Vaccine 32 (2014) 11–18 Contents lists available at ScienceDirect Vaccine journal homepage: www.elsevier.com/locate/vaccine Computational designing of a poly-epitope fecundity vaccine for multiple species of livestock Bhaskar Ganguly a,∗ , Sunil Kumar Rastogi a , Shiv Prasad b a Animal Biotechnology Center, Department of Veterinary Physiology and Biochemistry, College of Veterinary and Animal Sciences, G. B. Pant University of Agriculture and Technology, Pantnagar 263145, Uttarakhand, India b Department of Animal Reproduction, Gynecology and Obstetrics, College of Veterinary and Animal Sciences, G. B. Pant University of Agriculture and Technology, Pantnagar 263145, Uttarakhand, India article info Article history: Received 16 August 2013 Received in revised form 19 October 2013 Accepted 24 October 2013 Available online 6 November 2013 Keywords: Agretope B-cell Epitope Follistatin Fecundity Helper T-cell Inhibin Peptide Vaccine Veterinary abstract Inhibin and follistatin are known to reduce fecundity by inhibiting the actions of activin and FSH. Thus, the immunoneutralization of these hormones is a rational proposal for augmenting reproductive per- formance. The present study describes a comprehensive computational methodology comprising of a consensus approach of several B- and T h -cell epitope prediction tools for the identification of epitopic regions within the structure of these hormones that can be incorporated into a poly-epitope fecun- dity vaccine. The proposed peptide (RGD-WSPAALRLLQRPPEEPA-KK-YSFPISSILE) should be effective in multiple animal species, generating good immunological memory. © 2013 Elsevier Ltd. All rights reserved. 1. Introduction Several approaches have been directed towards improving fecundity in livestock. One particular approach in this direction has been that of fecundity vaccines, which target hormones inhibitory to reproductive processes. Inhibin and follistatin are two major hormones that are responsible for inhibiting the release of Follicle Stimulating Hormone (FSH) and, hence, responsible for reducing fecundity [1–5]. Inhibin and activin are structurally related and are members of the Transforming Growth Factor- (TGF-) super- family [6]. Inhibin is a heterodimeric, glycoprotein (M r ∼32,000) consisting of two subunits alpha () and beta () linked by a single disulphide bond. The  subunit has two forms -A and -B, and the corresponding inhibin dimers are called inhibin-A and inhibin-B, respectively (Supplementary File 1). Each subunit represents the ∗ Corresponding author at: C/o Late Sri Bisweswar Gangopadhyay, D-04, Alliance Kingston Estate, Rudrapur-263153, Uttarakhand, India. Tel.: +91 9411159689; fax: +91 5944233473. E-mail address: vetbhaskar@gmail.com (B. Ganguly). carboxy terminus of a separate precursor molecule, processed by proteolytic cleavage at paired arginine residues to yield the mature forms [7]. The major source of inhibin is the granulosa cells of the ovarian follicles (Supplementary File 2). At low concentrations inhibin suppresses FSH synthesis, while at higher concentrations the pituitary content of both FSH and Luteinizing Hormone (LH) is reduced [3]. Specifically, inhibin acts by antagonizing activin signaling. Activin (M r ∼25,000) is a disulphide-linked dimer of two inhibin  subunits which stimulates pituitary FSH release and FSH mRNA accumulation [7]. Activin exerts its function by signaling through hetero-tetrameric complexes composed of activin-type II receptors (ActRII or ActRIIB); while the symmetrical structure of activin allows it to form complete hetero-tetrameric receptor com- plexes, the asymmetrical structure of inhibin allows it to only bind to the ActRII/IIB components, resulting in competitive inhibition [8]. Follistatin is a monomeric, cysteine-rich glycoprotein (M r ∼31,000–49,000; based on alternative mRNA splicing and variable glycosylation), which although structurally unrelated to inhibin suppresses pituitary FSH release in a manner similar to inhibin. Fol- listatin also binds activin at its  subunit to neutralize its bioactivity 0264-410X/$ – see front matter © 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.vaccine.2013.10.086