Fall 2023 ACIP Update on Meningococcal, RSV, COVID-19, and Other Pediatric Vaccines

On September 12, the ACIP had a special session to discuss use of the updated monovalent XBB COVID-19 messenger RNA (mRNA) vaccines during the 2023–2024 respiratory illness season, after the September 11, 2023, FDA authorization of the updated 2023–2024 COVID-19 mRNA vaccines containing the monovalent XBB 1.5 component and a revocation of authorization for previous Pfizer-BioNTech and Moderna bivalent mRNA and ancestral monovalent Novavax COVID-19 vaccines.² The COVID-19 work group presented current epidemiology, noting that 23% to 34% of children and adolescents who were hospitalized for COVID-19 since January 2023 and 50% of those children who have died of COVID-19 since January 2022 did not have any underlying medical conditions. COVID-19 remains the leading cause of vaccine-preventable death in children in the United States.

The committee also heard safety and immunogenicity data presentations from representatives from Moderna for their new XBB1.5 monovalent 2023–2024 formula COVID-19 vaccines, as well as nonclinical (mouse model and nonhuman primate model) immunogenicity from Pfizer and Novavax for their updated XBB vaccines. All 3 vaccines demonstrated robust levels of neutralizing antibodies against XBB, as well as other emerging severe acute respiratory syndrome coronavirus 2 variants. The Moderna 2023–2024 formula was well tolerated by human volunteers, with a similar reactogenicity profile to previous Moderna COVID-19 vaccines.

At the close of the September session, the ACIP voted to recommend that all individuals 6 months of age and older receive at least 1 dose of updated 2023–2024 COVID-19 vaccine, either as part of an age-appropriate primary series (2–3 doses) for children 6 months through 4 years of age or individuals that are moderately or severely immunocompromised; or as a single dose, for those who were previously up to date on COVID-19 vaccination or are 5 years of age and older and immunocompetent (12 years and older for Novavax). In the discussion surrounding the vote, it was noted that the risk of severe complications from COVID-19 is not the same across all age groups, and that, in the future, there may come a time where the benefit of COVID-19 vaccines is no longer significant enough to justify routine immunization in younger and low-risk age groups. However, the committee acknowledged that, at this time, there is evidence of benefit, including at least some protection against postCOVID-19 conditions, in all age groups. It also remains unclear at this time what the timing of any future updates to COVID-19 vaccines will look like, because severe acute respiratory syndrome coronavirus 2 is still circulating year-round without clear seasonality.

The October 2023 COVID-19 session opened with brief review of the current epidemiology, with emphasis that ο XBB lineages are still dominant in the United States, and that there are still ∼1200 deaths per week from COVID-19. The remainder of the session focused on the challenges of vaccine implementation after the transition from federal support of COVID-19 vaccines to the commercial market. Although all COVID-19 vaccines are now part of the commercial market, the committee reviewed access options, noting that all persons in the United States can still access a COVID-19 vaccine at no cost. No-cost options include traditional insurance, Medicare/Medicaid, the Vaccines for Children (VFC) Program, and the Bridge Access Program for adults 18 and older who are underinsured or uninsured. Despite efforts to facilitate no-cost access, a review of the National Immunization Survey found that only 7.1% of adults and 2.1% of children reported receiving an updated COVID-19 vaccine since they became available in September 2023. Although 25% to 30% of respondents stated they would definitely get the updated COVID-19 vaccine in the near future, about 35% stated that they and/or their children probably or definitely won’t get vaccinated. There was extensive discussion surrounding the very low uptake of COVID-19 vaccines in young children. The ACIP chair and the 2 American Academy of Pediatrics liaisons (D.W.K. and S.T.O.) all spoke up about the difference in what these survey data show (with ∼65% potentially willing to vaccinate their children) and what vaccination data show, pointing out that much of the difference has to do with barriers to delivery, such as the high cost of stocking the product and the uncertainty around reimbursement. There was further committee discussion on potential methods to improve communication regarding COVID-19 vaccines, which included streamlining recommendations, education of the public and of providers, and additional mass communication strategies. The committee reviewed recommendations made at the previous September 12 meeting regarding the 2023–2024 COVID-19 vaccine and clarified that, although recommendations for primary COVID-19 immunizations for children <5 years old still include a preference that all doses should be from the same manufacturer (Moderna versus Pfizer), there are circumstances where a vaccine from a different manufacturer would be permitted to promote ease of access or prevent a delay in vaccination. Essentially, if the same vaccine is not available at the time of the clinic visit, the previous dose was unknown, or they would not otherwise receive their COVID-19 vaccine, an age-appropriate vaccine from a different manufacturer can be given.

RSV continues to be the leading cause of hospitalization in US infants. Most infants are infected in the first year of life and nearly all by age 2 years. Prematurity and other chronic diseases increase risk for RSV-associated hospitalization, but most hospitalizations are in healthy, term infants. There are 2 new products for prevention of RSV disease in infants that have recently been discussed by ACIP: A monoclonal antibody and a maternal vaccine.

On August 3, 2023, nirsevimab, a long-acting monoclonal antibody against RSV, was recommended for use for prevention of RSV lower respiratory tract disease in all infants aged ≥8 months born during or entering their first RSV season and for infants/children aged 8 to 19 months who are increased risk for severe RSV disease entering their second RSV season.

Later in August 2023, Pfizer’s new RSV prefusion F (PreF) vaccine, a bivalent recombinant stabilized PreF protein subunit vaccine which had previously been licensed for adults aged 60 years and older, was approved for the indication for use in individuals who are pregnant for protection of their infants from 0 through 6 months of age against RSV lower respiratory tract disease. On September 22, 2023, the ACIP held a special meeting to vote on recommendations for use of the RSV PreF vaccine in individuals who are pregnant.³ The recommended schedule for the RSV PreF vaccine (120 ug antigen) in pregnancy is for a single intramuscular dose, given between 32 and 36 weeks’ gestation. Of note, this is a narrower gestational age range than was studied in the clinical trials (down to 24 weeks); this modification was made upon licensure by the FDA to decrease potential risk of complication of extreme preterm birth and is because of concerns regarding a numerical imbalance in the number of preterm births in pregnant RSV PreF recipients compared with placebo in the clinical trials. At this meeting, RSV work group members presented the proposed safety surveillance studies for maternal RSV immunization through the Vaccine Safety Datalink and Vaccine Adverse Event Reporting System/V-Safe programs, cost-effectiveness analyses of maternal immunization for prevention of RSV and updated EtR, and clinical considerations for use of Pfizer’s RSV PreF and nirsevimab.

The RSV work group proposed seasonal administration of this vaccine, which would be September through January in most of the United States during a typical (prepandemic) year, but may vary in other jurisdictions such as Alaska and subtropical regions of the United States. The work group felt that local public health officials should have the flexibility to determine the RSV season for their location. Nirsevimab’s effectiveness has been studied for up to 5 months after administration, but the duration of protection against RSV disease for longer than 5 months is not clear. For this reason, seasonal vaccination, as opposed to year-round, maximizes both the benefit to the neonatal population and cost-effectiveness.

ACIP members voted on the policy question, “Should Pfizer RSV PreF vaccine be recommended for individuals who are pregnant, to be given during 32 and 36 weeks’ gestation to prevent RSV lower respiratory tract infection in infants?” This language and recommendation was approved with 11 in favor and 1 against. After the main recommendation vote, the VFC resolution for coverage of RSV PreF in individuals 18 years of age and younger who are pregnant was also approved.

There was extensive discussion at the meeting regarding the challenge presented by having 2 products recommended for prevention of RSV disease in infants, 1 during pregnancy and 1 for newborns. Cost effectiveness analyses demonstrated that, for most infants, use of both products was an incredibly inefficient use of resources, and there was consensus both within the work group and at the ACIP meeting that, for most infants, if the maternal vaccine was given during pregnancy, the infant should not receive nirsevimab. These issues will be addressed in clinical considerations for the products with the following guidance:

For the maternal RSV PreF vaccine: Either maternal vaccination or use of nirsevimab in the infant is recommended to prevent RSV lower respiratory tract infection, but administration of both products is not needed for most infants.

Health care providers of individuals who are pregnant should provide information on both products and consider patient preferences, as well as individual gestational timing in relation to RSV season, when determining whether to vaccinate the pregnant patient or to not vaccinate and rely on administration of nirsevimab to the infant after birth.

For nirsevimab: Nirsevimab is recommended for infants aged <8 months born during or entering their first RSV season if the mother did not receive RSV vaccine or unknown if mother received RSV vaccine and if the mother was vaccinated but infant was born <14 days after vaccination. Nirsevimab is not needed for most infants born ≥14 days after maternal vaccination. Nirsevimab can be considered in addition to maternal vaccination in rare circumstances when, per the clinical judgment of the health care provider, the potential incremental benefit of administration is warranted. This includes infants born to pregnant people who may not mount an adequate immune response to vaccination (eg, people with immunocompromising conditions) or who have conditions associated with reduced transplacental antibody transfer (eg, people living with HIV infection); infants who have undergone cardiopulmonary bypass, leading to loss of maternal antibodies; and infants with substantial increased risk for severe RSV disease (eg, hemodynamically significant congenital heart disease, intensive care admission, and requiring oxygen at discharge).

After comments from the ACIP committee at the June 2023 meeting regarding potential changes to the general meningococcal vaccine schedule, the meningococcal work group has decided to examine additional data regarding the epidemiology of meningococcal disease after the onset of the COVID-19 pandemic, cost effectiveness analyses, and other data; discussions will be ongoing, with any potential change to the overall meningococcal vaccine schedule not occurring until early 2025. The focus of the October 2023 meeting was on providing recommendations for use of Pfizer’s pentavalent meningococcal conjugate vaccine (MenABCWY), which was licensed by the FDA on October 20, 2023, for use as a 2-dose series, at 0 and 6 months, in individuals 10 through 25 years of age. The Pfizer MenABCWY is composed of 2 preexisting Pfizer vaccines: Bivalent factor-H binding protein meningococcal serogroup B (Trumenba) and meningococcal quadrivalent conjugate (MenACWY) tetanus toxoid (Nimenrix, not licensed in the United States, but used extensively in Europe).

There was discussion among committee members regarding a desire to wait to make recommendations for pentavalent vaccine usage until the overall meningococcal vaccine schedule could be reevaluated; however, newly FDA approved products are generally discussed by ACIP soon after FDA licensure. The committee ultimately decided that a recommendation on the pentavalent vaccine was needed today and that recommendations for use would be revisited in the future when new data are available.

The meningococcal work group members presented 3 policy questions regarding recommendations for use of the MenABCWY vaccine to the committee:

1. Should Pfizer’s pentavalent MenABCWY vaccine be included as an option for MenACWY/serogroup B meningococcal vaccine (MenB) in people currently recommended to receive both vaccines (ie, individuals 16 years and older)?

   • This would result in a recommendation for a dose of quadrivalent at age 11 to 12 years, a dose of pentavalent at age 16 years and a dose of MenB at age 16.5 years and older, also known as the Quadrivalent-Pentavalent-MenB approach.

2. Should the pentavalent vaccine be included as an option for people currently recommended to receive MenACWY only (ie, 11–12-year-olds)?

   • a. Pentavalent doses given at age 11 to 12 years and age 16 years and then no additional meningococcal vaccines given (Pentavalent-Pentavalent-Nothing approach).

3. Should the pentavalent vaccine be included as an option for people currently recommended to receive MenB only (ie, 16–23-year-olds based on shared decision-making)?

   • a. Quadrivalent given at age 11 to 12 years, pentavalent given at age 16 years, and again as a second dose 6 months later (Quadrivalent-Pentavalent-Pentavalent approach).

To further explore these policy questions, 2 different cost effectiveness analysis models, developed by Pfizer and the CDC, were reviewed for each policy question compared with standard of care. There were 2 major updates to these models from the analyses presented in June 2023:

1. a reduced projected vaccine cost of the Pfizer pentavalent vaccine ($210 per dose [private]/$157 [public]) on the FDA-approved 2-dose schedule, with a higher cost ($250 private/$187 public) if a single pentavalent dose schedule was recommended; and

2. updated pentavalent vaccine effectiveness (VE) data.

Both models demonstrated a cost-saving outcome for policy questions 1 and 3, but not with policy question 2. Although there are no available head-to-head immunogenicity trials for the various potential dosing strategies considered above, on the basis of efficacy of the individual meningococcal vaccine products, each of the strategies considered would likely prevent a similar number of annual invasive meningococcal cases and deaths. All of the above regimens would also prevent slightly more meningococcal cases and related deaths than the current standard of care. An updated EtR analysis of the 3 policy questions was also presented.

Overall, the work group favored policy option 1 (QPB) or possibly option 3 (as QPB or QPP), depending on how shared clinical decision-making continues to be incorporated for MenB vaccines. After extensive discussion and additional revisions by committee members, the proposed language developed for a vote was as follows:

“Pfizer’s MenABCWY vaccine may be used when both MenACWY and MenB are indicated at the same visit.*

• * 1. Healthy individuals aged 16 to 23 years (routine schedule) when shared clinical decision-making favors administration of MenB vaccination; and

• 2. Individuals aged 10 years and older at increased risk of meningococcal disease (eg, because of persistent complement deficiencies, complement inhibitor use, functional or anatomic asplenia) due for both vaccines.”

The work group noted that this proposal applies to healthy individuals (routine schedule) and those at increased risk for meningococcal disease. A robust discussion of ACIP members followed this proposal with concerns raised over both the real-world feasibility of practices stocking 3 different meningococcal vaccines, as well as the high relative cost of each strategy compared with the low pre COVID-19 pandemic (2019) incidence of 0.11 cases per 100 000 population.⁴ 

The ACIP approved the proposed language for MenABCWY use recommendations by a vote of 10 in favor, 4 against, and 0 abstentions.

The VFC resolution for MenABCWY was adjusted to reflect the ACIP-approved language above and was unanimously approved by the committee.

Although mpox transmission peaked in the summer of 2022, daily case rates never reached 0, and currently average 2 to 4 cases per day in the United States with rates increasing in other parts of the world. Currently, the ACIP recommendation for the use of the JYNNEOS vaccine in adults aged 18 years and older applies during outbreaks, without a recommendation for routine use. Because of continued cases in at-risk populations, the committee proposed and subsequently unanimously approved an interim recommendation for routine immunization with the 2-dose JYNNEOS series for people aged 18 years and older that are at risk for mpox. This interim recommendation for routine immunization of at-risk adults will be reassessed in 2 to 3 years, with consideration given to evolving epidemiology, potential commercialization of JYNNEOS, and updated cost-effectiveness analysis.

Safety and effectiveness data were also reviewed with updated VE of 2 doses at 83% with no new or unexpected safety concerns (including myopericarditis) identified. Recommendations for persons <18 years of age were clarified without significant change, reiterating that adolescents at risk for mpox based on the above factors may receive the JYNNEOS vaccine series. Results from the ongoing National Institutes of Health trial for use of JYNNEOS in 12- to 18-year-olds may be available in late 2024 to inform dosing in that population. The last mpox item was unanimous approval to include the vaccine in the VFC program. Because VFC covers children through age 18 and the ACIP recommendation is for 18 years and older, this will only apply to 18-year-olds once the vaccine is commercially available.

In recent meetings, the dengue work group has presented on Takeda’s TAK-003 candidate dengue vaccine, which has been under review by the FDA since November 2022. On July 11, Takeda voluntarily withdrew their biologics license application for dengue vaccine candidate TAK-003 from FDA review. The company’s rationale is that the FDA had requested additional data not collected in the original trial. Given this, the dengue work group will be paused until TAK-003 is resubmitted to FDA or a new vaccine is submitted for approval.

The work group reviewed current epidemiology of invasive pneumococcal disease from the CDC Active Bacterial Core Surveillance Database, which increased in 2022 in both the adult and pediatric population. Up to 40% of recent invasive pneumococcal disease cases were caused by non–20-valent pneumococcal conjugate vaccine strains, enforcing continued need for additional pneumococcal vaccine development. There are several new pneumococcal vaccines in late stages of clinical development. Merck is developing a 21-valent pneumococcal conjugate vaccine (V116) from Merck, which is currently in phase 3 studies in adults and for which the submission of a biologics license application to the FDA is anticipated in late 2023/early 2024. There are 2 24-valent pneumococcal conjugate vaccines from GSK and Vaxcyte currently in phase 1 and 2 trials (including at least 1 trial in infants).

There were 3 presentations on the safety and effectiveness of newer influenza vaccination in pregnant women and their infants, and an update regarding influenza B surveillance and likely changes to influenza vaccine composition in future years.

A postlicensure safety study conducted by Kaiser Permanente Northern California, which compared pregnancy and infant outcomes after use of recombinant (Flublok) versus standard (Fluarix/Flulaval) quadrivalent influenza vaccines in >44 000 pregnant persons reported low rates of pregnancy complications and adverse birth outcomes overall, and did not demonstrate any significant difference in pregnancy complications or birth/infant outcomes between vaccines.

A representative from CSL Seqirus, the manufacturer of Flucelvax, an inactivated, cell-based quadrivalent influenza vaccine (ccIIV4), presented pregnancy and infant outcomes from 665 women and their offspring who received the vaccine during pregnancy. Rates of stillbirth, spontaneous abortion, preterm birth, low birth weight, and major congenital malformations were all low and below the US background rates, raising no safety concerns.

A representative from the CDC New Vaccine Surveillance Network Influenza Division presented real-world effectiveness data from a case-control, test-negative design study, which aimed to evaluate whether maternal influenza vaccination during pregnancy reduced influenza associated hospitalization and emergency department visits in infants <6 months of age. The study spanned 4 influenza seasons (2016–2020) and 7 pediatric medical centers, and factored in infant age at outcome, study site, and seasonal timing of maternal vaccination. Of the 3764 infants included in the study, 223 tested positive for influenza (cases), 42% (n = 94) who were born to vaccinated mothers, and 3541 tested negative for influenza, 54% (n = 1913) who were born to vaccinated mothers. Overall, maternal immunization was effective in reducing influenza illness in infants (VE 34%, 95% confidence interval 12–50) and hospitalization because of influenza (VE 39%, 95% confidence interval 12–58). Effectiveness was greatest in infants <3 months of age and in those born to mothers who were vaccinated during their third trimester, which is consistent with current vaccine recommendations. There were some potential confounders in the study, including lower rates of breastfeeding and higher rates of preterm birth and underlying medical conditions in infants of unvaccinated mothers, though these differences did not meet statistical significance.

Influenza surveillance systems, such as the World Health Organization’s Global Influenza Surveillance and Response System, actively monitor influenza-positive samples and strain identification at 152 national influenza centers and laboratories across the world. Over the past 3 years (since March 2020), global influenza surveillance has not detected any B/Yamagata lineage influenza viruses, which is a current component of the quadrivalent influenza vaccines licensed in the United States. Given this trend, and the potential risk of reintroduction of B/Yamagata via the use of quadrivalent live-influenza vaccines, the World Health Organization has recommended that influenza vaccines for the 2024 southern hemisphere influenza season no longer contain B/Yamagata, only B/Austria (which is from the B/Victoria lineage).⁵ This will likely result in a similar recommendation for the 2024–2025 northern hemisphere influenza season, as well as a renewed interest and utility for previously licensed trivalent influenza vaccines (which were not licensed for the current 2023 influenza season). The current 2023–2024 influenza vaccines in the United States do contain antigens for both B/Austria (B/Victoria lineage) and B/Phuket (B/Yamagata lineage), in addition to H1N1 and H3N2 influenza A viruses. Any patients in the United States who test positive for influenza B in the 2023–2024 influenza season will have assays performed via local public health laboratories to determine lineage, and any B/Yamagata detections will be sent to the CDC for confirmation.

The work group plans to publish the approved 2024 immunization schedules earlier than in past years (November for Web/digital dissemination and Morbidity and Mortality Weekly Report release in January 2024). Pending release of the new schedule, they will now include an addendum with all approved changes to the immunization schedule, available at https://www.cdc.gov/vaccines/schedules/hcp/imz/child-adolescent.html#addendum-child. Major additions to the pediatric schedule, as discussed in this document, include the addition of MenABCWY, mpox for high-risk individuals, RSV vaccine (Abrysvo) for pregnant people, RSV monoclonal antibody (nirsevimab) for infants, 2023–2024 COVID-19 vaccine and 15-valent pneumococcal conjugate vaccine/20-valent pneumococcal conjugate vaccine. The notes for the influenza section were also updated to indicate that persons with egg allergy, regardless of severity, can receive any licensed influenza vaccine.

ACIP

Advisory Committee on Immunization Practices

CDC

Centers for Disease Control and Prevention

COVID-19

coronavirus disease 2019

EtR

Evidence to Recommendations

FDA

US Food and Drug Administration

MenABCWY

pentavalent meningococcal conjugate vaccine

MenACWY

meningococcal quadrivalent conjugate vaccine

MenB

serogroup B meningococcal vaccine

mRNA

messenger RNA

PreF

prefusion F

RSV

respiratory syncytial virus

VE

vaccine effectiveness

VFC

Vaccines for Children