13-Valent Pneumococcal Conjugate Vaccine (PCV13) in Preterm Versus Term Infants

Abstract

OBJECTIVES: This study evaluated the immune response and safety profile of 13-valent pneumococcal conjugate vaccine (PCV13) in preterm infants compared with term infants.METHODS: This Phase IV, open-label, 2-arm, multicenter, parallel-group study enrolled 200 healthy infants (preterm, n = 100; term, n = 100) aged 42 to 98 days. All subjects received PCV13 at ages 2, 3, 4 (infant series), and 12 (toddler dose [TD]) months, together with routine vaccines (diphtheriatetanus-acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b vaccine and meningococcal group C conjugate vaccine).RESULTS: Most subjects achieved an anticapsular immunoglobulin G (IgG) antibody concentration $0.35 mg/mL for all serotypes: .85% after the infant series (except preterm infants for serotypes 5, 6A, and 6B) and .97% after TD (except for serotype 3). Preterm infants had overall lower IgG geometric mean concentrations compared with term infants; however, geometric mean fold increases after TD were similar for all serotypes. Opsonophagocytic activity results were consistent with IgG results and titers increased after TD in both groups for all serotypes, including serotype 3. PCV13 was generally well tolerated, with similar safety profiles in all preterm subgroups.CONCLUSIONS: Immune responses were lower in preterm infants than in term infants. However, the majority of subjects in both groups achieved both pneumococcal serotype-specific IgG antibody levels after the infant series that exceeded the World Health Organization-established threshold of protection and functional antibody responses. Responses were uniformly higher after TD, reinforcing the importance of a timely booster dose. PCV13 was well tolerated regardless of gestational age.

Schedules for Pneumococcal Vaccination of Preterm Infants: An RCT

“…[4][5][6] The immunogenicity of PCV13 in premature infants receiving a 2-3-4 and 12-month schedule was only recently reported and revealed lower immunoglobulin G (IgG) concentrations for 8 serotypes after both primary and booster doses compared with term infants. 7 This lower immunogenicity is consistent with previous PCV7 studies 8 -10 and is concerning because premature infants are also less likely to benefit from the protective maternal antibodies transferred during late pregnancy.…”

“…4,21 However, compared with previous term (PCV13) and preterm (PCV7) studies, antibody concentrations after primary and booster vaccination are lower overall, resulting in lower seroprotection after primary vaccination. 4,5,8,9,22 Similarly, compared with the recent PCV13 preterm study, 7 lower IgG GMCs and seroprotection rates were seen for all serotypes. These differences may be due to the different laboratory testing methods used for serotype-specific antibody concentrations, but potential biological explanations include interactions with concurrently administered vaccines, the younger gestation of the study cohort, or our broad inclusion criteria encompassing infants with complex medical problems (representative of the preterm population).…”

Immunization of preterm infants

“…However, the majority of preterm infants achieved both pneumococcal serotype-specific IgG antibody levels threshold of protection. 46 In summary, lower vaccine pneumococcal serotypes IgG GMTs were found in preterm infants for primary doses. Accordingly French and Canadian recommendations advocate a regimen of 4 doses (consisting of 3 primary doses with a toddler booster dose) of pneumococcal conjugate vaccines for the routine immunization of preterm infants rather than the 2 C 1 regimen.…”

Advances in Pediatric Pharmacology, Therapeutics, and Toxicology

“…Despite this increased risk for infection, vaccination of preterm infants is often delayed [65]. A clinical trial was conducted to evaluate the immune response and safety profile of the 13-valent pneumococcal conjugate vaccine (PCV13) in preterm compared to term infants on the same vaccination schedule [66]. Two hundred healthy infants (preterm, n=100, term, n=100) between 42 and 98 days postnatal age were enrolled in a phase 4, open label, multicenter parallel-group study.…”

“…The vaccination was tolerated well regardless of gestational age. The investigators concluded that majority of subjects in both groups were able to exceed the World Health Organization threshold of protection and functional antibody response after the infant series [66]. …”