A recent report published in Morbidity and Mortality Weekly Report provided clinical guidance on Respiratory syncytial virus (RSV) vaccines for adults ≥60 years, with moderate to high efficacy in preventing severe respiratory illness and the potential to reduce morbidity and mortality.
RSV causes seasonal epidemics of respiratory illness in the United States. The coronavirus disease 2019 (COVID-19) pandemic disrupted RSV circulation, but the 2022-23 fall and winter epidemic indicated a gradual return to normal. RSV poses significant health risks to older adults, leading to lower respiratory tract disease, hospitalizations, and deaths. Incidence varies due to testing limitations, but it affects adults aged ≥65, with estimated hospitalizations of 60,000-160,000 and 6,000-10,000 deaths annually.
About the study
The present study revealed that since May 2022, the CDC's Advisory Committee on Immunization Practices (ACIP) RSV Vaccines Adult Work Group has been meeting regularly to assess the safety, immunogenicity, and efficacy of GlaxoSmithKline plc (GSK) and Pfizer RSV vaccines in adults aged ≥60 years.
The authors conducted a systematic review of unpublished and published evidence, including phase 3 and combined phase 1/2 randomized controlled trials for each vaccine. The certainty of the evidence for the results related to each vaccine was evaluated independently using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, which rates evidence certainty from high to very low.
They also assessed safety by looking into inflammatory neurologic events, such as Guillain-Barre syndrome and acute central nervous system inflammation occurring within 42 days of vaccination.
The authors then used the evidence recommendation framework to guide their deliberations on RSV vaccination recommendations, considering public health impact, benefits and risks, acceptability, feasibility, resource use, and equity.
The efficacy of the GSK RSV vaccine in preventing symptomatic, laboratory-confirmed RSV-associated lower respiratory tract disease (LRTD) in adults aged ≥60 years was evaluated through a phase three clinical trial conducted in multiple countries. The trial included 24,973 participants who received one dose of the vaccine or a placebo.
Efficacy analysis covered two RSV seasons for participants from the northern hemisphere and one season for southern hemisphere participants, totaling approximately 15 months per participant.
The vaccine showed 82.6% efficacy during the first season and 56.1% during the second season in preventing RSV-associated LRTD. The study demonstrated a 74.5% efficacy in preventing LRTD and a 77.5% efficacy in preventing clinically attended RSV-associated LRTD over two seasons.
Regarding safety, data from two clinical trials were considered, including a phase 3 trial and a phase ½ trial. Severe reactogenicity events occurred in 3.8% of vaccinated participants compared to 0.9% in the control group. The frequency of serious adverse events was similar between the intervention and control groups. However, there were more reports of atrial fibrillation as an unsolicited event within 30 days after vaccination in the intervention group.
Additionally, three inflammatory neurologic events were reported, including one case of Guillain-Barre syndrome and two cases of acute disseminated encephalomyelitis (ADEM) in participants who received the vaccine. The ADEM cases occurred in conjunction with the standard dose of the seasonal influenza vaccine, leading to uncertainty in the diagnoses. One of the ADEM cases was fatal, and its diagnosis was later revised to hypoglycemia and dementia.
It's important to note that the safety data mentioned for the GSK vaccine came from different trials and that some events were rare. The efficacy and safety information presented here was based on the evidence available up to March 2023.
The Pfizer RSV vaccine’s efficacy data were obtained from an ongoing phase 3 clinical trial involving 36,862 immunocompetent individuals aged ≥60 years in multiple countries. The trial analyzed data collected from August 2021 to January 2023, covering one complete RSV season for both southern and northern hemisphere individuals and a partial second season for individuals of Northern hemisphere.
The vaccine showed 88.9% efficacy during the first season and 78.6% during the partial second season in preventing RSV-associated LRTD. The overall efficacy over two seasons was 84.4% in preventing RSV-associated LRTD and 81.0% in preventing medically attended RSV-associated LRTD.
Regarding safety, the Pfizer vaccine data came from two clinical trials, including a phase 3 trial and a phase ½ trial. Severe reactogenicity events occurred in 1.0% of vaccinated participants compared to 0.7% in the control group.
The frequency of serious adverse events was similar between the intervention and control groups. Within 30 days after vaccination, a greater number of participants in the intervention group reported atrial fibrillation.
Additionally, three inflammatory neurologic events were reported in participants who received the vaccine, including Guillain-Barre syndrome, Miller-Fisher syndrome, and undifferentiated motor-sensory axonal polyneuropathy.
On June 21, 2023, the ACIP's recommendation allowed adults aged ≥60 years to receive a dose of RSV vaccine through shared clinical decision-making. This means that vaccination decisions should be based on discussions between healthcare providers and patients, considering the patient's risk for severe RSV-associated disease, individual characteristics, values, and preferences, as well as the characteristics of the vaccine.
High-risk individuals for severe RSV disease include those with chronic medical conditions, compromised immunity, diabetes, neurologic or neuromuscular conditions, kidney and liver disorders, frailty, advanced age, and those residing in long-term care facilities. Although clinical trials had limited representation of certain populations, vaccination is still recommended for them using shared clinical decision-making.
RSV vaccination should ideally occur before the RSV season but given the disrupted seasonality due to the COVID-19 pandemic, the vaccine should be offered to eligible adults as early as it becomes available.
It is acceptable to administer RSV vaccines concurrently with other adult vaccines during the same visit, but the available data on immunogenicity and reactogenicity for various vaccine combinations are limited.
Providers should assess the patient's vaccination history, risk for vaccine-preventable diseases, reactogenicity profiles, and patient preferences before coadministering RSV vaccines with other vaccines.
Precautions and contraindications are similar to other vaccines, including delaying vaccination during moderate to severe acute illness and not administering the vaccine to those with a history of severe allergic reactions to any vaccine component. Post-licensure monitoring will provide more guidance on coadministered RSV vaccines with other vaccines.
The GSK and Pfizer RSV vaccines showed moderate to high efficacy in preventing symptomatic RSV-associated LRTD in adults aged ≥60 years over two RSV seasons.
Although efficacy against hospitalization and death was not well-established, preventing LRTD and medically attended cases suggest potential benefits in reducing RSV-related morbidity. The vaccines were generally well-tolerated, but a few cases of inflammatory neurologic events were reported post-vaccination.