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Vaccine 28 (2010) 3025–3029Contents lists available at ScienceDirectVaccinejournal homepage: www.elsevier.com/locate/vaccineA phase I evaluation of inactivated influenza A/H5N1 vaccine administered by theintradermal or the intramuscular route?Shital M. Patel∗, Robert L. Atmar, Hana M. El Sahly, Thomas R. Cate, Wendy A. KeitelBaylor College of Medicine, Medicine – Infectious Diseases, BCM MS 280, One Baylor Plaza, Houston, TX 77030, United Statesa r t i c l ei n f oArticle history:Received 30 October 2008Received in revised form 28 October 2009Accepted 30 October 2009Available online 18 November 2009Keywords:Intradermal vaccinationPandemic influenzaH5N1 vaccinea b s t r a c tIn a phase I clinical trial, one hundred healthy young adults were randomized to receive two doses 28daysapartofaninactivated,subvirionvaccinecontaining15or45?gofinfluenzaA/H5N1hemagglutinin(HA) by the intramuscular (IM) route, or 3 or 9?g of H5 HA by the intradermal(ID) route. Seventy-sevensubjects received a third dose. All regimens were safe and well tolerated. Antibody responses after twoor three doses were low (≤20% or ≤38%, respectively) and similar in groups given 3 or 9?g ID or 15?gIM, and were significantly lower than those given 45?g IM. Higher dosages of H5 HA and/or inclusion ofadjuvant will be required to enhance immunogenicity by the ID route.© 2009 Elsevier Ltd. All rights reserved.1. IntroductionInfluenzavirusA/H5N1infectionswerefirstrecognizedtocauseinfections in humans in Hong Kong in 1997. Since 2003, theseviruses have become endemic among the poultry population inmanycountries.Morethan350laboratory-confirmedhumancasesof avian influenza A/H5N1 have been reported from 14 countriesto the WHO since 2003, and the case fatality rate has exceeded60% [1]. The emergence of influenza A/H5N1 viruses has raisedconcerns of a potential influenza pandemic, bolstering efforts todevelop immunogenic vaccines against influenza A/H5N1 viruses.Recent clinical trials have shown that standard dosages (15?g ofhemagglutinin, or HA) of subunit vaccines are poorly immuno-genic [2–4]. Although high dosages of HA (90?g) elicit detectableimmune responses in the majority of subjects, there are concernsthat current manufacturing capacity will not be sufficient to pro-duce adequate amounts of vaccine in the setting of a pandemic.Intradermal immunization (ID) is a potential dosage-sparingapproach being explored as a possible pandemic influenza vaccinestrategy. Several recent studies have evaluated ID administrationof interpandemic influenza vaccine with reduced dosages [5–10].Some of the studies report a potential advantage of ID comparedto IM immunization, but it is unknown whether these observations?Presented in part the VIII International Symposium for Respiratory Viral Infec-tions, Big Island, Hawaii, May 16–19, 2006 (oral presentation) and the 44th AnnualIDSA Meeting, Toronto, Ontario, Canada, October 12–15, 2006, late breaker presen-tation LB-5.∗Corresponding author. Tel.: +1 713 798 3793; fax: +1 713 798 6802.E-mail address: shitalp@bcm.edu (S.M. Patel).would hold true after ID administration of a potential pandemicinfluenza A vaccine in unprimed (no preexisting immunity) indi-viduals. In order to address this question, we conducted a phaseI evaluation of ID administration with a monovalent, subvirion,inactivated influenza A/H5N1 virus vaccine.2. Materials and methods2.1. Study designThis study was a single-center, phase I, randomized, open-label,dose-ranging, clinical trial. The study was initiated after the oneweek safety data of one dose of 15 and 45?g IM of the same inves-tigational vaccine was evaluated in a larger dose-ranging clinicaltrial [4]. The primary objectives of this study were to evaluate thedose-related safety, reactogenicity, and immunogenicity after twodoses of a monovalent, subvirion, inactivated influenza A/H5N1virus vaccine administered either by the intradermal (ID) or theintramuscular (IM) route to healthy young adults. The secondaryobjectives were to evaluate the dose-related immunogenicity ofthe vaccine at 1 and 7 months after the first dose and to assessthe safety, reactogenicity, and immunogenicity after a third doseof vaccine administered approximately 7 months after the seconddose.2.2. SubjectsDuringJuly2005,eligiblehealthy18–40-year-oldmenandnon-pregnant women were enrolled after providing written informedconsent. Enrollment criteria for the young adults were similar to0264-410X/$ – see front matter © 2009 Elsevier Ltd. All rights reserved.doi:10.1016/j.vaccine.2009.10.152