Fusion proteins comprising vasoactive intestinal peptide or PACA

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai

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514 12, 4353201, 435 697, 435325, 4352523, 530350, 536 234, A61K 3816, C12N 510, C12N 1562, C12N 1563

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active

060373210

DESCRIPTION:

BRIEF SUMMARY
This invention relates to vasoactive intestinal peptide ("VIP") and cross-reactive peptides. In particular, this invention relates to peptides capable of inducing antibodies which neutralize the activity of VIP. This invention also relates to tandemly repeated peptides derived from VIP or from cross-reactive peptides, which can elicit a broad immune response. The present invention is useful for increasing egg production in bird species and for increasing efficiency of feed utilization and rate of gain in food producing animals.


BACKGROUND OF THE INVENTION

VIP has been proven to be a potent releaser of avian prolactin ("PRL") in vivo and in vitro. Prolactin is a hormone produced by the anterior pituitary and it is well established that prolactin can initiate incubation behaviour in birds such as turkeys, bantam hens and many species of wild birds.
Incubation behaviour leads to early cessation of egg laying and has a fundamental role in avian reproduction. The incubation behaviour has been of great interest to scientists and producers of hatching eggs and of particular interest in the field of turkey breeding since reproductive efficiency of turkey hens is low in comparison with chickens. This low efficiency has been associated with incubation behaviour and there is convincing evidence that increased PRL secretion causes reduction in circulating gonadotropins, ovarian regression, and the shift from the egg laying to the incubation phase of the reproductive cycle in the turkey.
Incubation behaviour may be suppressed by blocking the biological effect of VIP on prolactin induction. Passive immunization of incubating chickens with anti-VIP serum has been found to induce a reduction in plasma PRL and pituitary PRL mRNA, resulting in termination of incubation behaviour. Active immunization of female turkeys with chicken VIP has also been reported to suppress circulating PRL and inhibit the expression of incubation behaviour resulting in a substantial increase in egg production. Therefore, active and passive immunization against VIP may be useful for modifying the egg-laying performance of avian species. Among the desired effects are that hens lay eggs for a longer period of time, that there is an increase in the number of eggs laid, and that non-laying hens commence laying eggs.
Further, VIP was initially identified for its vasoactive properties in mammals. VIP causes relaxation of isolated gastric and intestinal smooth muscle cells. VIP-induced relaxation is mediated by high-affinity VIP receptors and can be inhibited by VIP antiserum and selective VIP antagonists.
Critical affected segments of the gastrointestinal tract occur at the pyloric-duodenal junction, the junction between the small intestine and the large intestine, and the anal sphincter. Immunization of food-producing animals against VIP may result in increased tone of these segments leading to increased efficacy of absorption of food with a consequent increased rate of feed efficiency and rate of weight gain.
Immunization against VIP presently entails chemically synthesizing the full length of VIP and conjugating the resulting peptide to a carrier molecule. Commercial application of this non-recombinant technique is expensive and difficult, and moreover conjugation of the VIP with a carrier molecule is highly unpredictable, therefore resulting in low yields of useful antigenic proteins. Further, this technique would require, firstly, a ready source of VIP antigens and, further, antigens which can elicit a broad immune response. These immunogens are not currently available. Thus, it is desirable to develop a recombinant system whereby antigenic fusion proteins are made and the conjugation step is avoided.


SUMMARY OF THE INVENTION

Accordingly, the present invention relates to a nucleotide sequence comprising (1) a DNA sequence coding for at least one copy of vasoactive intestinal peptide, and/or at least one copy of a cross-reactive protein, and/or at least one copy of a peptide fragment derived from vasoactive intestinal peptide and/or a cross-re

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