Nine μg intradermal influenza vaccine and 15 μg intramuscular influenza vaccine induce similar cellular and humoral immune responses in adults

Abstract

Intanza® 9 μg (Sanofi Pasteur), a trivalent split-virion vaccine administered by intradermal (ID) injection, was approved in Europe in 2009 for the prevention of seasonal influenza in adults 18 to 59 years. Here, we examined the immune responses induced in adults by the ID 9 μg vaccine and the standard trivalent intramuscular (IM) vaccine (Vaxigrip® 15 μg, Sanofi Pasteur). This trial was a randomized, controlled, single-center, open-label study in healthy adults 18 to 40 years of age during the 2007/8 influenza season. Subjects received a single vaccination with the ID 9 μg (n = 38) or IM 15 μg (n = 42) vaccine. Serum, saliva, and peripheral blood mononuclear cells were collected up to 180 days post-vaccination.

Geometric mean hemagglutination inhibition titers, seroprotection rates, seroconversion rates, and pre-vaccination-to-post-vaccination ratios of geometric mean hemagglutination inhibition titers did not differ between the two vaccines. Compared with pre-vaccination, the vaccines induced similar increases in vaccine-specific circulating B cells at day 7 but did not induce significant increases in vaccine-specific memory B cells at day 180. Cell-mediated immunity to all three vaccine strains, measured in peripheral blood mononuclear cells, was high at baseline and not increased by either vaccine. Neither vaccine induced a mucosal immune response. These results show that the humoral and cellular immune responses to the ID 9 μg vaccine are similar to those to the standard IM 15 μg vaccine.

Keywords:

• intradermal influenza vaccine
• intramuscular vaccination
• immunogenicity
• trivalent influenza vaccine
• adult

Abbreviations:

• BSA, bovine serum albumin
• CHMP, Committee for Medicinal Products for Human Use
• ELISA, enzyme-linked immunosorbent assay
• ELISPOT, enzyme-linked immunospot
• HI, hemagglutination inhibition
• ID, intradermal
• Ig, immunoglobulin
• IM, intramuscular
• PBMC, peripheral blood mononuclear cells
• PBS, phosphate-buffered saline

Disclosure of Potential Conflicts of Interest

N.N., H.B., and F.B. are employees of Sanofi Pasteur; P.L. was an employee of BD Medical Pharmaceutical Systems during realization of this study; A.R., C.G., B.V., K.R., A.H., and J.-F.N. are/were employees of one or several of the following public institutions in Lyon: INSERM U1111, IFR128, Claude Bernard University, and Hospices Civils.

Acknowledgments

The authors are grateful to Marie-Jose Quentin-Millet (Sanofi Pasteur) for supporting the present study and Dominique Kaiserlian (INSERM) for helpful advice. The authors also thank the patients and clinical staff at the Centre Hospitalier Lyon-Sud. The authors would also like to thank Francoise Weber (Sanofi Pasteur) for her work as clinical team leader of this clinical trial, Audrey Mamessier, Muriel Thenadey, and Emilie Proust (Sanofi Pasteur) for technical assistance, the staff from the Global Clinical Immunology (Sanofi Pasteur) for assisting with the HI assay, the Unite de Recherche Clinique en Immunologie for patient recruitment, Martine Denis (Sanofi Pasteur) for expert criticism and revision of the manuscript, and Frederick R. Vogel (Sanofi Pasteur) for coordinating the preparation of this manuscript. Medical writing was provided by Dr. Phillip Leventhal (4Clinics, Paris, France) and supported by Sanofi Pasteur.

Funding

The study was part of the Lyon BioPole MICROVAX research program and was funded by the French Ministry of Industry, Grenoble City Metro, Grand Lyon, and Rhône-Alpes region, as well as by Sanofi Pasteur. As the sponsor, Sanofi Pasteur was involved in all stages of the study conduct and analysis. Sanofi Pasteur also took in charge all costs associated with the development and the publishing of the present manuscript. The corresponding author had final responsibility to submit for publication.

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