Multivariate analysis of the immune response to a vaccine as an alternative to the repetition of animal challenge studies for vaccines with demonstrated efficacy

Ludivine Chapat, Florence Hilaire, Jérome Bouvet, Daniel Pialot, Corinne Philippe-Reversat, Anne-Laure Guiot, Lydie Remolue, Jacques Lechenet, Christine Andreoni, Hervé Poulet, Michael J. Day, Karelle De Luca, Carine Cariou, Lionel Cupillard

Research output: Contribution to journalArticle (Academic Journal)peer-review

7 Citations (Scopus)

Abstract

Abstract The assessment of vaccine combinations, or the evaluation of the impact of minor modifications of one component in well-established vaccines, requires animal challenges in the absence of previously validated correlates of protection. As an alternative, we propose conducting a multivariate analysis of the specific immune response to the vaccine. This approach is consistent with the principles of the 3Rs (Refinement, Reduction and Replacement) and avoids repeating efficacy studies based on infectious challenges in vivo. To validate this approach, a set of nine immunological parameters was selected in order to characterize B and T lymphocyte responses against canine rabies virus and to evaluate the compatibility between two canine vaccines, an inactivated rabies vaccine (RABISIN®) and a combined vaccine (EURICAN® DAPPi-Lmulti) injected at two different sites in the same animals. The analysis was focused on the magnitude and quality of the immune response. The multi-dimensional picture given by this ‘immune fingerprint’ was used to assess the impact of the concomitant injection of the combined vaccine on the immunogenicity of the rabies vaccine. A principal component analysis fully discriminated the control group from the groups vaccinated with RABISIN® alone or RABISIN® + EURICAN® DAPPi-Lmulti and confirmed the compatibility between the rabies vaccines. This study suggests that determining the immune fingerprint, combined with a multivariate statistical analysis, is a promising approach to characterizing the immunogenicity of a vaccine with an established record of efficacy. It may also avoid the need to repeat efficacy studies involving challenge infection in case of minor modifications of the vaccine or for compatibility studies.
Original languageEnglish
JournalVeterinary Immunology and Immunopathology
Early online date15 Jun 2017
DOIs
Publication statusE-pub ahead of print - 15 Jun 2017

Keywords

  • RABIES VACCINE
  • RABISIN®
  • IMMUNE FINGERPRINT
  • PRINCIPLE COMPONENT ANALYSIS
  • 3Rs

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