Vaccine 24 (2006) 5481–5490 A novel recombinant virus-like particle vaccine for prevention of porcine parvovirus-induced reproductive failure Adriaan F.G. Antonis a , Christianne J.M. Bruschke a , Paloma Rueda b , Luis Maranga c,1 , J. Ignacio Casal b,2 , Carmen Vela b , Luuk A. Th. Hilgers d , Peter B.G.M. Belt a , Klaas Weerdmeester a , Manuel J.T. Carrondo c , Jan P.M. Langeveld a,∗,3 a Animal Sciences Group (ASG, Previously ID-Lelystad), P.O. Box 65, 8200 AB Lelystad, The Netherlands b Inmunologia y Genetica Aplicada S.A. (INGENASA), Hnos. Garc´ ıa Noblejas 41, 4 0 , 28037 Madrid, Spain c Instituto de Biologia Experimental e Technol´ ogica (IBET), Apartado 12, 2780 Oeiras, Portugal d CoVaccine BV, Mauritsstraat 15, 3583 HE, Utrecht, The Netherlands Received 6 December 2005; received in revised form 24 March 2006; accepted 28 March 2006 Available online 18 April 2006 Abstract A novel vaccine against porcine parvovirus (PPV), composed of recombinant virus-like particles (PPV-VLPs) produced with the baculovirus expression vector system (BEVS) at industrial scale, was tested for its immunogenicity and protective potency. A formulation of submicrogram amounts of PPV-VLPs in a water-in-mineral oil adjuvant evoked high serum antibody titres in both guinea pigs, used as reference model, and target species, pigs. A single immunisation with 0.7 g of this antigen yielded complete foetal protection against PPV infection after challenge with a virulent strain of this virus. Furthermore, also in the presence of mild adjuvants the protective action of these PPV-VLPs is excellent. This recombinant subunit vaccine overcomes some of the drawbacks of classical PPV vaccines. © 2006 Elsevier Ltd. All rights reserved. Keywords: Porcine parvovirus; Virus-like particles; Vaccine; Recombinant 1. Introduction Porcine parvovirus (PPV) is an autonomously replicat- ing member of the feline parvovirus subgroup of the genus parvovirus within the family Parvoviridae [1,2]. Parvoviruses have a single-stranded DNA genome encapsidated by an non- enveloped icosahedral particle of 25 nm in diameter that is composed of three structural proteins: VP1, VP2 and VP3, of which VP2 is the major component [3]. ∗ Corresponding author. Tel.: +31 320 237217; fax: +31 320 238153. E-mail address: jan.langeveld@wur.nl (J.P.M. Langeveld). 1 Present address: Fermentation and Cell Culture, Bioprocess R&D, Merck & Co. Inc., P.O. Box 4 WP17-201, West Point, PA 19486, USA. 2 Present address: Centro Nacional de Investigaciones Oncol´ ogicas (CNIO), C/Melchor Fern´ andez Almagro 3, 28029 Madrid, Spain. 3 Present address: Central Institute for Animal Disease Control (CIDC- Lelystad), Edelhertweg 15, 8219 PH Lelystad, The Netherlands. PPV is an extremely durable and highly infectious virus. One of the major consequences of PPV infection in swine is reproductive failure, characterised by foetal death and mum- mification [4,5], in addition to its role in porcine respiratory disease complex [6], and post-weaning multi-systemic wast- ing syndrome [7,8]. When susceptible adult pigs are exposed to PPV at mating or during gestation, the virus readily crosses the placental barrier and infects the embryos or foetuses. Lit- ters infected with PPV may have variable numbers of affected foetuses due to intrauterine spread of the virus between foe- tuses [9]. The stage of gestation at the time of a PPV infec- tion mainly determines the resulting clinical manifestations. When transplacental infection of PPV occurs before 35 days of gestation, resorption of some or all foetuses takes place, resulting in a reduction of the litter size or return to service. If an infection occurs between day 35 and day 70 of gestation, one or more foetuses may die and mummificate. Infections 0264-410X/$ – see front matter © 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2006.03.089