Vaccines in development: What we can look forward to in preventing infectious diseases

Publication
Article
Contemporary PEDS JournalNovember 2021
Volume 38
Issue 11

What we can look forward to in preventing infectious diseases.

More than 2600 vaccines are in development world- wide for several infectious diseases.1,2 When they are licensed and become available, some of the vaccines would have a significant effect on various diseases in the United States (Table).

Table

Table

Pneumococcal disease vaccines

Vaccine-related and nonvaccine Streptococcus pneumoniae serotypes continue to cause a significant amount of morbidity and mortality in infants and children. Two increased valency pneumococcal conjugate vaccines (PCV) are in the process of completing phase 3 clinical trials in the pediatric population. PCV15 (Merck) is expected to be licensed by the end of 2021; PCV20 (Pfizer), by the second quarter of 2022. Both vaccines protect against some of the additional serotypes that have emerged as significant causes of pneumococcal infections in infants and children.

Meningococcal disease vaccines

The currently recommended meningococcal vaccine schedule is a source of confusion for patients and health care providers. A universal recommendation states that all pre- teens and adolescents should receive the first dose of meningococcal quadrivalent conjugate vaccine (ACW135Y) at age 11 to 12 years, followed by a booster dose at 16 years. However, meningococcal serogroup B vaccines have a shared clinical decision recommendation so that only some adolescents may receive the vaccine. Two pentavalent meningococcal conjugate vaccines that contain meningococcal serotypes AB- CW135Y are completing phase 2 (Pfizer) and phase 3 (GlaxoSmithKline) clinical trials. These vaccines combine the quadrivalent ACW135Y meningococcal and the meningococcal serogroup B vaccines into a single vaccine. This vaccine will 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.

Respiratory syncytial virus vaccine

Respiratory syncytial virus (RSV) usually causes mild, coldlike symptoms. However, this common respiratory virus can lead to severe bronchiolitis or pneumonia, especially in young infants, older adults, and people with serious cardiopulmonary or underlying immunocompromising conditions. Each year, more than 57,000 children and 177,000 older adults are hospitalized with RSV infections.3 Two RSV vaccines are currently in phase 1 (Moderna) and phase 3 (Pfizer) clinical trials. The Pfizer vaccine is being tested in adults 60 years or older, healthy adults aged 18 to 50 years, and pregnant women aged 18 to 49 years and their infants. Moderna’s vaccine, which was created using mRNA technology, is being examined for tolerability and its ability to create antibodies to protect against RSV in individuals ranging from children to older adults. The licensing of an effective RSV vaccine could have a major effect on reducing the number of hospitalizations caused by this virus.

Cytomegalovirus vaccine

An estimated 1 out of every 200 babies is born with a congenital cytomegalovirus (CMV) infection; of those infected babies, 1 out of 5 babies will have long-term health problems. 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. The risk of transmission following nonprimary infection is much lower (3%). 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. Congenital CMV infection is the leading nongenetic cause of sensorineural hearing loss in children in the United States, resulting in an estimated 21% of all hearing loss at birth and 25% of childhood hearing loss by 4 years of age.4 Moderna is getting set to start a phase 3 study to evaluate the efficacy of its mRNA vaccine against primary CMV infection in a population that includes women of childbearing age, with the goal of a vaccine that can be administered to pregnant women.

Human metapneumovirus and parainfluenza 3 vaccines

Human metapneumovirus (HMPV) and human parainfluenza virus (HPIV)-3 are common respiratory viruses that can cause upper and lower respiratory tract disease in people of all ages, especially young children, older adults, and immunocompromised people, in whom disease may be severe. Although HPIV-1 and HPIV-2 both cause croup, HPIV-3 is more often associated with 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 show that the different doses of the vaccine were immunogenic and well tolerated. A phase 1b trial is planned to look at the vaccine’s immunogenicity in seropositive toddlers who have previously been exposed to these viruses.

Group B Streptococcus vaccine

Group B streptococcus (GBS) 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 the elderly. Pfizer has completed a phase 1 and 2 dose-escalation trial to evaluate the safety and immunogenicity of a hexavalent conjugate GBS vac- cine in nonpregnant adults aged 18 to 49 years. The findings showed that the vaccine was well tolerated in healthy adults and elicited robust immune responses for all dose levels and formulations tested, which persisted for 6 months after vaccination. The next step will be to perform a trial in pregnant women.5

More than a dozen vaccines are in development and show promise for infections commonly seen in the pediatric population. Soon, we hope to use these new tools in our offices and at our hospitals.

References

1. WHO vaccine pipeline tracker. World Health Organization. Accessed Sept 5, 2021. https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines

2. Health products in the pipeline from discovery to market launch for all diseases. World Health Organization. Updated September 2021. Accessed September 5, 2021. 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. Respiratory syncytial virus infection (RSV). Centers for Disease Control and Prevention. Accessed October 1, 2021. https://www.cdc.gov/rsv/research/us-surveillance.html

4. Fowler KB. Congenital cytomegalovirus infection: audiologic outcome. Clin Infect Dis. 2013;57(suppl 4):S182-S184. doi:10.1093/cid/cit609

5. Absalon J, Segall N, Block SL, et al. Safety and immunogenicity of a novel hexavalent group B streptococcus conjugate vaccine in healthy, non-pregnant adults: a phase 1/2, randomised, placebo-controlled, observer-blinded, dose-escalation trial. Lancet Infect Dis. 2021;21(2):263-274. doi:10.1016/S1473-3099(20)30478-3

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