ReviewPersistence of bactericidal antibodies following primary and booster MenACWY-TT vaccination of toddlers: A review of clinical studies
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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Clinical trial and postmarketing safety experience with MenACWY-TT, a meningococcal group A, C, W, and Y tetanus conjugate vaccine
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