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The clinical development of the meningococcal vaccine, 4CMenB, included 2 doses in vaccine-naïve adolescents, which was considered unlikely to be cost-effective for implementation. Theoretically, priming with 4CMenB in early childhood might drive strong immune responses after only a single booster dose in adolescents and reduce programmatic costs. To address this question, children over 11 years old who took part in previous trials involving the administration of 3-5 doses of 4CMenB at infant/preschool age from 2006 were recruited into a post licensure single-centre trial, and were divided into two groups: those who received their last dose at 12 months old (infant group) and those who received their last dose at 3 years old (infant + preschool group). Naïve age-matched controls were randomised to receive one (adolescent 1 group) or two doses at days 0 and 28 (adolescent 2 group) of 4CMenB. Serum bactericidal antibody (SBA) assays using human complement were performed against three reference strains prior to vaccination, and at 1, 6 and 12 months. Previous vaccination was associated with a higher response to a single booster dose at 11 years of age, one-month post-vaccination, when compared with a single dose in naïve age-matched controls. At day 180, the highest responses were observed in participants in the infant + preschool group against strain 5/99 (GMT 316.1 [CI 158.4 to 630.8]), as compared with naïve adolescents who received two doses (GMTs 84.5 [CI 57.7 to 123.6]). When the last dose was received at 12-months of age, responses to a single adolescent dose were not as robust (GMT 61.1 [CI 14.8 to 252.4] to strain 5/99). This descriptive study indicates that the highest SBA responses after a single dose in adolescence were observed in participants who received a preschool dose, suggesting that B cell memory responses are not sufficiently primed at less than 12 months of age. Trial registration EudraCT 2017-004732-11, ISRCTN16774163., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Mucosal-associated invariant T (MAIT) cells are innate sensors of viruses and can augment early immune responses and contribute to protection. We hypothesized that MAIT cells may have inherent adjuvant activity in vaccine platforms that use replication-incompetent adenovirus vectors. In mice and humans, ChAdOx1 (chimpanzee adenovirus Ox1) immunization robustly activated MAIT cells. Activation required plasmacytoid dendritic cell (pDC)-derived interferon (IFN)-α and monocyte-derived interleukin-18. IFN-α-induced, monocyte-derived tumor necrosis factor was also identified as a key secondary signal. All three cytokines were required in vitro and in vivo. Activation of MAIT cells positively correlated with vaccine-induced T cell responses in human volunteers and MAIT cell-deficient mice displayed impaired CD8 + T cell responses to multiple vaccine-encoded antigens. Thus, MAIT cells contribute to the immunogenicity of adenovirus vectors, with implications for vaccine design., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background and Rationale: The four-component capsular group B meningococcal vaccine (4CMenB) was introduced into the national immunisation schedule in the UK in September 2015 for infants in a 2 + 1 schedule at two, four and 12 months of age. A two-dose immunisation schedule for adolescents was also considered but was not found to be cost-effective in view of the relatively low rates of disease in this age group. Uncertainty about the longevity of protection induced by the vaccine and lack of certainty about an anamnestic response in primed individuals contributed to this decision., Methods/design: This study is an open-label, descriptive immunogenicity analysis. Up to 113 participants will be recruited, including up to 83 children who are now aged 11 years and took part in previous trials involving the administration of 4CMenB to infants, plus a group of 30 naïve age-matched controls. All previously immunised participants will receive one booster dose of 4CMenB. The 30 naïve participants will be randomised to receive two doses of 4CMenB either at 0 and 28 days or 0 and 365 days. Blood samples will be collected from all participants at 0, 28, 180 and 365 days. The primary endpoint will explore immunogenicity at day 0 and 180 in previously immunised and naïve participants. Secondary outcomes will include investigating the persistence of antibody protection in previously immunised participants at the beginning of the study, describing the characteristics of the memory B-cell responses in previously immunised participants, and measuring reactogenicity in all participants following 4CMenB doses., Discussion: This study aims to describe whether or not a single booster dose of 4CMenB given to those who have received an infant course of 4CMenB induces a recall immune response, while concurrently describing immune responses in naïve children of the same age. If an anamnestic response is proven, a single dose adolescent booster could be envisaged as an addition to the current UK vaccination schedule., Trial Registration: EudraCT, 2017-004732-11. ISRCTN, ISRCTN16774163. Registered on 10 May 2018 (retrospectively registered).

Viral vectors are the vaccine platform of choice for many pathogens that have thwarted efforts towards control using conventional vaccine approaches. Although the STEP trial encumbered development of recombinant human adenovirus vectors only a few years ago, replication-deficient simian adenoviruses have since emerged as a crucial component of clinically effective prime-boost regimens. The vectors discussed here elicit functionally relevant cellular and humoral immune responses, at extremes of age and in diverse populations. The recent Ebola virus outbreak highlighted the utility of viral vectored vaccines in facilitating a rapid response to public health emergencies. Meanwhile, technological advances in manufacturing to support scale-up of viral vectored vaccines have helped to consolidate their position as a leading approach to tackling 'old' and emerging infections., (Copyright © 2016. Published by Elsevier Ltd.)