The Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) discussed vaccinations for COVID-19, influenza, respiratory syncytial virus (RSV), pneumococcal infections, and other infectious diseases and made some related recommendations during their first 2024 meeting, held February 28 to 29.

COVID-19 Vaccine Recommendations

The ACIP now recommends that persons 65 years of age and older should receive an additional dose of the updated (2023-2024) COVID-19 vaccine.¹ The additional dose must be administered at least 4 months following the previous dose of the updated vaccine.

Adults aged 65 years and older have expressed a high level of concern about COVID-19, with 68.4% of individuals indicating they would definitely receive another vaccine dose should it become available.² The effectiveness of an additional dose of COVID-19 vaccine is demonstrated by past recommendations.

The need for the recommended 4-month COVID-19 booster vaccine for those age 65 and older is supported by both hospitalization data and scientific reasoning. An estimated 67% of COVID-19 hospitalizations were among patients age 65 years and older between October 2023 and January 2024, according to ACIP current respiratory season calculations made using data from COVID-NET, a population-based hospitalization surveillance program.³ Moreover, hospitalizations were 5 times higher for those age 65 years and older vs those aged 50 to 64 years.

The need for booster protection is also indicated by data showing that older adults may not be able to generate robust, long-lasting neutralizing antibody responses or good memory cytotoxic T-cells as there are fewer naive T-cells that respond to new pathogens.²

Vaccine formulations for the next COVID-19 season are already underway.²

Notably, members of the ACIP expressed concern that offering booster vaccinations for those age 65 and older at 4-month intervals could create vaccine fatigue as well as confusion for providers, given that immunocompromised patients may receive a booster dose following a 2-month interval.

In their June 2024 meeting, the ACIP plans to propose revised time frames for COVID-19 vaccine development and vaccination that will allow health care providers ample time to prepare for the COVID-19 viral season.

RSV Vaccine Developments

An ACIP work group on RSV vaccination in older adults presented its recommendation that providers and patients “consider timing of the RSV vaccination as part of shared clinical decision-making discussions,” noting that for most older adults, RSV vaccination is most beneficial when received in late summer or early fall, before the start of RSV season.⁴

Although shared decision-making between patient and provider is currently recommended for determining whether or not an adult patient should receive the RSV vaccine, this recommendation may be replaced by a universal recommendation that adults above a certain age receive the RSV vaccine, and a risk-based recommendation that adults over age 50 years receive the vaccine, according to the work group report, “RSV Vaccination in Older Adults: Work Group Interpretations.”⁴

The ACIP also expressed its intention to discuss the potential approval of the GSK RSV vaccine, AREXVY, for those aged 50 to 59 at “increased risk of RSV disease” at their June meeting.  AREXVY is currently approved for use in adults aged 60 and above.⁴

In anticipation of RSV-related actions set for June, the ACIP reviewed RSV vaccine data related to the Moderna mRNA vaccine.^4,5 The committee also discussed concerns over the potential connection between currently approved RSV vaccines and an increased incidence of Guillain-Barré Syndrome (GBS).

Moderna mRNA RSV Vaccine

Moderna has been conducting a clinical trial for their mRNA-based RSV vaccine for adults age 60 years and older (ClinicalTrials.gov Identifier: NCT05127434), which works by encoding the RSV fusion (F) glycoprotein.⁵ According to an ACIP report on trial findings that was presented at the February meeting, the vaccine has been generally well tolerated, efficacious through a median 8.6 months of follow-up, and presented no safety concerns (including no concern over GBS).

The trial enrolled a total of 26,550 healthy adults age 60 years and older, including those with chronic, stable health conditions. The primary endpoint was vaccine efficacy in preventing the first episode of RSV lower respiratory tract disease (LRTD) between 14 days and 12 months post-vaccination. The secondary endpoint was vaccine efficacy in preventing the first episode of RSV acute respiratory disease (ARD) and first hospitalization between 14 days and 12 months.

Trial investigators found that vaccine efficacy for RSV-LRTD with 2 or more symptoms reached 83.7%, whereas efficacy for RSV-LRTD with 3 or more symptoms was calculated as 82.4%.⁵ The efficacy threshold for RSV-ARD was set at 68.4%. Vaccine efficacy met lower bounds of confidence interval criteria to exceed 20%.

RSV Vaccines and GBS

For the February ACIP meeting, CDC’s Immunization Safety Office and the US Food and Drug Administration (FDA) shared preliminary data from multiple surveillance systems on the risk for GBS after RSV vaccination.⁴

An elevated but rare risk for GBS was observed following administration of the GSK’s AREXY and Pfizer’s ABRYSVO vaccines for RSV.  According to the work group report on RSV Vaccination in Older Adults, current surveillance data “support a potential increased risk for GBS after RSV vaccination among adults aged ≥60 years.”⁴

The report went on to note that “there is currently insufficient evidence to confirm whether RSV vaccination is associated with increased risk for GBS in older adults, or to estimate the magnitude of any increase in GBS risk after RSV vaccination.”⁴

Currently, clinical trials are underway evaluating the safety of these vaccines, examining the association between RSV vaccines and the incidence of GBS. More conclusive evidence of potential risks following RSV vaccination will be available following RSV monitoring using self-controlled case series designs.

Influenza Immunization in Children With Asthma

The ACIP also assessed evidence evaluating the safety of the live attenuated influenza vaccine (LAIV4) in children with asthma.⁶ The evidence indicated that LAIV4 may be a suitable option for children age 5 years and older with asthma.

Evidence presented included a study assessing whether LAIV4 is noninferior to IIV4. The study included 151 patients between the ages of 5 and 7 years with persistent asthma who were randomly assigned to 2 groups: one receiving LAIV4 FluMist and the other receiving IIV4 Fluzone. On days 15 and 43, the 2 groups were evaluated for symptoms following vaccination. The study investigators compared the proportion of patients using LAIV4 vs IIV4 who experienced an asthma exacerbation during the 42 days following vaccination.

Study findings showed that in the 14 days following vaccination, 3 exacerbations were reported among those receiving LAIV4 vs 4 exacerbations among those receiving IIV4 (3.9% vs. 5.7%, P =.74). In the 42-day symptom assessment, 8 asthma exacerbations were documented among those receiving LAIV4 and 10 among those receiving IIV4 (10.8% vs. 14.7%, p = 0.74). The upper bound for noninferiority was set at 10% with a difference in proportion of 3.9 (CI: 90%: -0.15, 0.07).⁶ Researchers rejected the null hypothesis and proved LAIV4 noninferiority to IIV4.

Limitations of the study include the enrollment of fewer participants than intended, setting the power at 79% and the enrollment of patients within 2 separate flu seasons, which may have led to slightly different products.

Further discussion of the suitability of LAIV4 for children age 5 years and older with asthma is anticipated at future ACIP meetings.

Pneumococcal Vaccination: PCV21 Considerations

The ACIP also discussed incorporating a recently developed pneumococcal vaccine, V116, a 21-valent pneumococcal conjugate vaccine (PCV21), into its roster of recommended pneumococcal vaccines. Toward that end, the committee reviewed phase 3 clinical trial results for V116 (ClinicalTrials.gov Identifier: NCT05425732).

The ACIP reported that the following policy questions are being actively considered by its work group:⁷

1. Should PCV21 be recommended for US adults aged 19 and older who currently have a recommendation to receive a PCV?
2. Should PCV21 be recommended for US adults aged 50 to 64 years who do not have risk-based indication for the pneumococcal vaccine?
3. Should PCV21 be recommended for US adults aged 19 to 49 years who do not have risk-based indication for the pneumococcal vaccine?

About 30% to 40% of adult invasive pneumococcal disease (IPD) cases are caused by serotypes that are not contained in currently available pneumococcal vaccines.⁸ The PCV21 vaccine contains most of these serotypes and provides broader coverage. In a phase 3, randomized, double-blind, active comparator-controlled clinical study of the V116 PCV21 vaccine, V116 was concluded to be superior to PCV20 for 10 out of the 11 of its unique strains.

The work group concluded that pneumococcal disease is of public health importance to adults currently recommended for PCV vaccination. While it may be appropriate to expand vaccination to patients between the ages of 50 to 64, committee members concluded that epidemiology does not support expanding vaccination to younger adults without indication.

At its June meeting, the ACIP plans to consider official draft policies on PCV21 use in US adults.⁷