Evaluation of the Induction of Immune Memory following Infant Immunisation with Serogroup C Neisseria meningitidis Conjugate Vaccines – Exploratory Analyses within a Randomised Controlled Trial

Abstract

AimWe measured meningococcal serogroup C (MenC)-specific memory B-cell responses in infants by Enzyme-Linked Immunospot (ELISpot) following different MenC conjugate vaccine schedules to investigate the impact of priming on immune memory.MethodsInfants aged 2 months were randomised to receive 1 or 2 doses of MenC-CRM197 at 3 or 3 and 4 months, 1 dose of MenC-TT at 3 months, or no primary MenC doses. All children received a Haemophilus influenzae type b (Hib)-MenC booster at 12 months. Blood was drawn at 5, 12, 12 months +6 days and 13 months of age.ResultsResults were available for 110, 103, 76 and 44 children from each group respectively. Following primary immunisations, and prior to the 12-month booster, there were no significant differences between 1- or 2-dose primed children in the number of MenC memory B-cells detected. One month following the booster, children primed with 1 dose MenC-TT had more memory B-cells than children primed with either 1-dose (p = 0.001) or 2-dose (p<0.0001) MenC-CRM197. There were no differences in MenC memory B-cells detected in children who received 1 or 2 doses of MenC-CRM197 in infancy and un-primed children.ConclusionsMenC-specific memory B-cell production may be more dependent on the type of primary vaccine used than the number of doses administered. Although the mechanistic differences between MenC-CRM197 and MenC-TT priming are unclear, it is possible that structural differences, including the carrier proteins, may underlie differential interactions with B- and T-cell populations, and thus different effects on various memory B-cell subsets. A MenC-TT/Hib-MenC-TT combination for priming/boosting may offer an advantage in inducing more persistent antibody.Trial RegistrationEU Clinical Trials Register 2009-016579-31 ClinicalTrials.gov NCT01129518

Human Infant Memory B Cell and CD4+ T Cell Responses to HibMenCY-TT Glyco-Conjugate Vaccine

“…The significantly greater number of Men C- and Men Y- specific memory B cells at M7 compared to M6 is likely reflective of the time of blood sampling post vaccination, where M6 samples are 2 months following the previous dose of vaccine and M7 are 1 month post the previous dose of vaccine. Whilst a recent study comparing several Men C glyco-conjugate vaccines has shown an increase in the number of memory B cells from post-prime to pre-boost [ 12 ], we have not seen this in our study. This could be due to differences in the vaccines used, or the length of time between post-prime and pre-boost time-points.…”

“…A number of studies in animal models have identified that B cells primed at initial antigen encounter can become either memory B cells or plasma cells, the latter of which are terminally differentiated and short- or long- lived [ 4 , 5 ]. In studies of glyco-conjugate vaccines, polysaccharide-specific plasma cells [ 6 ] and memory B cells [ 6 – 12 ] have been measured in the peripheral blood following priming and booster doses, and two studies in infants have identified that Men C-specific memory B cells present post-priming are good predictors of the persistence of Men C-specific IgG at 12 months prior to boosting [ 7 , 11 ].…”

Immunogenicity of reduced dose priming schedules of serogroup C meningococcal conjugate vaccine followed by booster at 12 months in infants: open label randomised controlled trial

“…Intriguingly, priming with a single MenC-CRM dose induced higher post-Hib-MenC-TT rSBA geometric mean titres than two priming doses, suggesting that the administration of a greater amount of MenC antigen during priming reduces the subsequent immune response to the 12 month MenC conjugate vaccine booster dose. The underlying mechanism, which is not reflected in the frequencies of MenC-specific memory B cells in peripheral blood detected at 5, 12, or 13 months,20 could still be related to differences in numbers of memory B cells if the pool is considered to be resident in lymphoid tissues and therefore inaccessible with peripheral blood sampling. Furthermore, this phenomenon might be the result of dose dependent differences in carrier protein that manifest when different MenC glycoconjugate vaccine formulations are used for priming and boosting.…”

Is a single infant priming dose of meningococcal serogroup C conjugate vaccine in the United Kingdom sufficient?

“…The memory B cells measured by ELISpot in the peripheral blood at 5 months of age following a single dose of NeisVac-C Ò at 3 months of age were compared to 2 doses of Menjugate Ò at 3 and 4 months of age. 19 Responses following a booster dose, showed significantly higher SBA GMTs following boosting in those primed with a single dose of NeisVac-C Ò at 3 months of age compared to 2 doses of Menjugate Ò at 3 and 4 months of age. Children who had been primed with NeisVac-C Ò produced the greatest memory B cell response to the Menitorix Ò booster.…”

“…18,19 Infants were vaccinated with a single dose of either Menjugate Ò or NeisVac-C Ò at 3 months of age, compared to 2 doses of Menjugate Ò at 3 and 4 months of age. Blood samples collected at 5 months of age, showed the SBA GMT to be significantly higher in the 2 dose Menjugate Ò group (GMT of 618.3 (95%CI 538.3-710.1), compared to 53 (95%CI 39.9-70.5) and 155.4 (95%CI 112.3-213.8) in those who received one dose of Menjugate Ò or NeisVac-C Ò , respectively.…”