Baker, S.

Daniels, E.

Dymond, S.

Faust, S.N.

Finn, A.

Galiza, E.

Gruber, W.

Heath, P.T.

John, T.

Klinger, C.

Layton, H.

Pestridge, S.

Pollard, A.

Scott, D.

Snape, M.

Tansey, S.

English

Southampton (e-Prints Soton)

ABSTRACTBackgroundStreptococcus  pneumoniae is  a  leading  cause  of  morbidity  and  mortality  in  children worldwide.  Although  the  7-valent  pneumococcal  conjugate  vaccine  (PCV7)  has  been successful in controlling pneumococcal disease, some disease-causing serotypes are not covered by this vaccine. We report the infant series results of a randomised, double-blind, active-controlled  study  of  a  13-valent-pneumococcal  vaccine  (PCV13),  containing polysaccharides  from  serotypes  1,  3,  4,  5,  6A,  6B,  7F,  9V,  14,  18C,  19A,  19F,  23F individually conjugated to CRM197.Methods278 healthy infants aged 6 -14 weeks were enrolled and randomised 1:1 to receive PCV13 or  PCV7  at  2  and  4  months.  Participants  received  serogroup  C  meningococcal  (MenC) vaccine  at  2  and  4  months  and  DTaP-IPV-Hib vaccine  at  age  2,  3,  and  4  months. Concomitant antibody responses in both groups and PCV13 responses in the PCV13 group were assessed at 5 months.ResultsConcomitant  antibody  responses  were  comparable  in  the  2  groups.  Anti-PRP  IgG concentration ≥ 0.15 μg/ml was achieved by 96.5% of the PCV13 group and 98.1% of the PCV7 group. MenC SBA titres of ≥ 1:8 were achieved by 99.2% of participants in both. All participants in both groups achieved IgG concentrations ≥ 5 EU/mL for pertussis antigens PT, FHA and Pertactin. The proportion of participants in the PCV13 group with serotype specific  IgG  concentrations  ≥0.35µg/mL  ranged  from  40.7%  (serotype  6B)  to  96.3% (serotype 1). PCV7 and PCV13 were well tolerated with comparable reactogenicity profiles.ConclusionsImmunogenicity of concomitant antigens is comparable when administered with either PCV7 or PCV13 in a UK primary infant series.G-2118  Immunogenicity Of  Immunogenicity Of DTaP DTaP- -IPV IPV- -Hib Hib And MenC Vaccines In The UK When  And MenC Vaccines In The UK When Administered With a 13 Administered With a 13- -valent Pneumococcal Conjugate Vaccine valent Pneumococcal Conjugate VaccineC. L. KLINGER1, M. D. SNAPE 1, T. JOHN 1, H. LAYTON 1, E. DANIELS 2, S. TANSEY 2, D. SCOTT 2, S. BAKER 2, W. GRUBER 2, S. N. FAUST 3, S. PESTRIDGE 3, A. FINN 4, S. DYMOND 4, P. T. HEATH 5, E. GALIZA 5, A. J. POLLARD 1; 1University of Oxford, UK, 2Wyeth Vaccines, NY, NY, 3 University of Southampton, UK, 4 University of Bristol, UK, 5 University of London, UK.INTRODUCTION• The 7 valent pneumococcal conjugate vaccine (PCV7) has successfully reduced invasive pneumococcal disease in the countries where it has been introduced1.• Significant disease causing serotypes such as serotypes 1, 3 and 19A are not included in this vaccine, with a suboptimal coverage of the global pneumococcal disease burden2.• A novel 13 valent pneumococcal conjugate vaccine (PCV13) has been developed and was assessed in this multi-centred double blind randomised controlled trial • The study was sponsored by Wyeth VaccinesOBJECTIVES• To  evaluate  the  proportion  of  participants  achieving  predetermined  thresholds  for concomitant antigens 1 month after the infant series • To evaluate the safety and reactogenicity of PCV13• To assess the antibody response of participants receiving a 2 and 4 month course of PCV 13CONCLUSIONS AND DISCUSSION• PCV13 was immunogenic and well tolerated when given as part of  the UK infant vaccine course.• The  percentages  of  participants  achieving  the  thresholds  of  response  for  the  concomitant  antigens were comparable between the two groups.• PCV13  vaccination  at  2  and  4  months  resulted  in  78.5  - 96.3%  of  vaccinees achieving  the correlate of protection for the 6 additional serotypes not contained in PCV7.• 91%  of  PCV13  recipients  achieved  the  threshold  of  protection  against  Serotype  19A,  a predominant invasive pneumococcal serotype in the USA.• PCV13  offers  the  potential  to  broaden  the  immune  protection  against  invasive  pneumococcal disease afforded by the currently licensed pneumococcal conjugate vaccine.Contact detailsDr Matthew Snape,Consultant in Vaccinology,University of Oxford,Oxford Vaccine Group, CCVTM,Churchill Hospital, Oxford.UK.  OX3 7LJ.STUDY DESIGNRandomised 1:1PCV13 GroupPCV13: 2, 4 monthsMenC: 2,4 monthsDTaP-IPV-Hib: 2,3,4 monthsPCV7 groupPCV7: 2,4 monthsMenC: 2,4 monthsDTaP-IPV-Hib: 2,3,4 monthsFigure 1: Percentage of participants achieving prespecified antibody concentrations after infant series of  concomitant vaccines. Error bars represent 95%C.I.Figure 4: Systemic reactions within 4 days of vaccination020406080100Percentage participantsPCV-13 PCV-7Dose 1   Dose 2Fever 38-39Dose 1   Dose 2Fever >40Dose 1   Dose 2Dec appetiteDose 1   Dose 2IrritabilityDose 1   Dose 2Inc. sleepDose 1   Dose 2Dec sleepFigure 5: Local reactions reported by participants within 4 days of vaccinationDose 1       Dose 2TendernessDose 1         Dose 2Induration0102030405060708090100Percentage of participantsDose 1         Dose 2ErythemaPCV 13PCV 7Severe reactions020406080100Percentage of participantsPCV-13PCV-7Hib MenC Pertussis≥ 0.15 µg/ml≥ 1.0 µg/mlrSBA ≥ 1:8PT ≥ 5 EU/mLFHA ≥ 5 EU/mLFIM ≥ 5 EU/mLPertactin ≥ 5 EU/mLACKNOWLEDGMENTSThe authors thank the participants of this study and their families. They also wish to acknowledge the following co-investigators: Dr David Weston, Dr Malcolm McCaughey, Dr Timothy Hall, Dr Katrina Young, Dr Anthony Egerton.RESULTS• 278 infants were enrolled; 139 to the PCV13 group (mean age 2.1 months, 56% male) and 139 to PCV7 group (mean age 2.1 months, 46% male)• 135 (PCV13) and 132 (PCV7) completed the infant stage of the study• Immunogenicity  results  for  the  concomitant  vaccines  are  shown  in  Figure  1  (concomitant vaccines) and Figures 2 and 3 (PCV13), while PCV13 reactogenicity is shown in Figures 4 and 5REFERENCES1 Black S et  al. Postlicensure surveillance for pneumococcal invasive disease after use of heptavalent pneumococcal conjugate vaccine in Northern California Kaiser Permanente. Pediatr Infect Dis J 2004;23:485-9.2 Tsai CJ et  al. Changing epidemiology of pneumococcal meningitis after the introduction of pneumococcal conjugate vaccine in the United States. Clin Infect Dis 2008;46:1664-72.3 World Health Organization. Recommendations for the production and control of pneumococcal conjugate vaccines. WHO Technical Report Series, No. 927, 2005Figure 3: Percentage of participants in the PCV13 group achieving IgG ≥ 0.35 mcg/ml for each pneumococcal serotype0204060801004 6B 9V 14 18C 19F 23F 1 3 5 6A 7F 19APercentage >= 0.35mcg/mlFigure 2: Pneumococcal immunogenicity for the PCV13 group after dose 2 of the infant series (IgG GMC)00.511.522.533.54 6B 9V 14 18C 19F 23F 1 3 5 6A 7F 19AIgG GMC mcg/mlPneumococcal serotypeSerotypes covered in PCV7 and PCV13Serotypes covered in PCV13 alonePneumococcal serotype• Pneumococcal serotype specific IgG was measured by standardised ELISA with a correlate of protection of ≥ 0.35 mcg/ml3

Changing epidemiology of pneumococcal meningitis after the introduction of pneumococcal conjugate vaccine in the United States. Clin Infect Dis

Organization. Recommendations for the production and control of pneumococcal conjugate vaccines.

Postlicensure surveillance for pneumococcal invasive disease after use of heptavalent pneumococcal conjugate vaccine in Northern California Kaiser Permanente. Pediatr Infect Dis

Immunogenicity of DTaP-IPV-Hib and MenC vaccines in the UK when administered with a 13-valent pneumococcal conjugate vaccine

Immunogenicity of DTaP-IPV-Hib and MenC vaccines in the UK when administered with a 13-valent pneumococcal conjugate vaccine

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