Putnak et al (2005) Vaccine

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An evaluation of dengue type-2 inactivated, recombinant subunit, and liveattenuated vaccine candidates in the rhesus macaque model

J. Robert Putnaka, ‡, Beth-Ann Collerb, Gerald Vossc, David W. Vaughna, 1, David Clementsb, Iain Petersb, Gary Bignamib, Hou-Shu Hounga, Robert C.-M. Chena, David A. Barvira, Jitvimol Seriwatanaa, Sylvie Cayphasc, Nathalie Garçonc, Dirk Gheysenc, Niranjan Kanesa-thasana, 2, Mike McDonellb, 3, Tom Humphreysb, Kenneth H. Eckelsa, Jean-Paul Prieelsc and Bruce L. Innisa, d

(a) Walter Reed Army Institute of Research, Division of Communicable Diseases and Immunology, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA (b) Hawaii Biotech, Inc, 99-193 Aiea Heights Dr., Suite 200 Aiea, HI 96701, USA (c) GlaxoSmithKline Biologicals, Rue de l'Institut, 89, B-1330 Rixensart, Belgium (d) GlaxoSmithKline Pharmaceuticals, 1250 S. Collegeville Road, Collegeville, PA 19426, USA

Vaccine: Volume 23, Issue 35, 15 August 2005, Pages 4442-4452

Abstract The safety, immunogenicity, and protective efficacy of two non -replicating antigenbased vaccines and one live-attenuated virus (LAV) vaccine for dengue type-2 (dengue- 2) virus were evaluated in the rhesus macaque model. The non-replicating vaccines consisted of whole, purified inactivated vi rus (PIV) and a recombinant subunit protein containing the amino-(N)-terminal 80% of envelope protein (r80E), each formulated with one of five different adjuvants. Each formulation was administered to three animals on a 0, 3-month schedule. Follo wing the primary immuniza tions, 37 of 39 animals demonstrated dengue-2 virus neutralizing an tibodies. After the booster immunizations all animals had dengue neutralizing antibodies wi th peak titers ranging from 1:100 to 1:9700. The highest neutralizing antibody tite rs were observed in the groups that received r80E antigen formulated with AS04, AS05, or AS08 adjuvant, and PIV formulated with AS05 or AS08 adjuvant. T hese newer adjuvants are based on alum, fraction QS-21 of saponin, and monophosphoryl lipid A (MPL). Protection was evaluated by dengue-2 virus challenge 2 months afte r the booster by the measurement of circulating virus (viremia) and post-chal lenge immune responses. Several groups exhibited nearly complete protection against viremia by bioassay, although there was evidence for challenge virus replication by Taqman™ and immunological assays. None of the vaccines conferred sterile immunity.

The views expressed herein are those of the authors and should not be construed as official or to reflect the views of the Department of Defense or the U.S. Government.

‡ Corresponding author. Tel.: +1 301 319 9426; fax: +1 301 319 9661. 1 Present address: Medical Infectious Diseases Research Program, Ft. Detrick, Frederick, MD 21702 2 Present address: Acambis Inc., 38 Sidney Street, Cambridge, MA 02139 3 Present address: BresaGen, Inc., 111 Riverbend Road, Athens, GA 30605