518. Definition of a Correlate of Protection for Inactivated Influenza Vaccines in Children less than Five Years of Age: Difference Between a Seasonal Correlate and a Challenge Model
Session: Poster Abstract Session: Influenza Vaccines
Friday, October 21, 2011
Room: Poster Hall B1
  • Poster ISDA for print.pdf (904.3 kB)
  • Background:  The HAI titer of 1:40 which has been recognized as an immunologic correlate corresponding to a 50% reduction in the risk of contracting influenza in adult and elderly populations is based largely on challenge studies. Neither seasonal nor challenge based correlates have been evaluated in children.  

    Methods: 4707 healthy influenza vaccine naive children 6-72 months old were randomized 2:2:1 to receive MF59-adjuvanted influenza vaccine (Fluad™,ATIV, Novartis Vaccines), split TIV (TIV control, GSK), or a non-influenza vaccine during the 2007-2008 and 2008-2009 influenza seasons.  Cases of ILI identified by active surveillance were confirmed by RT-PCR testing for influenza. Immunogenicity at day 50 following dose one was evaluated in a subset of 777 children. 

    Results: Immunogenicity and efficacy results for H3N2 were evaluated against the Prentice criteria which confirmed that the immunogenicity warranted estimation of an immunologic correlate.  We then used the Dunning model fitting the H3N2 antibody levels at day 50 and the influenza cases observed in the immunogenicity subset revealed that a cut-off HAI titer of 1:110 was associated with the conventional 50% clinical protection rate against infection during the entire season and titers of  1:215, 1:330 and 1:629 predicated  protection rates of 70%, 80% and 90% respectively. The conventional adult 1:40 HAI titer was only associated with 22% protection. We also estimated the titer required for 50% and 80% protection at the time of exposure to be 1:85 (95% CI= 35.6-137.9) and 1:302 (95% CI=177-439) respectively.

    Conclusion: The use of the 1:40 HAI adult correlate of protection is not appropriate when evaluating influenza vaccines in children. Although a cut-off of 1:110 may be used to predict the conventional 50% clinical protection rate, a titer of 1:330 would predict an 80% protective level which would seem to be more desirable from a public health perspective.

    Subject Category: I. Adult and Pediatric Vaccines

    Steven Black, MD1, Uwe Nicolay, MS2, Timo Vesikari, Professor3, Marcus Knuf, MD4, Giuseppe Del Giudice, M. D. 2, Giovanni della Cioppa, MD2, Theodore Tsai, MD5, Ralf Clemens6 and Rino Rappuoli, MD2, (1)Center for Global Health, University of Cincinnati Children's Hospital, Cincinnati, OH, (2)Novartis Vaccines, Siena, Italy, (3)University of Tampere , Tampere, Finland, (4)Johannes Gutenberg-Universitšt, Mainz, Germany, (5)Novartis Vaccines and Diagnostics, Boston, MA, (6)Novartis Vaccines & Diagnostics GmBH & Co. KG, Marburg, Germany


    S. Black, Novartis Vaccines: Independent Contractor, Consulting fee

    U. Nicolay, Novartis Vaccines: Employee, Salary

    T. Vesikari, Novartis Vaccines: Consultant and Investigator, Consulting fee and Grant recipient
    GSK: Consultant and Investigator, Consulting fee and Grant recipient
    Pfizer: Consultant, Consulting fee

    M. Knuf, Novartis Vaccines: Grant Investigator, Grant recipient

    G. Del Giudice, Novartis Vaccines: Employee, Salary

    G. della Cioppa, Novartis Vaccines: Employee, Salary

    T. Tsai, Novartis Vaccines: Employee, Salary

    R. Clemens, Novartis Vaccines: Board Member and Employee, Salary

    R. Rappuoli, Novartis Vaccines: Employee, Salary

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