June 2024 ACIP Meeting Update: Influenza, COVID-19, RSV, and Other Vaccines

The Influenza Vaccines Work Group presented updates regarding the H5N1 influenza cases in dairy cattle and the public health response, voted on use recommendations for the 2024 to 2025 influenza season, reviewed safety data from the 2023 to 2024 season, and discussed possible recommendations for off-label use of high dose inactivated or adjuvanted influenza vaccine in solid organ transplant patients who are under the licensed age of 65 years.

Highly pathogenic avian influenza strain (A) H5N1has been detected in birds since 1996 and detectable in various mammals since 2003 to 2004. The 2.3.4.4b clade involved in the current outbreak in cows on more than 100 dairy farms across 12 US states has been circulating since 2020. In the current US highly pathogenic avian influenza outbreak, there have been 3 cases in humans reported after exposure to infected cattle between April 1^st and May 30^th, 2024 (1 case in Texas, 2 cases in Michigan). All patients had conjunctivitis, and 1 patient also had mild cough without fever. All symptoms were mild, and patients recovered without hospitalization. There has not been any known human to human transmission. Current influenza diagnostic assays are able to detect these A(H5N1) viruses, and isolates from detected cases appear to be sensitive to Food and Drug Administration (FDA) approved antiviral drugs, including oseltamivir and baloxavir. Since March 2024, more than 30 000 specimens from public health laboratories have been tested for A(H5N1). Testing will continue as the Centers for Disease Control and Prevention (CDC) has developed a summer influenza surveillance program, which will include subtyping of influenza A positive specimens and monitoring of people with exposure on confirmed farms. The CDC will also continue syndromic case surveillance for individuals with conjunctivitis ± respiratory symptoms and wastewater data monitoring. The CDC’s assessment of overall risk for the general public is currently low; however, risk for those with prolonged exposure to infected animals is considerable. The virus is detectable at high levels in raw milk; however, the virus is destroyed after pasteurization, which is required for all milk sold commercially in the United States. There are 2 recombinant influenza candidate vaccine viruses, developed from H5N1 clade 2.3.4.4b influenza viruses found in other birds and mammals, in the US National Prepandemic Influenza Vaccine Stockpile that have hemagglutinin antigens, which are highly related to the current strain circulating in US dairy cattle.^1,2  Per CDC, these candidate vaccine viruses would be expected to provide good protection via vaccination should the need arise.

As previously reported, all 2024 to 2025 influenza vaccines available in the United States will be trivalent. One update to the strain composition for the 2024 to 2025 vaccine since the last ACIP meeting is a recommendation to use A/Thailand/8/2022 (H3N2) for egg-based vaccines or A/Massachusetts/18/2022 (H3N2) in cell-based vaccines, replacing previously used A/Darwin (H3N2) strains.

The Work Group presented safety surveillance data from the 2023 to 2024 season. Approximately 158 million doses of influenza vaccine were distributed in the United States and no new safety concerns were identified in the FDA’s Vaccine Adverse Event Reporting System (VAERS) or via rapid cycle analysis of the CDC’s Vaccine Safety Datalink (VSD) data as of May 31, 2024.

Finally, the Work Group led a discussion regarding modification to existing influenza vaccine recommendations to include inactivated high-dose (HD-IIV), adjuvanted (aIIV), and recombinant vaccines as options for influenza vaccination of patients who have had solid organ transplant (SOT) who are younger than 65 years of age. Current recommendations are for all individuals ≥6 months to receive an appropriate, age specific influenza vaccine. However, because of diminished vaccine response in the post-transplant setting, the American Society of Transplantation states that high dose or boosted dosing of influenza vaccines may be preferable for those who are receiving immunosuppressive therapies after SOT. High dose and adjuvanted influenza vaccines are currently only licensed for individuals 65 and older, leaving younger patients who have had SOT without a high dose or adjuvanted vaccine option that is available and covered by insurance. The Work Group raised the following policy question for consideration: Should high-dose inactivated, adjuvanted inactivated and/or recombinant influenza vaccines be recommended as an option for influenza vaccination of solid organ transplant recipients who are younger than the approved age indication (65 years for HD-IIV and aIIV, 18 years for recombinant)? The Work Group performed a meta-analysis of 8 studies (1 study only including pediatric patients was excluded) comparing immunogenicity of aIIV3 or HD-IIV versus standard dose inactivated influenza vaccine in patients who have received SOT that were ≥6 months of age. The likelihood of seroconversion was higher with adjuvanted vaccines (1.17–1.64 risk ratio) and high-dose vaccines against Influenza A and B strains; however, there is no direct evidence of clinical benefit against hospitalization or disease. No increased risk in harms was seen with aIIV or HD-IIV.

There is an ongoing study in pediatric patients who have had SOT, so any extension or changes that might include the pediatric population will wait until after those data are available.

The ACIP voted on and unanimously approved the following policy options for influenza vaccines:

1. Routine annual (2024–2025) influenza vaccination is recommended for all persons aged ≥ 6 months without contraindications.

2. HD-IIV3 and aIIV3 influenza vaccines are recommended as acceptable options for influenza vaccination of solid organ transplant recipients aged 18 through 64 years who are receiving immunosuppressive medication regimens, without a preference over other age-appropriate IIV3s or Recombinant Influenza Vaccines (RIV).

The Work Group presented the Evidence to Recommendation framework for universal vaccination with the 2024 to 2025 COVID vaccine for all individuals ≥ 6 months of age. On June 5, 2024, the FDA’s Vaccine and Related Biological Products Advisory Council met to discuss strain selection for the 2024 to 2025 COVID-19 vaccines, and based on the totality of the evidence, the FDA advised manufacturers to develop vaccines targeting the JN.1 lineage severe acute respiratory syndrome coronavirus 2 strains, with preference for KP.2 strain if feasible.

The Work Group provided updated vaccine safety surveillance data for the 2023 to 2024 COVID vaccine from V-safe and VSD. There were 2 safety signals identified for messenger RNA (mRNA) COVID-19 vaccines during the 2023 to 2024 season: Guillain-Barré syndrome (GBS) and ischemic stroke, both in adults 65 years and older. However, it remains unclear whether the increased rate ratio of GBS observed after Pfizer mRNA vaccination and ischemic stroke after any mRNA vaccination in older adults are true risks or not because of possible residual confounding inherent in surveillance studies. The VSD and the FDA both have follow-up studies in progress to further evaluate the risk of stroke, GBS, and other outcomes and are due out later in 2024. No other safety signals were identified for other COVID-19 vaccines or age groups.

There was discussion after presentations of complex economic analyses and the Evidence to Recommendation framework regarding the lack of apparent cost effectiveness of 2024 to 2025 COVID-19 vaccination in children and younger adults and challenges to determining risk-based recommendations. Two-thirds of all COVID-associated hospitalizations are in adults 65 years of age and older, and the greatest economic benefit and impact of vaccination continues to be for this population. However, cost-effectiveness concerns were balanced by data presented that demonstrates that from July 2023 through March 2024, 50% of children who were hospitalized for COVID, and 40% of those who were admitted to the ICU, had no underlying medical conditions. Rates of hospitalization for COVID-19 among children are highest for those <4 years of age and especially high for those <6 months of age who cannot yet receive immunization themselves. Vaccination against COVID-19 has been shown to reduce negative outcomes, including hospitalization, post-COVID conditions, and death in children and adolescents. Furthermore, the number of deaths in children from COVID-19 is still higher than for many other vaccine preventable diseases, including seasonal influenza. The Work Group deliberated between universal and nonuniversal (risk-based or shared decision making) policy options but ultimately concluded that nonuniversal options had significant implementation challenges. Unlike past seasons, it is anticipated that insurance plans will cover the 2024 to 2025 vaccines immediately under the CARES act and that Medicare and Medicaid recipients will have access to the COVID-19 vaccines at no cost, per the Inflation Reduction Act. Vaccines for Children will continue to provide COVID-19 vaccines at no cost to eligible children. It is anticipated that the 2024 to 2025 vaccine will be available to ship between mid-August and late September 2024. On balance, the Work Group favored a universal vaccination approach and recommended the 2024 to 2025 COVID-19 vaccine for all individuals ≥6 months. This language was unanimously approved by the ACIP.

The Meningococcal Vaccines Work Group continues to focus on 2 main topics. The first is the pentavalent pentavalent meningococcal conjugate vaccine (MenABCWY) vaccine being developed by GlaxoSmithKline (GSK), which is currently in stage 2 of 3 clinical trials. A representative from GSK presented a summary of data from the 2 phase 3 safety and immunogenicity studies of GSK’s pentavalent MenABCWY in naïve and MenACWY-primed 10 to 25 year olds, as well as data from an ongoing phase 2 dose timing study examining spacing of 2 doses at 2 vs 4 years apart in 11 to 14 year olds. The safety and reactogenicity profile of MenABCWY was similar to that of serogroup B meningococcal vaccine (MenB)-4c (Bexsero), with comparable rates and severity of adverse events (AEs) in the first 7 days. Immune response to MenABCWY, as measured by human serum bactericidal assay titers, was noninferior for all 4 shared serotypes compared with MenACWY in both naïve and MenACWY-primed participants. Overall, MenABCWY also demonstrated noninferiority in bactericidal effect compared with MenB-4C; however, noninferiority success criteria was not met individually against 2 of the 4 reference strains (PorA and NHBA) at the 6 month dosing interval. These studies also demonstrated persistence of human serum bactericidal assay titers at 24 months and a robust response to a booster dose of MenABCWY booster dose.

Overall, the Work Group felt that GSK’s MenABCWY has a favorable safety profile and mostly favorable immunogenicity results, though 1:1 dosing comparison with MenACWY demonstrated a lower response to serotype A with MenABCWY vaccination and response to 2 reference serotype B strains did not meet noninferiority criteria compared with MenB-4C. The Work Group voiced concerns specifically regarding the drop in protection against serogroup B strains after 2 years and the inferior immune response of MenABCWY to PorA strains, as this represents the full outer membrane vesicle component and has a bearing on the ability of this vaccine to provide cross-protection.

The second topic was potential revision of the adolescent meningococcal vaccine schedule, anticipated to be brought for vote to ACIP in February 2025. The Work Group reviewed the current adolescent meningococcal vaccine schedule and previously proposed schedule options (Table 1). The bulk of the discussion at this meeting was focused on defining risk groups for Meningococcal B vaccination as referenced in schedule option 2 and 3.

Risk group recommendations are based on congregate living settings among adolescents and young adults; however, the Work Group made a clear note that, per ACIP charter, these recommendations do not apply to military or noncivilian populations. Given the time needed to complete the 2 dose meningococcal B series, as well as the duration of protection, the list of high risk congregate living settings proposed by the ACIP includes: college students, boarding schools, congregate foster care, correctional facilities, institutions for persons with developmental disabilities, psychiatric institutions, and religious academies. As previously discussed, the risk of meningococcal B disease for 4-year college students, particularly those in their first year, living on campus or participating in the Greek system, is significantly higher than other individuals in this same age range (18–22 years). However, the Work Group prefers to simplify recommendations to include all college students and, additionally, to include the option for meningococcal B vaccination for any adolescent who desires protection, given that their plans may change in the future, which will affect their congregate living risk.

The proposed language for risk based MenB vaccination is as follows: “Risk group includes adolescents planning to attend college and adolescents in congregate living settings (eg, congregate foster care, boarding school, correctional facility, etc) who are anticipated to remain in this setting long enough to complete the MenB vaccines series. Any adolescent who desires protection may receive MenB vaccine, even if they are unsure of their future plans, which may inform congregate living risk.”

The RSV Maternal/Pediatric Work Group reviewed maternal RSV immunization uptake and safety data from September 2023 through January 2024 and data regarding nirsevimab coverage and efficacy in infants in the first season of use. Additional topics addressed by the Work Group included updates on vaccine supply for the 2024 to 2025 season, additional planned safety monitoring, and clinical considerations for revaccination of women in subsequent pregnancies.

Uptake of the maternal RSV vaccine during the 2023 to 2024 season was low; only 18% of pregnant persons received the vaccine, which somewhat limited early postlicensure studies of efficacy and safety to date. There were slightly higher than expected rates of preterm birth reported in VAERS after maternal RSV immunization, which is included in the package insert as a warning. Data from VSD, however, indicated a rate of preterm birth at 4.1%, which is within the background rate. There is an ongoing 1:1 matched analysis on VSD data, which will provide additional insight. To date, the safety profile of maternal RSV immunization is consistent with prelicensure studies.

Despite some initial challenges to implementation of nirsevimab, including limited supply early in the season, reimbursement issues, complexities of RSV recommendations in the mother-infant dyad, and working within a siloed medical system, approximately 50% of eligible infants received nirsevimab during the 2023 to 2024 RSV season. Real world test negative design effectiveness studies of nirsevimab from October 2024 to March 2024 using data from the New Vaccine Surveillance Network and Virtual severe acute respiratory syndrome coronavirus 2, Influenza, and Other respiratory viruses Network demonstrated 96% (91% to 98%) effectiveness against hospitalization from RSV, 89% against medically attended acute respiratory illness from RSV, and 77% effectiveness against emergency department encounters. Presentation of these data drew applause from the committee. These data remain consistent with effectiveness studies conducted in Europe and reported independently in the medical literature. There are also data from Europe demonstrating a substantial impact in the overall burden of RSV hospitalization after earlier implementation of nirsevimab than was available in the United States. However, it is worth noting that because of the timing and initial limited product availability, the US data may be skewed, as nirsevimab was given preferentially to infants at higher-risk of severe RSV disease in the earliest months after approval. The Work Group reported that there are no concerns for maternal RSV vaccine supply for the 2024 to 2025 season and that although there will be limited supply of nirsevimab in September 2024, it should be broadly available nationwide by October 1st.

Nirsevimab safety will continue to be monitored through MedWatch/FAERS primarily, unless it is administered on the same day as a vaccine, in which case any AEs will be recorded in VAERS. To date, most frequently reported AEs are breakthrough RSV infection and rare serious hypersensitivity reaction, which was added to product labeling as a warning in February 2024.

The Work Group reported that there are no data at this time regarding the need, efficacy, or safety of repeat RSV immunization of women in future pregnancies. Extrapolating data from adult RSV vaccines show that protection decreased over time and was lower in the second RSV season. Phase 1/2 immunogenicity studies demonstrated a lower antibody GMT after a 12-month RSV booster dose than seen with initial vaccination. With other maternal vaccines, such as Tdap and influenza, the benefit to risk ratio generally favors revaccination for benefit to the infant with minimal added risk to the mother. Additional data on antibody levels in previously immunized pregnant people and their infants in subsequent pregnancies will be crucial to informing this risk to benefit ratio of revaccination. Current recommendations for 2024 to 2025 are for a single lifetime dose of RSV vaccine during pregnancy and that nirsevimab should be used for infants born to mothers who received RSV vaccine during a previous pregnancy.

In June 2023, ACIP recommended that adults aged ≥ 60 years may receive RSV vaccination using shared clinical decision-making. The ACIP revised guidance for RSV vaccination in adults at the June 2024 meeting after presentation of robust real world effectiveness data from a large Veterans Affairs study, the relative cost-effectiveness of RSV prevention in older adults (75 years and older) and individuals 60 to 74 years old at risk for severe RSV disease, and discussion of the real-world challenges of “shared decision making”. The new recommendations, approved unanimously by the ACIP, are that all adults 75 years and older should receive a single RSV vaccine, and only adults 60 to 74 years of age at increased risk of severe RSV disease because of a chronic medical condition, including cardiovascular, lung, liver and renal disease, diabetes mellitus with end organ damage, immunocompromising conditions, obesity, neurologic or neuromuscular conditions, frailty, or residence in a nursing home, should receive a single dose of RSV vaccine.

In May 2024, the FDA licensed a third RSV vaccine, mRNA-1345 (Moderna) for use in adults 60 years of age and older. Data from the second RSV season for this vaccine were presented to the ACIP, reflecting a vaccine that was well tolerated, without any safety signals and with comparable efficacy to other licensed adult RSV vaccines at up to 19 months post immunization. The sponsor shared data demonstrating a similar immune response to primary vaccination and safety profile after repeat vaccination at 12 months. GSK also presented immunogenicity and safety data from a 24-month revaccination interval study, which demonstrated a higher neutralizing antibody response than a 12-month revaccination interval. Of note, current recommendations are for a single lifetime dose of RSV vaccine. Representatives from Pfizer shared immunobridging and safety data from ongoing trials of Abrysvo in younger adults (18–59 years), which met noninferiority compared with original study population of 60 years and older. These data are currently under review by the FDA. In October 2023, GSK presented data to ACIP demonstrating that the humoral immune response to a single dose of GSK RSV vaccine in adults 50 to 59 years is noninferior to that in adults ages 60 years and older and these data were subsequently reviewed by the FDA, leading to an expansion of indications for use to include adults 50 to 59 years. The GSK study data were reviewed by the ACIP Work Group, but they felt that they did not have sufficient evidence to provide a recommendation regarding RSV vaccination of adults 50 to 59 years old at risk for severe RSV disease at this time.

CDC and FDA representatives shared real-world RSV vaccine safety data from VAERS and VSD. Analysis of VAERS reports revealed a higher-than-expected number of GBS reports after Pfizer (Abrysvo) RSV vaccination, while noting that VAERS is subject to the limitations of passive surveillance. Subjects who developed GBS were observed in the prelicensure clinical trials for both the Pfizer (Abrysvo) and GSK (Arexvy) RSV vaccines, and GBS is included as an adverse event in the labels of both vaccines. Early data from the VSD also suggest the potential for an increased rate for GBS after the GSK RSV vaccine, but additional analyses are needed to further assess this potential risk. Active monitoring for GBS after RSV vaccines in CDC and FDA population-based surveillance systems is in progress. The FDA is also in the process of performing a postlicensure safety study utilizing 2 designs to analyze data after RSV vaccination with both the RSVPreF (Abrysvo) and RSVPreF3 + AS01 (Arexvy). Using a self-controlled case series analysis, which compared timing of GBS cases in a population of 1.3 million immunized individuals during a defined risk interval (1–42 days post vaccination), the investigators ultimately identified 11 patients diagnosed with GBS after a dose of Arexvy and 17 patients after a dose of Abrysvo. The results of these analyses suggest a possible increased risk of GBS after receipt of RSVPreF vaccine in adults 65 years and older; however, these results are preliminary. Additional verification is needed to further quantify the risk. The FDA is in the final stages of performing chart review validation of these 28 patients diagnosed with GBS after RSV immunization.

The Work Group felt that, overall, from a population perspective based on the latest available data, the estimated benefits of RSV vaccination appear to outweigh the potential risk of GBS in adults 60 years and older. However, there is substantial uncertainty in estimates of both benefit and risk, and the benefit and risk assessment will be updated as additional data become available.

Polyribosylribitol phosphate conjugated with Neisseria meningitidis outer membrane protein Haemophilus influenzae B vaccine (PRP-OMP) (PedvaxHIB) is preferentially recommended for infants of American Indian and Alaska Native (AI/AN) descent as it provides a protective antibody response after the first dose, which is beneficial since Hib meningitis peaks at an earlier age among AI/AN infants. Vaxelis (diphtheria, tetanus, acellular pertussis, inactivated poliovirus, haemophilus influenzae type b, and hepatitis B [DTaP-IPV-Hib-HepB]) does not currently have a preferential recommendation for AI/AN infants because it contains PRP-OMP in a lower amount than PedvaxHIB, and postdose 1 immunogenicity data have not been previously available. The Vaxelis Work Group presented new data from a phase 4, open label, randomized controlled trial conducted in a population of AI/AN infants in Alaska and at 4 sites in the Navajo Nation, which demonstrates noninferior immunogenicity (based on anti-Hib geometric mean concentrations) of Vaxelis compared with PRP-OMP at 30 days post dose 1, as well as a higher proportion of AI/AN infants with an anti-Hib concentration above the putative correlation of short-term protection after the first dose of Vaxelis (75.7% versus 71.2% for PRP-OMP).

This study also demonstrated that the proportion of infants with anti-Hib concentration above the putative correlate of long-term protection at 150 days postdose 1, after completion of the primary vaccination series (3 doses for Vaxelis and 2 doses of PRP-OMP) was higher in the Vaxelis group (83.6%) than in the PedvaxHIB group (71.7%, P < .05). Antibody titers were not collected beyond day 150 postdose 1. In prelicensure clinical trials, the safety profile was consistent with that of licensed comparator vaccines except for a higher rate of fever than with DTaP-IPV/Hib (47% versus 34%). The frequency of serious adverse events was similar between groups, with Vaxelis at 5% and PedvaxHIB at 7%; no serious adverse events were deemed related to the vaccines.

The policy question under discussion by the ACIP was if DTaP-IPV-Hib-HepB (Vaxelis) should be included with PRP-OMP (PedvaxHIB) as an option in the preferential recommendation for American Indian and Alaska Native (AI/AN) infants based on the Hib component. The ACIP unanimously approved the proposed amendment and the Vaccines for Children proposal for addition of Vaxelis as a preferential option in AI/AN infants. The Committee also corrected language that any other Hib conjugate vaccine should be used for booster dose at 12 to 15 months (instead of “may be used” as was previously written).

The ACIP will be restarting an human papillomavirus vaccine (HPV) vaccine work group. The purpose of the work group will be to review new data and consider changes to the number of recommended 9-valent HPV vaccine doses, language regarding starting age for the HPV series, and guidance around shared decision-making recommendations for adults 27 to 45 years. The work group will start meeting in July 2024 and present their discussion on recommended number of doses and starting age at the October 2024 meeting.

At the February 2024 meeting, the ACIP voted to recommend Chikungunya vaccination for all persons aged ≥18 years traveling to a country or territory where there is a chikungunya outbreak and laboratory workers with potential exposure to chikungunya virus. Chikungunya vaccination may be considered for individuals in areas with chikungunya transmission within the past 5 years (but without current outbreak) who are at high risk for severe disease (aged 65 years and older, particularly those with underlying medical conditions), who have at least moderate exposure to mosquitoes, and/or will have at least 6 months of cumulative exposure.

There is currently 1 licensed Chikungunya vaccine (Ixchiq, manufactured by Valneva) in the United States for use as a single dose in persons aged ≥18 years. It is a live vaccine and, as such, is contraindicated in individuals with immunocompromising conditions. A virus-like particle based Chikunguyna vaccine is under development by Bavarian Nordic and the sponsor recently submitted a Biologics License Application to the FDA in mid-June 2024. The proposed indications for this vaccine include use in all individuals 12 years of age and older who are living in US territories with ongoing chikungunya circulation and travelers. No data for this vaccine were presented, but it will be discussed further at the October 2024 meeting.

The Chikungunya Vaccines Work Group reviewed the epidemiology of chikungunya in US territories and freely associated states (Puerto Rico, American Samoa, US Virgin Islands), which was most remarkable for 2 large outbreaks, which occurred in Puerto Rico in 2013 and in the US Virgin Islands in 2014, both resolving within 12 months. In both outbreaks, seroprevalence data indicates that nearly 30% of the population in those areas were infected. Data from the Puerto Rico outbreak also suggests that nearly half of the cases were in children less than 19 years of age, though at least some of this higher prevalence of infection in children may be caused by testing bias. Locally acquired cases in the mainland United States remain rare, with 12 in Florida in 2014 and 1 in Texas in 2015.

Work Group discussion was centered around modeling of cost-effectiveness for outbreak-based versus routine vaccination strategies in US territories. Routine vaccination strategies were shown to be cost saving for all outcomes and were predicted to prevent 90% of associated health outcomes (hospitalization, chronic joint pain and death), whereas the outbreak-based vaccination strategy had mixed results (67% of outcomes averted) but was mostly net positive for costs compared with no vaccination.

In 2020 during the COVID-19 pandemic, invasive pneumococcal disease (IPD) rates reached a historically low level in all age groups. During 2021 to 2023, new pneumococcal conjugate vaccines 15-valent pneumococcal conjugate vaccine (PCV) and 20-valent PCV were recommended for both adults and children. A 21-valent pneumococcal conjugate vaccine (CAPVAXIVETM, Merck) was approved by the FDA for adults aged ≥18 years on June 17, 2024. The current focus of the Work Group is to discuss use of 21-valent PCV (PCV21) in adults. Pediatric pneumococcal vaccine recommendations were not discussed at this ACIP meeting. By proportion of IPD by vaccine-type among adults with a pneumococcal vaccine indication from 2018 to 2022: 20-valent PCV covers 54% to 58% of serotypes causing disease in adults, and PCV1 covers 81% to 85% of serotypes. The Work Group also noted an increase in IPD because of serotype 4 (included in currently available vaccines, but not in PCV21) has been reported in adults experiencing homelessness with a 100 to 300 times higher incidence compared with people who are not experiencing homelessness in the Western United States. Adults in Alaska (especially of Alaska Natives descent) also have an 88-fold increase in serotype 4 IPD incidence from 2011 to 2018 versus 2019 to 2020.

The following adult groups are currently recommended to receive a dose of PCV.

• Adults aged ≥65 years who have not received a PCV

• Adults aged 19 to 64 years with certain underlying conditions or risk factors who have not received a PCV

• Certain adults who have received 13-valent PCV but have not received 20-valent PCV

Noting that adults with risk-based vaccine recommendations have lower vaccine coverage compared with those with age-based recommendation, the Work Group brought the following policy questions to the Committee:

1. Should PCV21 be recommended for US adults aged ≥19 years who currently have a recommendation to receive a PCV (as above)?

2. Should PCV21 be recommended for US adults aged 50 to 64 years who currently do not have a risk-based pneumococcal vaccine indication?

3. Should PCV21 be recommended for US adults aged 19 to 49 years who currently do not have a risk-based pneumococcal vaccine indication?

Ultimately, after review of complex economic analyses and public health impact data, the Work Group agreed that available evidence supports PCV21 use for adults (19 year and older) who are currently recommended to receive a pneumococcal conjugate vaccine. The Work Group could not reach a consensus on whether the age-based recommendation for PCV21 should be lowered from the current ≥65 years to ≥50 years. The majority of Working Group members believed that there was insufficient evidence to support lowering the age-based recommendation for currently recommended vaccines.

The ACIP unanimously approved the following recommendations regarding PCV21 use:

The manufacturer of Dengvaxia, the only licensed dengue vaccine in the United States, is discontinuing production of Dengvaxia because of low demand. The remaining stock of Dengvaxia will continue to be distributed globally and in Puerto Rico through the expiration dates of currently produced vaccine. The last doses will expire at the end of August 2026, so any 3 dose (0, 6, 12 month) immunization series must be started by August 21, 2025. The Work Group presented data from the dengue immunization program in Puerto Rico, which started in September 2022. Since program onset, 264 doses of Dengvaxia have been administered in 145 children ages 9 to 16; 170 children have received a first dose and only 32 have completed the whole 3 dose series. Major barriers to success for this immunization program have been identified as the need for prevaccination serologic testing to confirm past dengue virus infection and multiple medical visits before immunization, complex billing processes, and limited vaccine messaging from local public health institutions.

The Work Group also presented on dengue epidemiology and noted that although the US vaccine option is being discontinued, incident Dengue cases are increasing globally, especially in South and Central America. Over 10 million cases of Dengue have been diagnosed so far this year in the Americas, which is the highest number on record and almost double the number of cases reported in 2023. Puerto Rico has been in a dengue epidemic since the beginning of 2024 and declared a public health emergency in March 2024. After expiration of the remaining Dengvaxia doses, there will not be any licensed vaccine for dengue in the United States, its territories, or freely associated states. Another candidate dengue vaccine, TAK-003 (Takeda), was withdrawn in July 2023. The National Institutes of Health and Merck are actively developing a dengue vaccine, TV003/TV005, which is currently in phase 3 trials in Brazil and may be discussed in the future.

ACIP

Advisory Committee on Immunization Practices

AI/AN

American Indian and Alaska Native

CDC

Centers for Disease Control and Prevention

COVID-19

coronavirus disease 2019

FDA

US Food and Drug Administration

GSK

GlaxoSmithKline

MenABCWY

pentavalent meningococcal conjugate vaccine

MenB

serogroup B meningococcal vaccine

PRP-OMP

polyribosylribitol phosphate conjugated with Neisseria meningitidis outer membrane protein Haemophilus influenzae B vaccine

RSV

respiratory syncytial virus

VAERS

Vaccine Adverse Event Reporting System

VSD

Vaccine Safety Datalink