What's new in pediatric vaccines

Vaccines are one of the greatest public health achievements of the 20th and 21st centuries, and the global pipeline for future vaccines looks bright. Worldwide, there are currently over 4300 vaccines in development for a host of infectious diseases.^1,2 These vaccines would have a significant impact on various diseases here in the United States when they are licensed and available which is incredibly exciting, as the implementation and use of these vaccines could potentially markedly decrease the morbidity and mortality associated with these diseases.

Respiratory syncytial virus (RSV) vaccine

As noted in an article by Lori Handy, MD, (“The changing landscape of RSV prevention,“) 2 RSV vaccine products were recently licensed to protect infants, pregnant women, and older adults against severe RSV disease. The bivalent RSV prefusion F vaccine (RSVpreF; Pfizer) is licensed for use in adults 60 years or older³ and in pregnant women at 32 to 36 weeks gestation; it should be administered before the start of RSV season.⁴ For infants, the long-acting monoclonal antibody nirsevimab-alip (Beyfortus; AstraZeneca, Sanofi), is licensed for the prevention of RSV lower respiratory tract disease in infants. It is recommended for all infants younger than 8 months, who are entering their first RSV season.⁵ Data from the infant trials demonstrated an efficacy of 80.6% in preventing hospitalization, and 90% in preventing intensive care unit admission.⁵ These RSV vaccines will have a major impact on decreasing the number of hospitalizations caused by the virus.⁵

Pneumococcal disease vaccines

Vaccine-related and nonvaccine Streptococcus pneumoniae serotypes continue to cause a significant amount of morbidity and mortality in infants and children. Recently, 2 increased-valency pneumococcal conjugate vaccines (PCVs) were licensed for use in the pediatric population, PCV15 (Vaneuvance; Merck) and PCV20 (Prevnar; Pfizer).⁶ These vaccines provide protection against many of the additional pneumococcal serotypes that have emerged as significant causes of pneumococcal infections in infants and children. There are several recombinant pneumococcal protein/polysaccharide hybrid vaccines in development that use different pneumococcal proteins as carriers of the pneumococcal capsular polysaccharides. According to results from phase a 1/2 clinical trial (NCT03803202), a 24-valent PCV given to healthy adults aged 18 to 64 years and older adults aged 65 to 85 years was well tolerated and produced very robust immune responses across all age groups that were superior for all PPSV23 serotypes and several PCV13 serotypes. This type of vaccine may offer significantly broader protection over the existing pneumococcal vaccines.⁷

Meningococcal disease vaccines

The current recommended meningococcal vaccine schedules remain a source of confusion for both patients and health care providers, given that it is universally recommended for children aged 11 to 12 years to receive the quadrivalent meningococcal conjugate vaccine (MenACWY) with a booster dose at 16 years of age, whereas the meningococcal B vaccine (MenB) is only recommended for adolescents and young adults (aged 16 to 23 years) and for those that are 10 years or older with underlying conditions or who are taking medications that place them at increased risk for meningococcal disease.⁸ There are 3 pentavalent meningococcal conjugate vaccines that contain meningococcal serotypes ABCW135Y that are completing phase 3 clinical trials (Sanofi-Pasteur)⁸ or have completed clinical trials (Pfizer,⁹ GSK¹⁰). These vaccines are the quadrivalent ACWY meningococcal vaccine and the meningococcal serogroup B vaccine combined into a single vaccine.⁹ The Pfizer pentavalent vaccine was approved by the FDA and is being evaluated by the CDC’s Advisory Committee on Immunization Practices.¹⁰ Once this vaccine is available, it may simplify administering the recommended meningococcal vaccines to preteens and adolescents, improve vaccination rates, and provide protection against the most common meningococcal serotypes that cause disease.

Cytomegalovirus vaccine

Cytomegalovirus (CMV) continues to cause a significant amount of disease with an estimated 1 of every 200 babies being born with a congenital CMV infection. A sobering finding is that 1 out of every 5 babies born with a congenital CMV infection will have long-term health problems, including vision problems, sensorineural hearing loss, muscle weakness, developmental delay, and intellectual disability.¹¹ A pregnant woman can pass CMV to her fetus following primary infection, reinfection with a different CMV strain, or reactivation of a previous infection during pregnancy. The risk of transmission for primary infection is 30% to 40% in the first and second trimesters and 40% to 70% in the third trimester.¹¹ The risk of transmission following nonprimary infection is much lower (3%).¹¹ Approximately 40% to 60% of symptomatic infants with congenital CMV infection have permanent sequelae. In addition, 10% to 15% of infants with asymptomatic CMV infection will have some type of permanent impairment.¹¹ Congenital CMV infection is the leading nongenetic cause of sensorineural hearing loss in children in the United States. It is estimated that 21% of all hearing loss at birth is due to congenital CMV infection and that by 4 years of age, 25% of childhood hearing loss is due to congenital CMV infection.¹¹ Moderna has an ongoing phase 3 clinical trial (NCT05085366) to evaluate the efficacy of its mRNA CMV vaccine against primary CMV infection in a population that includes women of childbearing age.¹² The ultimate goal is for this vaccine to be administered to pregnant women in order to prevent CMV infection of their infants.

Human metapneumovirus and parainfluenza 3 vaccines

Human metapneumovirus (HMPV) and human parainfluenza virus (HPIV) are common respiratory viruses that can cause upper and lower respiratory tract disease in individuals of all ages, especially among young children, older adults, and immunocompromised people in whom the disease may be severe. Although HPIV-1 and HPIV-2 both cause croup, HPIV-3 is more often associated with more severe diseases such as bronchiolitis, bronchitis, and pneumonia. Moderna has developed a combination HMPV and HPIV-3 vaccine that is nearing the end of its phase 1 clinical trials in adults. Data from the trials (NCT04144348, NCT03392389) showed that the different doses of the vaccine were immunogenic and well tolerated.¹³ There is a phase 1b trial that is planned to look at the immunogenicity and safety of the vaccine in seropositive toddlers who have previously been exposed to these viruses. Moderna has also developed a combination RSV and HMPV vaccine that is in phase 1 clinical trial (NCT05743881) in the pediatric population.¹³

Group B streptococcus vaccine

Group B streptococcus is a common bacterium that is often carried in the intestines or lower genital tract. It may cause serious invasive disease (eg, bacteremia, pneumonia, meningitis, osteoarticular infections) in newborns and young infants, anyone with an immunocompromising condition, and elderly individuals. Pfizer has an ongoing phase 2 clinical trial (NCT03765073) of a multivalent conjugate Group B streptococcus vaccine in pregnant women aged 18 to 49 years.¹⁴ Preliminary data from the trial showed that the vaccine was well tolerated and generated robust maternal antibody responses that were transmitted to their infants.¹⁴

There are a number of promising vaccines that have recently been licensed or that are in development for infections very commonly seen in the pediatric population. In the near future, we will hopefully be able to use these vaccines to protect our patients against a growing number of common infections and prevent the complications and hospitalizations associated with them.

Click here for more from the October 2023 issue of Contemporary Pediatrics®.

References:

1. World Health Organization. WHO vaccine pipeline tracker. Accessed Sept 7, 2023. https://www.who.int/teams/regulation-prequalification/eul/eul-vaccines/tracking-the-new-vaccine-pipeline

2. World Health Organization. Health products in the pipeline from discovery to market launch for all diseases. Updated July 2023. Accessed Sept 7, 2023. https://www.who.int/observatories/global-observatory-on-health-research-and-development/monitoring/health-products-in-the-pipeline-from-discovery-to-market-launch-for-all-diseases

3. U.S. FDA approves Abrysvo, Pfizer’s vaccine for the prevention of respiratory syncytial virus (RSV) in older adults. News release. Pfizer. May 31, 2023. Accessed September 11, 2023. https://www.pfizer.com/news/press-release/press-release-detail/us-fda-approves-abrysvotm-pfizers-vaccine-prevention

4. U.S. FDA approves Abrysvo, Pfizer’s vaccine for the prevention of respiratory syncytial virus (RSV) in infants through active immunization of pregnant individuals 32-36 weeks of gestational age. News release. Pfizer. August 21, 2023. Accessed September 11, 2023. https://www.pfizer.com/news/press-release/press-release-detail/us-fda-approves-abrysvotm-pfizers-vaccine-prevention-0

5. Grading of recommendations, assessment, development, and evaluation (GRADE): nirsevimab, season 1. CDC. August 24, 2023. Accessed September 11, 2023. https://www.cdc.gov/vaccines/acip/recs/grade/nirsevimab-season1-rsv-infants-children.html

6. U.S. FDA approves Prevnar 20, Pfizer’s 20-valent pneumococcal conjugate vaccine for infants and children. Pfizer. April 27, 2023. Accessed Sept 7, 2023. https://www.pfizer.com/news/press-release/press-release-detail/us-fda-approves-prevnar-20r-pfizers-20-valent-pneumococcal

7. Chichili GR, Smulders R, Santos V, et al. Phase 1/2 study of a novel 24-valent pneumococcal vaccine in healthy adults aged 18 to 64 years and in older adults 65 to 85 years. Vaccine. 2022;40(31):4190-4198. doi:10.1016/j.vaccine.2022.05.079

8. Meningococcal vaccination for preteens and teens: information for parents. CDC. October 12, 2021. Accessed September 11, 2023. https://www.cdc.gov/vaccines/vpd/mening/public/adolescent-vaccine.html

9. Huang L, Snedecor SJ, Balmer P, Srivastava A. Potential public health impact of a Neisseria meningitidis A, B, C, W, and Y pentavalent vaccine in the United States. Postgrad Med. 2022;134(4):341-348. doi:10.1080/00325481.2021.1876478

10. Advisory Committee on Immunization Practices recommends Prevnar20 (20-valent pneumococcal conjugate vaccine) in infants and children. News release. Pfizer. June 22, 2023. Accessed September 11, 2023. https://www.pfizer.com/news/announcements/advisory-committee-immunization-practices-recommends-prevnar-20r-20-valent

11. Babies born with congenital CMV. CDC. May 27, 2022. Accessed September 11, 2023. https://www.cdc.gov/cmv/congenital-infection.html

12. Moderna announces first participant dosed in phase 3 pivotal registration study of its mRNA cytomegalovirus (CMV) vaccine. News release. Moderna. October 26, 2021. Accessed September 11, 2023. https://investors.modernatx.com/news/news-details/2021/Moderna-Announces-First-Participant-Dosed-in-Phase-3-Pivotal-Registration-Study-of-Its-mRNA-Cytomegalovirus-CMV-Vaccine/default.aspx

13. August A, Shaw CA, Lee H. Safety and immunogenicity of an mRNA-based human metapneumovirus and parainfluenza virus type 3 combined vaccine in healthy adults. Open Forum Infect Dis. 2022;9(7):ofac206. doi:10.1093/ofid/ofac206

14. Madhi SA, Anderson AS, Absalon J, et al. Potential for maternally administered vaccine for infant group B streptococcus. N Engl J Med. 2023;389(3):215-227. doi:10.1056/NEJMoa2116045