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A canine parainfluenza viral vaccine: immunogenicity and safety.

A canine parainfluenza viral vaccine was developed and shown to be safe by absence of clinical disease in vaccinated dogs and by inability to isolate vaccine virus from blood or nasopharyngeal swabs. Backpassage in susceptible dogs, using blood of vaccinated dogs, could not be demonstrated. The vaccine produced neutralizing antibody when administered either intramuscularly or subcutaneously; however, a significantly higher immune response was obtained by intramuscular inoculation. Differences in the antibody response were not produced by tenfold dilutions of vaccine virus ranging from 10(2.9) to 10(5.9) median tissue culture infective doses. The presence of neutralizing antibody was associated significantly with decreased respiratory shedding period of challenge virus by vaccinated dogs compared to seronegative control dogs. Six days after aerosol exposure to virulent challenge virus, 100% of the controls (n = 5) but only 15% of the vaccinated dogs (n = 3) shed virus. Seven days after challenge exposure, virus could not be recovered from the vaccinated dogs, but 80% of the control dogs shed virus. An anamnestic response occurred in vaccinated dogs but not in the seronegative control dogs following challenge exposure. A mild clinical disease was produced in 3 of the 5 seronegative control dogs but not in the 20 vaccinated dogs.

Animals

The immunological response of calves after submucosal application of a live vaccine against parainfluenza-3- and adenovirus. (Brief report).

Using submucosal application of live attenuated vaccine against parainfluenza-3-virus and cattle adenovirus within the nasal opening, calves reacted with the formation of secretory (local) and serum antibodies of significantly higher titers than are received using subcutaneous application. The same vaccine induces interferon activity in the serum and nasal secretion after submucosal vaccination. Adenovirus antigen is a stronger interferon inducer than para-influenza-3-virus.

Adenoviridae

The assessment in sheep of an inactivated vaccine of parainfluenza 3 virus incorporating double stranded RNA (BRL 5907) as adjuvant.

The serological responses of conventionally reared sheep were compared after vaccination with inactivated parainfluenza 3 (PI3) virus incorporated in three different adjuvants. Inactivated PI3 virus with the double-stranded RNA, BRL 5907 in an oil emulsion was shown to stimulate higher serum antibody titres over the first 5 weeks after vaccination than virus with and without BCG emulsified in oil. The ability of this vaccine to protect specific pathogen-free lambs against challenge with PI3 virus was examined in a second experiment. In this experiment the vaccine stimulated virus neutralizing and haemagglutination inhibiting antibodies in the serum. After intranasal and intratracheal inoculation with PI3 virus at challenge, vaccinated lambs showed no clinical illness and virus isolation was confined, except in one lamb, to the first two days. In contrast, unvaccinated lambs developed respiratory disease and virus was isolated daily for 7 days after challenge.

Adjuvants, Immunologic

Vaccination against parainfluenza 1 virus (typus muris) infection in order to eradicate this virus in colonies of laboratory animals.

Parainfluenza 1 virus (typus muris), commonly known as Sendai virus, is still contaminating mouse colonies in Japan. This presents a serious problem to keep mouse colonies pathogen-free. It seems that the infection is spread by dust and the virus remains active a considerable time in the mouse breeding rooms after all mice are removed. In order to eradicate the infection of this virus, vaccination was attempted to inoculate newly born young mice successively for about six months and during and after these periods the movements of the infection were under observation. The vaccine used for this experiment was inactivated virus vaccine with mineral oil-Arlacel adjuvant. The induction of antibody level by the inoculation of this vaccine was evidenced to be very efficient and the duration of the immunity was also very satisfactory. However, after the cessation of the vaccination, the infection of the virus reappeared gradually after some period of temporary ease.

Animals

Live and killed virus vaccines: their use against the respiratory diseases of cattle.

The respiratory diseases of cattle are due to a combination of different factors among which figures a viral infection. The antiviral vaccination, perfectly possible owing to associated killed vaccines and live virus, is thus a very important element which must enter into every general plan of prophylaxis. Moreover, these plans will concern bacterial infections, conditions of rearing, etc. We have demonstrated that it is possible to produce good immunity in calves and sheep using a trivalent killed vaccine (parainfluenza 3, adenovirus 3 and reovirus 1). Possible interference with antibodies of maternal origin makes the multiplication of vaccine injections desirable.

Adenoviridae

Human parainfluenza virus 3 vaccine candidates attenuated by codon-pair deoptimization are immunogenic and protective in hamsters.

Human parainfluenza virus type 3 (HPIV3) is a major pediatric respiratory pathogen lacking available vaccines or antiviral drugs. We generated live-attenuated HPIV3 vaccine candidates by codon-pair deoptimization (CPD). HPIV3 open reading frames (ORFs) encoding the nucleoprotein (N), phosphoprotein (P), matrix (M), fusion (F), hemagglutinin-neuraminidase (HN), and polymerase (L) were modified singly or in combination to generate 12 viruses designated Min-N, Min-P, Min-M, Min-FHN, Min-L, Min-NP, Min-NPM, Min-NPL, Min-PM, Min-PFHN, Min-MFHN, and Min-PMFHN. CPD of N or L severely reduced growth in vitro and was not further evaluated. CPD of P or M was associated with increased and decreased interferon (IFN) response in vitro, respectively, but had little effect on virus replication. In Vero cells, CPD of F and HN delayed virus replication, but final titers were comparable to wild-type (wt) HPIV3. In human lung epithelial A549 cells, CPD F and HN induced a stronger IFN response, viral titers were reduced 100-fold, and the expression of F and HN proteins was significantly reduced without affecting N or P or the relative packaging of proteins into virions. Following intranasal infection in hamsters, replication in the nasal turbinates and lungs tended to be the most reduced for viruses bearing CPD F and HN, with maximum reductions of approximately 10-fold. Despite decreased in vivo replication (and lower expression of CPD F and HN in vitro), all viruses induced titers of serum HPIV3-neutralizing antibodies similar to wt and provided complete protection against HPIV3 challenge. In summary, CPD of HPIV3 yielded promising vaccine candidates suitable for further development.

Animals

An inactivated parainfluenza virus type 3 vaccine: the influence of vaccination regime on the response of calves and their subsequent resistance to challenge.

Calves maintained in insolated pens were vaccinated with an inactivated parainfluenza virus type (3) (pi3) vaccine usingparenteral and local route singly and in combination. The calves were subsequently monitored for serum antibody response and challenged intranasally with live virus to assess the protection derived from vaccination. Calves receiving one subcutaneous dose of vaccine in oil adjuvant produced a marked antibody response and were partially protected against challenge. Those receiving two successive subcutaneous doses produced a much greater antiboyd response and were completely protected against challenge. One intranasal dose of aqueous vaccine failed elicit a significant serum antibody response or protection against challenge. However, there was some evidence that intranasal vaccination following a single subcutaneous vaccination produced more effective immunity than one subcutaneous dose alone. Thus a vaccination regime was established which protected calves against experimental challenge and which could thefore be used in the field to assess the role of Pi3 virus in calf respiratory disease.

Administration, Intranasal

A comparison of immunologic response to intranasal and intramuscular parainfluenza-3 live virus vaccines in beef calves challenged experimentally in the feedlot.

Feeder calves were vaccinated with modified live virus (MLV) bovine parainfluenza-3 (PI-3) vaccines by the nasal and parenteral routes. Thirty days later they were challenged with the SF-4 strain of virus. Serum hemagglutination-inhibition (HI) antibodies and neutralizing antibodies in nasal secretions were compared with unvaccinated control calves. Both vaccines produced satisfactory circulating antibodies, but intranasal vaccination produced higher levels of antibodies in nasal secretions. After challenge PI-3 virus was not isolated from the vaccinated calves or two contact control unvaccinated calves but was isolated from all unvaccinated control calves isolated from vaccinated calves.

Administration, Intranasal

Immunity studies in calves vaccinated with a multivalent live respiratory vaccine composed of I.B.R., parainfluenza 3 and bovine adenovirus type 3.

The persistence of systemic and local antibodies was studied after two intranasal administrations of the vaccine, six weeks apart. Systemic antibodies to I.B.R. and adenovirus 3 evoked by the vaccine were still present 21 weeks following the second dose of the vaccine. Inconslusive results were obtained regarding the persistence of systemic and local PI-3 antibodies because of an intercurrent natureal PI-3 infection occurring during the observation period. Local antibodies to adenovirus type 3 were found in a high percentage of vaccinated animals 21 weeks after the second dose of the vaccine, whereas local antibodies to I.B.R. remained detectable in 50% of the animals eight weeks after thesecond dose. The results of a challenge study 21 weeks after revaccination show that the presence of local and systemic antibodies prevent the multiplication of PI-3 and BAV-3 in the upper respiratory tract. Protection against I.B.R. was achieved in the absence of detectable local antibodies.

Adenoviridae

The nasal secretion and serum antibody response of lambs following vaccination and aerosol challenge with parainfluenza 3 virus.

The nasal and serum neutralising antibody responses of lambs was compared following vaccination with live or inactivated parainfluenza 3 (PI 3) virus by either intramuscular (IM) or intranasal (IN) routes. Nasal antibody was only detected following inoculation of live virus IN or inactivated virus in Freund's complete adjuvant (FCA) IM. Immunity to aerosol challenge, as assessed by viral shedding from the nose, was conferred by (1) live virus administered by either route, (2) two IM inoculations of inactivated virus in FCA, and (3) one IM injection of inactivated virus in FCA followed by IN instillation of inactivated virus.

Administration, Intranasal

Immune response of cattle to intranasally or parenterally administered parainfluenza type 3 virus vaccines.

The principal significance of PI-3 virus in the bovine respiratory disease complex would seem to be its role in predisposing the respiratory tract to bacterial infection by (5) disrupting the integrity of the superficial mucosa and (3) producing a more favourable milieu for bacterial growth. Attention has therefore been given to establishing local immunity to preclude infection of superficial cells of the mucosa. Criteria used to evaluate the degree of such immunity are (5) presence of specific antibody activity in nasal secretions and (3) extent of virus excretion in nasal secretions following challenge with low passage virus. Studies completed thus far demonstrate that modified, live PI-3 virus administered intranasally is more effective than either modified, live or inactivated PI-3 virusadministered by parenteral injection in providing antibody activity in respiratory tractsecretions and in reducing virus excretion following challenge. IgA antibodies, presumably synthesized locally, apparently contribute heavily to the total antibody activity present in respiratory tract secretions.

Administration, Intranasal

[Interfering and interferonogenic activity of attenuated and original para-influenza viral strains].

A higher interfering activity of attenuated (vaccine) strains of parainfluenza virus types 1, 2 and 3 which had undergone a long-term adaptation to cell cultures as compared to the original viruses was established. The interferon-inducing activity of vaccine parainfluenza virus types 2 and 3 was also higher than that of the original viruses. The high interfering and interferon-inducing activity of attenuated parainfluenza virus strains of type 2 and 3 correlated with reduced virulence of these variants for man. These tests may be used for the assessment of virulence of parainfluenza virus strains type 2 and 3 in the laboratory.

Cells, Cultured

Immunoglobulins in the serum and nasal secretions of lambs following vaccination and aerosol challenge with parainfluenza 3 virus.

Serial changes in the concentrations of IgM, IgG and IgA were compared in specific pathogen free (SPF) lambs which had been vaccinated with live or inactivated parainfluenza 3 virus (PI 3) by either intramuscular (IM) or intranasal (IN) routes followed by aerosol challenge with PI 3. In the serum, an increase in IgM was associated with the primary antibody response to the aerosol challenge, whereas increased IgG was associated with the secondary antibody response. No changes in immunoglobulin concentrations were observed in the nasal secretions of lambs administered live or inactivated virus IM or IN without adjuvant. Marked increases in IgG were found in the serum and nasal secretions of lambs vaccinated IM with inactivated virus in Freund's complete adjuvant (FCA) and fractionation by gel filtration confirmed that the antibody was associated with IgG in both these fluids.

Administration, Intranasal

[Production of a polyglobulin preparation against respiratory diseases in calves].

On the basis of literature data concerning the production of polyglobulins from animal sera with the employment of appropriate, short term methods, and using the author's personal experience a method was tested for the production of specific polyglobulins against the respiratory complex in calves. A particular scheme was used for the purpose, hyperimmunizing adult cattle with killed vaccines against parainfluenza-3, adenoviruses 1 and 3, and IBR. The hyperimmune serum obtained was further treated by the etanol short term method to produce a high-titer polyglobulin. The preparation was tested in the field in the control of respiratory diseases in calves, showing very good prophylactic effects with an abrupt drop of the morbidity rate. In the case of disease outbreaks among treated animals these responded positively to an effective causal therapy. Thanks to its usability the method is recommended for the practice.

Animals

Immunoglobulins and their relative neutralizing efficiency in cattle immunized with infectious bovine rhinotracheitis--parainfluenza-3 (IBR-PI-3) virus vaccine.

The localization of anti-IBR and anti-PI-3 activity in the serum and nasal secretory immunoglobulins following intranasal immunization of cattle with a mixed vaccine (IBR-PI-3, MLV, TCO) was studied and was found to reside in the nasal secretory IgA, serum IgM and IgG fractions. The computation of their relative virus neutralizing efficiencies from kinetic data revealed their order of neutralizing efficiencies to be IgM greater than IgA greather than IgG.

Administration, Intranasal