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PubMed2005

Recombinant newcastle disease virus expressing a foreign viral antigen is attenuated and highly immunogenic in primates.

Paramyxoviruses such as human parainfluenza viruses that bear inserts encoding protective antigens of heterologous viruses can induce an effective immunity against the heterologous viruses in experimental animals. However, vectors based on common human pathogens would be expected to be restricted in replication in the adult human population due to high seroprevalence, an effect that would reduce vector immunogenicity. To address this issue, we evaluated Newcastle disease virus (NDV), an avian paramyxovirus that is serotypically distinct from common human pathogens, as a vaccine vector. Two strains were evaluated: the attenuated vaccine strain LaSota (NDV-LS) that replicates mostly in the chicken respiratory tract and the Beaudette C (NDV-BC) strain of intermediate virulence that produces mild systemic infection in chickens. A recombinant version of each virus was modified by the insertion, between the P and M genes, of a gene cassette encoding the human parainfluenza virus type 3 (HPIV3) hemagglutinin-neuraminidase (HN) protein, a test antigen with considerable historic data. The recombinant viruses were administered to African green monkeys (NDV-BC and NDV-LS) and rhesus monkeys (NDV-BC only) by combined intranasal and intratracheal routes at a dose of 10(6.5) PFU per site, with a second equivalent dose administered 28 days later. Little or no virus shedding was detected in nose-throat swabs or tracheal lavages following immunization with either strain. In a separate experiment, direct examination of lung tissue confirmed a highly attenuated, restricted pattern of replication by parental NDV-BC. The serum antibody response to the foreign HN protein induced by the first immunization with either NDV vector was somewhat less than that observed following a wild-type HPIV3 infection; however, the titer following the second dose exceeded that observed with HPIV3 infection, even though HPIV3 replicates much more efficiently than NDV in these animals. NDV appears to be a promising vector for the development of vaccines for humans; one application would be in controlling localized outbreaks of emerging pathogens.

Administration, Intranasal↗
PubMed1978

[Comparative studies of methods for the detection of immune carriers of the Newcastle disease virus in poultry].

Mass prophylactic vaccinations have radically chaugned the clinical syndrome, pathogenesis, and morphological picture of the Newcastle disease: clinically it is manifested with respiratory troubles, and morphologically--with tracheitis. The method for isolating the virus on chick embryos from immune birds have proved undependable: the higher the immunity of birds, the lower the probability of virus isolation. Following the vaccination of birds after the adopted prophylactic programme and at the three-fold vaccination with a lentogenic La Sota strain and four-fold vaccination with a mesogenic Komarov strain precipitating antibodies have been detected in single serum samples only. In the presence of respiratory troubles in immune birds the rise of antiheamagglutination titers and the mass manifestation of precipitating antibodies in the blood serum is said to be an indication of the presence of a field of velogenic virus, while HI and AGPT are suitable methods for the detection of immune carriers of Newcastle disease. These can be used also for the differential diagnosis of the latent forms of infectious bronchitis, infectious laryngotracheitis, the diphtheroid form of pox, and CRD. In order to restrict and do away with the velogenic field strains of the Newcastle disease virus a suggestion is made to kill all birds that have shown respiratory troubles and positive results in virologic and serologic examinations through HI and AGPT.

Animals↗
PubMed2001

PACT, a double-stranded RNA binding protein acts as a positive regulator for type I interferon gene induced by Newcastle disease virus.

Virus infection triggers innate responses to host cells including production of type I interferon (IFN). Since IFN production is also induced by treatment with poly(I:C), viral double-stranded (ds) RNA has been postulated to play a direct role in the process. In the present study, we investigated the effect of dsRNA binding proteins on virus-induced activation of the IFN-beta gene. We found that PACT, originally identified as protein activator for dsRNA-dependent protein kinase (PKR) and implicated in the regulation of translation, augmented IFN-beta gene activation induced by Newcastle disease virus. Concomitantly with the augmented activity of IFN-beta enhancer, increased activity of NF-kappaB and IRF-3 and IRF-7 was observed. For the observed effect, the dsRNA-binding activity of PACT was essential. We identified residues of PACT that interact with a presumptive target molecule to exert its function. Furthermore, PACT colocalized with viral replication complex in the infected cells. Thus the observed effect of PACT is novel and PACT is involved in the regulation of viral replication and results in a marked increase of cellular IFN-beta gene expression.

Amino Acid Sequence↗
PubMed1979

Effect of feeding 1,3-butanediol-1,3-dioctanoate as an energy source for chicks for catch-up growth during recovery from Newcastle disease virus.

1,3-Butanediol-1,3-dioctanoate (BDDO), a synthetic source of energy, has been shown to be equal to corn oil when fed to chicks recovering from moderate and severe Newcastle disease virus infections. Body weight increments of chicks fed diets containing 10% BDDO were equal to or greater than those of chicks fed 10% corn oil, both with restricted feeding regimens. Kilocalories of metabolizable energy required to produce 100 g of body weight increment over a basal group was used as a means of quantitating energy demand. BDDO was comparable to corn oil as an energy source with no adverse effects. Liver/body weight ratios were greater in the BDDO-fed chicks. Circadian rhythmicity of liver size and liver glycogen content was demonstrated. Chicks fed BDDO had total liver glycogen content threefold that of the corn oil controls, which was attributed to stimulation of insulin secretion. Catch-up growth in the chick following the growth depression of disease appears to be as well facilitated by a synthetic source as by a natural one.

Animals↗
PubMed1978

[Retention of the Newcastle disease virus in immunized poultry].

The period of virus harbouring was followed up in a total of 50 experimentally infected (Newcastle disease) birds. Two methodes were used to isolate the challenging virus: the ordinary virologic procedures and the method of tissue cultures. Studied was also the effect of the humoral immunity on the persistence of the virus. Investigations by the tissue culture method revealed a persisting latent infection in the course of 70 day, which in certain cases could assume an acute course and become apparent. The Newcastle disease virus was isolated from birds having either low or very high levels of serum agglutinins. The currently employed virologic methods failed to demonstrate the virus after the 16th day of infection.

Animals↗
PubMedDate not supplied

Effect of social stress on Newcastle disease virus (LaSota) infection.

Individual immature chickens were socially stressed when placed into an established group of chickens. The stress response was determined by periodic measurement of plasma cortisol and by determination of the relative regression of the bursa of Fabricius. Stressed chickens had elevated cortisol levels during the first 24 hours following the initiation of social stress. The bursa-to-body-weight ratios of stressed birds at 96 hours following stress were significantly lower than the ratios in control birds, and their tuberculin reaction was significantly depressed. Newcastle disease virus was more invasive and attained higher titers in stressed birds. The hemagglutination-inhibition (HI) response of the stressed birds was higher in one trial and lower in another.

Animals↗
PubMed1992

Active specific immunotherapy with Newcastle-disease-virus-modified autologous tumor cells following resection of liver metastases in colorectal cancer. First evaluation of clinical response of a phase II-trial.

A group of 23 colorectal cancer patients were treated by a new type of active specific immunotherapy (ASI) following complete surgical resection of liver metastases (RO resection). For ASI treatment we used a vaccine consisting of 1 x 10(7) autologous, irradiated (200 Gy) metastases-derived tumor cells incubated with 32 hemagglutination units (HU) of Newcastle disease virus (NDV). The adjuvant vaccine therapy was started 2 weeks after surgery and was repeated five times at 14-days intervals followed by one boost 3 months later. The delayed-type hypersensitivity (DTH) skin reactions to the vaccine were measured as well as the DTH reactions to a challenge test of 1 x 10(7) non-virus-modified autologous tumor cells from liver metastases or 1 x 10(7) autologous normal liver cells. In addition 32 HU NDV alone and a standard antigen test (Merieux test) were applied pre- and post-vaccination. The vaccination was well tolerated. In 13 of 23 patients an increasing reactivity against the vaccine was observed during the vaccination procedure. Nine patients (40%) experienced an increased DTH reactivity against autologous tumor cells following vaccination, while 17% or fewer showed an increased reactivity to Merieux test antigens, NDV, or normal liver cells. The increased antitumor response was not correlated to responsiveness to NDV alone, autologous liver cells, enzymes and culture medium used for vaccine preparation or standard antigens (Merieux test). After a follow-up of at least 18 months 61% of the vaccinated patients developed tumor recurrence in comparison to 87% of a matched control groups from the same institution that had been only surgically treated. The results of this phase II trial are encouraging and should stimulate further prospective randomized studies.

Adult↗
PubMed1976

Antibodies in blood and secretions of chickens immunized parenterally and locally with killed Newcastle disease virus vaccine.

In mammals the antibody activity in secretions is associated with the secretory IgA. This unique immunoglobulin plays a major role in immunity against infectious diseases of the alimentary and the respiratory tracts. We found a similar system of local immunity against Newcastle disease virus (NDV) in the fowl. Airway washings and bile globulins of chickens were examined by immunodiffusion and immunoelectrophoretic methods. No antigenic differences were found between the serum IgA and the secretory IgA of airway washings and of bile. The chicken IgA differs from mammalian IgA by lacking secretory component. Antibodies in the airway washings and in tears of chickens immunized by aerosol ir i.m. NDV vaccine (attenuated or inactive) were compared to serum antibodies produced by similar methods of administration. HI antibodies in secretions reached higher levels after aerosol vaccination than after i.m. administration, whereas in serum the situation was reversed. The antibody activity in airway washings and in tears is associated with IgA, while in serum the main antibody is IgG.

Aerosols↗