-related hospitalization risk among older adults, including those with clinically important comorbidities.

References

  1. Leroux-Roels I, Huang G, Ferguson M, et al; Fluent Trial Investigators. Efficacy and safety of an mRNA seasonal influenza vaccine in adults. N Engl J Med. 2026;394(18):1803-1813. doi:10.1056/NEJMoa2516491.

  2. Silva JBB, Hsieh HT, Howe CJ, Gravenstein S, Reich LA, Zullo AR. Prompt and intensive antiviral chemoprophylaxis in nursing home influenza outbreaks. JAMA Intern Med. 2026;186(6):714-722. doi:10.1001/jamainternmed.2026.0401.

  3. Rick AM, Deese J, Kerr JE, et al. Maternal respiratory syncytial virus prefusion F vaccination and acute respiratory illness in infants. JAMA Netw Open. 2026;9(6):e2616773. doi:10.1001/jamanetworkopen.2026.16773.

  4. Singer D, Steffens A, La E, et al. Real-world effectiveness of adjuvanted RSVPreF3 vaccination in the prevention of RSV-related hospitalization among US adults aged 60 years or older. Chest. Published online July 16, 2026.