Elsevier

Vaccine

Volume 38, Issue 27, 2 June 2020, Pages 4236-4245
Vaccine

Review
Persistence of bactericidal antibodies following primary and booster MenACWY-TT vaccination of toddlers: A review of clinical studies

https://doi.org/10.1016/j.vaccine.2020.02.048Get rights and content

Abstract

The long-term persistence of antibody responses following primary vaccination with quadrivalent conjugate vaccines targeting meningococcal serogroups A, C, W, and Y (MenACWY) and the duration of protection following a booster dose have not been fully elucidated, particularly in children who received primary dosing as toddlers. This review summarizes the findings of one phase 3 and three phase 2 open-label, randomized clinical studies that assessed the long-term antibody persistence of MenACWY conjugated to tetanus toxoid as a carrier protein (MenACWY-TT) in toddlers. Following primary vaccination, antibody responses persisted for approximately 2–3 years and then decreased up to 5 years after vaccination. Geometric mean titers remained elevated for all serogroups up to 5 years after primary vaccination. In children who received a booster dose of MenACWY-TT at 4–5 years after primary dosing as toddlers, antibody responses were documented in >99% of subjects across all serogroups, with minimal decreases in antibody persistence from 2–6 years after booster vaccination. The persistence of meningococcal serogroup C (MenC) antibody responses was similar between MenACWY-TT and MenC vaccine recipients after primary and booster dosing. Together, these findings indicate that antibody responses to primary MenACWY-TT vaccination persist for 2–3 years. Additionally, these findings indicate that in subjects who receive primary MenACWY-TT vaccination as toddlers, the antibody response to booster MenACWY-TT vaccination lasts for up to 6 years and suggest that immune memory is afforded at least into early adolescence, which is an age group at increased risk of invasive meningococcal disease.

Introduction

Invasive meningococcal disease (IMD) is associated with considerable morbidity and mortality, with infants and young children particularly at risk because of their immature immune system [1], [2]. IMD has severe consequences for children; septic shock and its complications, including hearing loss, seizure, amputation, and skin scarring, are more common in children younger than 5 years (21%) than in adults (15%) [3]. Additionally, the predicted case fatality rate in children 1–5 years of age is 7.3%–9.0% [4]. Unfortunately, the diagnosis of IMD in infants and young children may be difficult because they often present with nonspecific signs such as irritability and lethargy [2], [3]. Therefore, prevention of IMD through vaccination is critical in this vulnerable population.

Vaccines are available to protect against the 5 most common meningococcal serogroups (ie, A, B, C, W, and Y) [5], including several quadrivalent conjugate vaccines targeting IMD caused by meningococcal serogroups A, C, W, and Y (MenACWY) that are currently licensed in toddlers [6], [7], [8]. The MenACWY-TT vaccine (Nimenrix®, Pfizer Ltd, Sandwich, UK) contains each meningococcal serogroup conjugated to tetanus toxoid (TT) as a carrier protein [8]. MenACWY-TT is licensed in at least 80 countries for vaccination of infants, children, adolescents, and adults against IMD caused by serogroups A, C, W, and Y. A 2-dose primary vaccination schedule is recommended in infants 6 weeks to 6 months of age (2 months between doses) with a booster dose at 12 months of age [8]. In children 6 months or older, a single-dose primary vaccination is recommended with a booster dose at 12 months of age (≥2 months after the primary dose) for children initially vaccinated between 6 and 12 months of age [8].

The immunogenicity and safety of primary MenACWY-TT vaccination in toddlers have been demonstrated in phase 2 and 3 clinical studies in which MenACWY-TT elicited protective immune responses for all vaccine serogroups [9], [10], [11]. However, antibody persistence to MenACWY vaccines can vary by age group [12]. For example, immune responses in adolescents to some MenACWY conjugate vaccines wane within 3–8 years after primary vaccination [13], [14]; antibody levels in young children may decline more rapidly and can vary by serogroup [12], [15]. Because the long-term persistence of antibody responses following primary MenACWY conjugate vaccination and the duration of protection following a booster of MenACWY have not been fully elucidated—particularly in children who received primary dosing as toddlers—additional booster vaccination may be required to prolong protection.

Over the last decade, an increasing number of studies have examined the long-term persistence of antibody responses with MenACWY-TT [16], [17], [18]. This article provides a review of the clinical data regarding the long-term persistence of antibody responses of MenACWY-TT in toddlers after primary and booster vaccination and summarizes the data descriptively without formal statistical evaluations. The implications of the findings are also discussed in this review.

Section snippets

Review of MenACWY-TT studies performed in toddlers

Four open-label, randomized clinical studies assessed the long-term antibody persistence and safety of MenACWY-TT in toddlers, including one phase 3 and three phase 2 studies (Table 1) [9], [10], [19], [20], [21], [22], [23], [24], [25]. The studies were conducted in Europe and the United States and included a total of 1921 healthy toddlers either 12–23, 12–14, or 9–12 months of age at the time of primary vaccination [9], [10], [20], [23]. Additionally, 477 subjects received booster vaccination

Persistence of antibody responses in toddlers after primary vaccination

The persistence of antibody responses to primary MenACWY-TT vaccination as measured by rSBA titers ≥1:8 are summarized in Fig. 1. In all studies, the percentage of subjects with antibody responses was high at 1 month or 42 days after receiving 1 or 2 primary MenACWY-TT doses [9], [10], [20], [23]. In Studies 1 and 4, the percentage of subjects with antibody responses decreased at 3 years after primary vaccination and stabilized at 4 years after primary dosing for Study 1 and at 5 years for

Persistence of antibody responses in toddlers after booster vaccination

Booster meningococcal vaccine doses were administered in 2 studies, at 4 years (Study 1) and 5 years (Study 4) after primary vaccination as toddlers [19], [24]. In both studies, protective antibody responses were observed after booster vaccination, with 100% of subjects in Studies 1 and 4 having rSBA titers and hSBA titers ≥1:8, respectively, at 1 month after MenACWY-TT booster dosing. The persistence of booster responses was assessed in Study 1, as described below.

Discussion

Meningococcal primary vaccination of toddlers, children, and adolescents is included in the national immunization program of several countries [27], [28], [29]. Vaccination against IMD is of critical importance in young children because of the high risk of IMD in this age group [1], [2]. Four separate toddler studies evaluating MenACWY-TT were reviewed to provide a comprehensive dataset of the persistence of primary and booster dosing of MenACWY in this age group [9], [10], [19], [20], [21],

Declaration of Competing Interest

The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests: All authors are employees of Pfizer and may hold stock or stock options.

Acknowledgments

Editorial/medical writing support was provided by Tricia Newell, PhD, and Kim Kridsada, PhD, of Complete Healthcare Communications, LLC (North Wales, PA), a CHC Group company, and was funded by Pfizer Inc.

Funding

This work was funded by Pfizer Inc.

Contributions

All authors attest that they meet the ICMJE criteria for authorship.

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  • Cited by (3)

    • Clinical trial and postmarketing safety experience with MenACWY-TT, a meningococcal group A, C, W, and Y tetanus conjugate vaccine

      2022, Vaccine
      Citation Excerpt :

      Licensure of MenACWY-TT was based on an extensive clinical development program that included randomized phase 2 and 3 clinical trials and postmarketing studies across age groups ≥ 6 weeks of age, which support the robust immunogenicity and acceptable safety profile (after primary or booster doses) of MenACWY-TT [3]. In addition, the persistence of antibody responses ≤ 10 years after primary MenACWY-TT vaccination of toddlers, children, adolescents, and adults [4–7] and ≤ 6 years after booster dosing of toddlers [8] has been reported. Along with its widespread use to protect against meningococcal serogroups A, C, W, and Y, MenACWY-TT is a constituent of an investigational pentavalent meningococcal vaccine (MenABCWY) currently undergoing clinical development.

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