https://www.um.edu.mt/library/oar/handle/123456789/288 2026-04-10T14:01:10Z https://www.um.edu.mt/library/oar/handle/123456789/135427 Title: 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 Authors: Pace, David; Khatami, Ameneh; McKenna, Jennifer; Campbell, Danielle; Attard-Montalto, Simon; Birks, Jacqueline; Voysey, Merryn; White, Catherine; Finn, Adam; Macloed, Emma; Faust, Saul N.; Kent, Alison Louise; Heath, Paul T.; Borrow, Ray; Snape, Matthew D.; Pollard, Andrew J. Abstract: Objective: To determine whether the immunogenicity of a single dose infant priming schedule of serogroup C meningococcal (MenC) conjugate vaccine is noninferior to a two dose priming schedule when followed by a booster dose at age 12 months.; Design: Phase IV open label randomised controlled trial carried out from July 2010 until August 2013; Setting: Four centres in the United Kingdom and one centre in Malta.; Participants: Healthy infants aged 6–12 weeks followed up until age 24 months.; Interventions: In the priming phase of the trial 509 infants were randomised in a 10:10:7:4 ratio into four groups to receive either a single MenC-cross reacting material 197 (CRM) dose at 3 months; two doses of MenC-CRM at 3 and 4 months; a single MenC-polysaccharidetetanus toxoid (TT) dose at 3 months; or no MenC doses, respectively. Haemophilus influenzae type b (Hib)-MenC-TT vaccine was administered to all infants at 12 months of age. All infants also received the nationally routinely recommended vaccines. Blood samples were taken at age 5, 12, 13, and 24 months.; Main outcome measure: MenC serum bactericidal antibody assay with rabbit complement (rSBA) one month after the Hib-MenC-TT vaccine. Non-inferiority was met if the lower 95% confidence limit of the difference in the mean log10 MenC rSBA between the single dose MenC-CRM and the two dose MenC-CRM groups was >−0.35.; Results: The primary objective was met: after a Hib-MenC-TT booster dose at 12 months of age the MenC rSBA geometric mean titres induced in infants primed with a single MenC-CRM dose were not inferior to those induced in participants primed with two MenC-CRM doses in infancy (660 (95% confidence interval 498 to 876) v 295 (220 to 398)) with a corresponding difference in the mean log10 MenC rSBA of 0.35 (0.17 to 0.53) that showed superiority of the single over the two dose schedule). Exploration of differences between the priming schedules showed that one month after Hib-MenC-TT vaccination, MenC rSBA ≥1:8 was observed in >96% of participants previously primed with any of the MenC vaccine schedules in infancy and in 83% of those who were not vaccinated against MenC in infancy. The MenC rSBA geometric mean titres induced by the Hib-MenC-TT boost were significantly higher in children who were primed with one rather than two MenC-CRM doses in infancy. Only priming with MenC-TT, however, induced robust MenC bactericidal antibody after the Hib-MenC-TT booster that persisted until 24 months of age.; Conclusions: MenC vaccination programmes with two MenC infant priming doses could be reduced to a single priming dose without reducing post-boost antibody titres. When followed by a Hib-MenC-TT booster dose, infant priming with a single MenC-TT vaccine dose induces a more robust antibody response than one or two infant doses of MenC-CRM. Bactericidal antibody induced by a single Hib-MenC-TT conjugate vaccine dose at 12 months of age (that is, a toddler only schedule), without infant priming, is not well sustained at 24 months. Because of rapid waning of MenC antibody, programmes using toddler only schedules will still need to rely on herd protection to protect infants and young children. 2015-01-01T00:00:00Z https://www.um.edu.mt/library/oar/handle/123456789/135413 Title: Meningococcal serogroup Y disease in Europe : continuation of high importance in some European regions in 2013 Authors: Bröker, Michael; Emonet, Stéphane; Fazio, Cecilia; Jacobsson, Susanne; Koliou, Maria; Kuusi, Markku; Pace, David; Paragi, Metka; Pysik, Alexander; Simões, Maria João; Skoczynska, Anna; Stefanelli, Paola; Toropainen, Maija; Taha, Muhamed-Kheir; Tzanakak, Georgina Abstract: Neisseria meningitidis or meningococcus is divided into 12 distinct serogroups of which A, B, C, W, X, and Y are medically most important and cause health problems in different parts of the world. The epidemiology of N. meningitidis is unpredictable over time and across geographic regions. Globally, serogoup A has been prevalent in the African “meningitis belt” whereas serogroup B and C have predominated in Europe. In a paper published earlier in this journalCitation1, an increase in serogroup Y invasive meningococcal disease (IMD) in some European countries was reported based on the epidemiological data for 2010, 2011 and 2012. Here, we report additional data from 30 European countries indicating that high or increased serogroup Y disease levels have continued in 2013 in certain regions of Europe. In the Western and Central Europe, there were no major changes in the proportion of serogroup Y IMD cases in 2013 compared to 2012. In the Scandinavian countries, proportion of serogroup Y disease remained high, ranging from 26% to 51% in 2013. This was in contrast to Baltic, Eastern and most Southern European countries, where the proportion of serogroup Y IMD was low similarly to previous years. For the last 2 decades, the mean age of patients affected by serogroup Y was 41 y for 7 countries from which data was available and 50% of cases were in patients aged 45 to 88 y. The age distribution of serogroup Y was bimodal and did not change significantly despite the increase of the total number and the proportion of serogroup Y IMD in some European regions. 2015-01-01T00:00:00Z https://www.um.edu.mt/library/oar/handle/123456789/132065 Title: Meningococcal serogroup Y emergence in Europe : update 2011 Authors: Bröker, Michael; Jacobsson, Susanne; Kuusi, Markku; Pace, David; Simões, Maria J.; Skoczynska, Anna; Taha, Muhamed-Kheir; Toropainen, Maija; Tzanakaki, Georgina Abstract: Neisseria meningitidis is differentiated into 12 distinct serogroups, of which A, B, C, W-135, X and Y are medically most important and represent an important health problem in different parts of the world. The epidemiology of N. meningitidis is unpredictable over time and across geographic regions. Recent epidemiological surveillance has indicated an increase of serogroup Y invasive meningococcal disease in some parts of Europe as shown in the epidemiological data for 2010 from various European countries previously published in this journal. Here, data is reported indicating that the emergence of serogroup Y continued in 2011 in various regions of Europe. The average age of persons affected by N. meningitidis serogroup Y seems to have decreased in some countries in comparison to the previous decade. 2012-01-01T00:00:00Z https://www.um.edu.mt/library/oar/handle/123456789/132014 Title: Immunological effect of administration of sequential doses of Haemophilus influenzae type b and pneumococcal conjugate vaccines in the same versus alternating limbs in the routine infant immunisation schedule : an open-label randomised controlled trial Authors: Iro, Mildred A.; Khatami, Ameneh; Marshall, Andrew S. J.; Pace, David; Voysey, Merryn; McKenna, Jennifer; Campbell, Danielle; Attard-Montalto, Simon; Finn, Adam; White, Catherine; Faust, Saul N.; Kent, Alison; Heath, Paul T.; MacLeod, Emma; Stanford, Elaine; Findlow, Helen; Almond, Rachael; Bai, Xilian; Borrow, Ray; Snape, Matthew D.; Pollard, Andrew J. Abstract: Background: The use of different limbs for the administration of sequential doses of an intradermal rabies vaccine was shown to result in reduced vaccine immunogenicity. We aimed to assess whether this phenomenon also occurs with routine infant vaccines. Methods: In this open-label, randomised, controlled study, eligible healthy infants 6–12 weeks of age recruited through five clinical trials units (four in the UK and one in Malta) were randomly assigned in a 1:1 ratio to two vaccination groups: consistent limb or alternating limb. Infants in the consistent limb group received the diphtheria–tetanus–acellular pertussis–inactived polio–Haemophilus influenzae type b combined vaccine (DTaP–IPV–Hib) at 2, 3, and 4 months of age, and the pneumococcal conjugate vaccine (PCV13) at 2, 4, and 12 months, all administered to the right leg. Infants in the alternating limb group received DTaP–IPV–Hib in the left leg at 2 months and in the right leg at 3 and 4 months; and PCV13 in the left leg at 2 months, in the right leg at 4 months, and in the left arm at 12 months. All infants in both groups received the combined H influenzae type b and capsular group C Neisseria meningitidis tetanus toxoid conjugate vaccine (Hib–MenC–TT), administered in the left leg at 12 months. Randomisation was achieved by randomly generated codes, with permuted block size of 30, and was stratified by study site. Group allocation was not masked from study staff and parents of participants after enrolment, but group allocation was masked from laboratory staff assessing blood samples. The current study was a prespecified secondary objective of a parent phase 4 trial that assessed the induction of immunity following varying schedules of vaccination with glyco-conjugate capsular group C Neisseria meningitidis (Men C) vaccines in infancy. The objective of the current study was to compare the immunogenicity and reactogenicity of vaccines delivered in either consistent or alternating limbs. Immunogenicity was assessed by comparing serum IgG geometric mean concentrations at 5, 12, 13, and 24 months, analysed per protocol. This study is registered with ClinicalTrials.gov, number NCT01129518. Findings: Between July 5, 2010, and Aug 1, 2013, we enrolled 509 infants and randomly allocated them to the consistent limb group (n=254) or the alternating limb group (n=255). Anti-H influenzae type b anti-polyribosylribitol phosphate IgG geometric mean concentrations were lower in the consistent limb group than in the alternating limb group at 5 months (consistent limb 0·41 μg/mL [95% CI 0·31–0·54] vs alternating limb 0·61 μg/mL [0·45–0·82]; p=0·0268) and at 12 months (0·35 μg/mL [0·28–0·43] vs 0·50 μg/mL [0·40–0·62]; p=0·0136). Anti-tetanus toxoid antibody IgG geometric mean concentrations were lower in the consistent limb group (1·63 IU/mL [95% CI 1·40–1·90]) than in the alternating limb group (2·30 IU/mL [1·97–2·68]) at 13 months (p=0·0008) and at 24 months (0·44 IU/mL [0·37–0·52] vs 0·61 IU/mL [0·51–0·73]; p=0·0074). Anti-pneumococcal IgG geometric mean concentrations were similar between both groups at all timepoints. The proportions of participants who had adverse events did not differ between the two groups. Interpretation: Use of different (alternating) limbs for sequential doses of routine infant vaccines does not reduce, and might enhance, immunogenicity. The underlying mechanism for this finding warrants further research. 2015-01-01T00:00:00Z