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Bivalent influenza vaccination with inactivated vaccines administered by nasal or oral route.

Influenza vaccinations were performed either by administration of a bivalent A2 + B vaccine, or by successive application of monovalent B and A2 vaccines. During an influenza epidemic caused by an A2 strain, the following observations could be made: a) the best efficiency (no influenza cases) was recorded in adults and aged persons (over 65 years) irrespective of the vaccination scheme; b) in schoolchildren the best results (no influenza cases) were obtained in the lot having received monovalent A2 vaccine, and in the lot vaccinated nasally with monovalent B vaccine and 14 days later with monovalent A vaccine.

Administration, Intranasal

[Rabies vaccine inactivated with ethylenimine. Duration of the immunity in dogs].

The duration-of-immunity afforded by the ethylenimine inactivated rabies vaccine produced in BHK cells with the PV strain, was studied in dogs. One hundred per cent of the dogs became serologically positive 7 days after vaccination; the same percentage was still positive 3 years after vaccination with one dose of the vaccine. A good correlation was observed between the antibody profiles as determined by the titers obtained with the mouse neutralization and fluorescent field inhibition techniques. The correlation was not as good when the number of international units per ml was determined by both tests. The best correspondence between serological response and resistance to challenge was observed when the antibodies were determined by the number of international units per ml, using the neutralization test in mice. All the dogs challenged 12 and 25 months after vaccination resisted challenge; 89% (8/9) were protected 36 months after vaccination. Inactivated vaccines can be as effective to control rabies as those prepared with modified live virus; moreover, the inactivated vaccines are more stable and safer than the latter.

Animals

[Virus-neutralizing activity of colostral immunoglobulins in swine vaccinated with an inactivated vaccine against Aujeszky's disease virus].

Colostral globulins of sows immunized with an ethanol-saponin vaccine against Aujeszky's disease virus were fractionated through gel filtration by means of Sephadex-200. The virus-neutralizing activity of the globulin fractions identified through agar gel immunoelectrophoresis was evaluated by the virus-neutralizing test with cell cultures. The level of the antibodies found in class IgG substantially exceeded that of the IgA antibodies. It is believed that after muscular application of an ethanolsaponin vaccine against Aujeszky's disease the mammary gland of the vaccinated sows secretes virus-neutralizing antibodies mainly of the IgG class.

Animals

[Vaccination using an inactivated vaccine on a pig-breeding farm infected with the virus causing Aujeszky's disease (author's transl)].

When Aujeszky's disease was detected on a large pig-breeding farm, all normal sows and boars were vaccinated with an ethyl-ethylene-imine (EEI) vaccine produced in the Bundesforschungsanstalt für Viruskrankheiten der Tiere (Federal Research Institute for Viruses Diseases in Animals) in Tübbingen, Western Germany. The vaccine contained DEAE dextran as an adjuvant. The vaccine was inoculated twice by intramuscular route at a three weeks' interval, 5 ml. being inoculated at one time. Hyperimmune serum was inoculated in young pigs. In addition, hygienic procedures were adopted, consisting in disinfection and isolation. The disease was successfully controlled within eight weeks. Sows which developed Aujeszky's disease showed hardly any symptoms suggesting lesions of the central nervous system. Pulmonary lesions were the outstanding clinical feature. The semen quality of the affected male swine had markedly deteriorated. This was resorted to normal, however, within from five to ten weeks. The incidence of abortion and piglet mortality were low. In view of the results of virological and serological studies, it was concluded that the persistence of this strain of virus (causing Aujeszky's disease) was very slight.

Animals

Comparison of the protective efficacies of the live vaccine RIT 4025 and an inactivated vaccine against a natural heterologous A/Victoria/3/75 infection.

A clinical trial was initiated in South Africa before the winter season of 1976. The study involved 253 volunteers divided into three groups of vaccinees and one control group. Two groups of vaccinees were inoculated with either one or two doses at 2 weeks' interval (10(7.2) EID 50/dose) of the RIT 4025 live recombinant strain [A/Scotland/840/74 (H3N2) serotype] and one group received one injection of an inactivated vaccine [A/Port Chalmers/1/73 (H3N2), 360 i.u., A/Scotland/840/74 (H3N2), 300 i.u. and B/Hong Kong/8/73, 300 i.u./dose]. The serum antihaemagglutinin antibody responses against the heterologous A/Victoria/3/75 strain as measured by the single radial haemolysis test were satisfactory and not statistically different in all groups of vaccinees. On the other hand, the antineuraminidase antibody response was better in the group receiving the killed vaccine. At the end of the influenza season, A/Victoria/3/75 infections were confirmed serologically. Only 12% of the infections were symptomatic. The infection rate was significantly reduced in the live vaccine groups, whereas in the killed vaccine group the percentage of infection was lower but not significantly different from that in the placebo group.

Antibodies, Viral

Measles vaccination. VIII. The occurrence of antibodies against virus envelope components after immunization with inactivated vaccine. Effects of revaccination with live measles vaccine.

Children immunized with 4 doses of formalin-inactivated vaccine and/or purified hemagglutinin prepared from Tween 80-ether (TE) treated material were subjected to a follow-up 8-9 years after the last dose of vaccine. 11 out of 27 children had clinical and/or serological signs of infections with wild measles virus during the 8 to 9 years post-booster period. 10 out of the 11 children with infections had non-hemagglutinating-inhibiting (HI) hemolysis-inhibiting (HLI) antibodies demonstrable in their sera after removal of HI antibodies by absorption with TE antigen. In contrast 13 out of 16 vaccinees without detectable signs of infection lacked non-HI HLI antibodies. 10 out of these 13 children were vaccinated with further attenuated live measles virus. There were no clinical reactions to faccination. 4 vaccinees with low pre-vaccination HI antibody titers showed significant rises of antibody titers including non-HI HLI antibodies. In the remaining children no take of the live vaccine could be demonstrated. Thus HI antibodies of a certain minimal concentration can block the replication of vaccine virus even in the absence of non-HI HLI antibodies. However, since it will be difficult to establish these conditions by sue of available inactivated vaccines it is recommended that future vaccine products should include both major virus envelope surface components, the hemagglutinin and the hemolysin.

Antibodies, Viral

Development of inactivated vaccine for Akabane disease.

Virus inactivated by formalin or beta-propiolactone was superior to that inactivated by ether and heating in immunogenicity to mice. There were no significant differences in the antibody response of mice among such adjuvants as aluminum phosphate gel, aluminum hydroxide gel, and sodium arginate gel. When cattle were immunized with vaccine inactivated by formalin and adsorbed to aluminum phosphate gel, an excellent effect was obtained by injection with two doses of 3 ml each given at a 4-week interval. It was also suggested that mice and guinea pigs might be available for the potency test of vaccine. When calves and pregnant goats were injected with vaccine in the same manner as mentioned above, they were prevented from viremia and fetal infection caused by challenge virus. Even when stored at 4 degrees C for 12 months, vaccine was found to retain its stabilized immunogenicity. When pregnant cows were injected with vaccine in the field, the positive rate of neutralizing antibody was 88.5% in the 2 months after the first injection. When other pregnant cows were injected twice with vaccine, this rate was 34.6, 100, 65.4, and 45.8% in the 1, 2, 6, and 10 months, respectively, after the first injection. In another experiment, the antibody levels attained declined rather rapidly in several months. A single dose of vaccine given one year later provoked a rapid antibody response. The vaccination caused no clinical symptoms, abnormal birth, or decrease in milk yield in these cows.

Animals

[Immunogenic activity of cultural antirabies vaccine inactivated by gamma-rays].

Experimental lyophilized tissue culture rabies vaccine inactivated with gamma-rays was prepared from the Vnukovo-32 strain and showed a sufficiently high immunogenic activity. Complete inactivation of the virus and the immunogenic potency of the vaccine depended upon the dose of irradiation and temperature during irradiation. The virus lost infectivity at 18 degrees C when irradiated with 2.6 X 10(6) r and at --70 degrees C with 4.55 X 10(6) r. However, the immunogenic potency of the vaccine inactivated at minus temperature without thawing was significantly higher.

Animals

Immunization of mice and calves against Salmonella dublin with attenuated live and inactivated vaccines.

Previous findings, viz. that mice can be successfully immunized against infection with Salmonella dublin with either live or inactivated vaccine, were confirmed. Immunity lasted for at least 12 weeks in mice which had been immunized with inactivated alum-precipitated vaccine. The immunogenicity of inactivated vaccine gradually decreased on storage at 4 degrees C, but this was only detectable if a single injection was used for immunization: 2 injections virtually eliminated this phenomenon. The immunogenicity of live vaccine in mice was not enhanced by levamizole or the simultaneous injection of inactivated organisms. Both live and inactivated vaccines provided immunity in calves. A single injection of lyophilized vaccine, prepared from live rough Salmonella dublin strain (HB 1/17),protected 3 out of 6 calves, while 2 injections of a formalin-inactivated, alum-precipated vaccine, containing 1% packed cells of S. dublin strain 2652 V, protected 5 out of 6 calves against intraduodenal challenge with 2 x 10(9), S. dublin strain 2652 V. Two calves which had been immunized with an inactivated oil adjuvant vaccine were also solidly immune to this challenge. Serum antibody response in calves was poor when measured by the tube agglutination and the haemagglutination tests. Similarly, the sera had only marginal protective values when tested by means of a passive protection test in mice. Antibody titres alone are not a valid measure therefore, for the immune status of immunized animals.

Animals

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

Pre-clinical immunogenicity and safety evaluation of H2 strain Hepatitis A Inactivated Vaccine in rhesus macaques.

BACKGROUND: Hepatitis A is a viral infection of the liver that can cause mild to severe illness. Currently, two types of HAV vaccines are used worldwide, inactivated hepatitis A vaccines, which are used in most countries, and live attenuated vaccines (H2 and L-A-1 strain), which are mainly used in China. The major disadvantage of live attenuated virus to cause secondary infections among contacts and mutation shifts of the live vaccine strain. The H2 strain was selected for the development of an inactivated hepatitis A vaccine to further reduce biosafety risks. Rhesus macaques high genomic homology with humans and the incubation period after hepatitis A vaccination and human natural infections are similar. We use rhesus macaques to assess immunogenicity and safety of the H2 strain Hepatitis A Inactivated Vaccine. METHODS: The vaccine was assessed in rhesus macaques, divided into four groups (n = 10 per group): the control group (adjuvant buffer; aluminum content 0.35 mg/mL; 2 mL per dose), the low-dose group (320EU, 0.5 mL of 640EU/mL with aluminum content 0.35 mg/mL), the medium-dose group (640EU, 1 mL of 640EU/mL with aluminum content 0.35 mg/mL), and the high-dose group (1280EU, 2 mL of 640EU/mL with aluminum content 0.35 mg/mL). Animals were injected intramuscularly at multiple sites in the hind limbs and received four inoculations at 4-week intervals. Test items including Clinical indicators, immunogenicity indicators and Histopathological examination. RESULTS: No abnormalities were observed in any group in terms of general clinical condition throughout the study period except for slight decreases in body temperature after immunization. Hematological parameters, serum biochemistry indices, and histopathological findings showed fluctuated to different degrees of fluctuation after immunization across all groups. Immunogenicity assessments showed that the inactivated hepatitis A vaccine (H2) induced both humoral and cellular immune responses effectively, and the levels of antibodies increased with certain dose- and time-response trends. CONCLUSION: The inactivated hepatitis A vaccine (H2 strain, human diploid cell) was safe and immunogenic in non-human primates. The results provide strong preclinical support for the further clinical development of this vaccine candidate.

Animals

[Immunizing against salmonella infections with live and inactivated vaccines].

A live attenuated auxotrophic S. typhimurium (S. tm.)-mutant was used by orally administration via drinking water several times during rearing, combined with 1- or 2-times parenteral injection of an autogenous S. enteritidis (S. e.)/S. tm.-oil emulsion vaccine. In a 8-month period, more than 500,000 birds were vaccinated. The vaccine was safe. Challenge test showed protection in the vaccinates and their offspring. The number of isolates in the farms detected by regular monitoring decreased. The protection of the live-culture mutant lasted about only 8 to 10 weeks. A. S. tm.-mutant more potent for chickens will be tested now. We consider vaccinations as one important factor in a salmonella control program, especially for commercial layers and broiler breeders.

Animals

Viscerotropic velogenic Newcastle disease in turkeys: immune response following vaccination with either viable B1 strain or inactivated vaccine.

When used as a vaccine, live letogenic B1 Newcastle disease virus (NDV) protects turkeys against challenge-exposure to viscerotropic velogenic NDV (VVNDV). Low-level passively-immune poults were vaccinated one, two, or three times at various intervals and their immunity challenged at various times from 1 to 10 months of age. Newcastle disease virus was isolated readily from either the blood, trachea, or vent of turkeys in all challenge groups (through 5 months of age) on the 3rd to 6th days postchallenge (PC) but after 14 days PC was isolated rarely. Virus was isolated from turkeys that had high titers of serum hemagglutination-inhibition antibodies at the time of challenge. The anamnestic antibody response appeared to be stronger in poults that had low antibody titers prior to challenge-exposure to VVNDV. In a small-scale study with an inactivated VVNDV vaccine, vaccinated poults were protected against challenge with the homologous viscerotropic virus. Parallel control studies on the infectivity of viscerotropic NDV for turkeys indicated that resistance to VVNDV increased with age.

Administration, Oral

Immunization against human and swine-like influenza A: serological response to two inactivated vaccines of different formulation.

The immunizing capacity and the tolerability of two purified vaccines containing the inactivated A/New Jersey/76 ( x 53 recombinant) swine-like strain were studied. A trivalent vaccine (A/New Jersey/76-300 I.U.; A/Victoria 3/75-300 I.U.; B/Hong Kong 5/75-300 I.U.) was administered to 31 subjects over 50 years of age. No side-effects were observed and it caused a good HI antibody response to A/New Jersey/76, fairly good for B strain and modest for A/Victoria 3/75. A monovalent vaccine (A/New Jersey/76-400 I.U.) was administered to 32 subjects in the age range from 16 to 43 years. HI antibodies occurred in 84% of the subjects, devoid of antibodies before vaccination. Younger subjects (between 16-20 years) generally developed fairly low antibody titres; one among them (16-year-old) had a temperature rise within 48 h after vaccination. The Authors expect that the X 53 recombinant with the surface antigens of the A/New Jersey/76 strain may be employed for the preparation of the inactivated vaccine to be used in an emergency situation and discuss the composition of the vaccine more adapt for the present epidemiological situation.

Adolescent

Laboratory trials with inactivated vaccines against Escherichia coli (O2:K1) infection in fowls.

Laboratory trials were carried out with an O2:K1 vaccine prepared with either the Freund's complete or incomplete adjuvant. Both types of vaccine administered subcutaneously were highly effective against a challenge with the vaccine strain within three to four weeks after vaccination at two to three weeks of age. The complete adjuvant vaccine was more effective than the incomplete adjuvant vaccine when administered to chickens of an earlier age, and in the rate of development and duration of immunity. The efficacy of both vaccines was unimpaired by their incorporation with the Newcastle disease oil adjuvant (inactivated) vaccine (Newcadin). The use of an oil adjuvant vaccine was not found to affect the rate of growth adversely or to produce any other reaction prejudicial to its commerical application. The efficacy of the vaccines was unimpaired by their incorporation with Newcastle disease oil adjuvant (inactivated) vaccine (Newcadin) thus demonstrating the possibility of producing a combined Escherichia coli/Newcastle disease virus vaccine.

Age Factors

[Production and study of the immunogenic properties of a bivalent inactivated vaccine against mucosal disease (bovine viral diarrhea and infectious rhinotracheitis)].

Bivalent inactivated vaccine against mucous disease (MD) and infectious rhinotracheitis (IR) in cattle was produced from cell cultural MD and IR virus suspensions. The vaccine was concentrated on aluminium hydroxide, inactivated by ethanol and is without residual virus. Saponine in final 1:1500 dilution is added as supplementary adjuvant. Immunogeneity of the vaccine was tested on 10-month-old calves, which had shown full resistance against experimental infection with virulent strains of both viruses. Testing on calves for harmlessness by use of a five-fold higher vaccine dose indicated complete tolerance of the vaccine. The prophylactic effect of the vaccine applied in practical work to directly threatened with immediate MD and IR infection cows, including pregnant ones, consisted in reduced number of cases of abortion, of inborn malformations, in lower neonatal calf death-rate, etc. No disturbances were observed following two-fold vaccination of the animals, a fact proving its harmlessness. The positive results of the studied vaccine allow its further application in the combined prophylaxis of MD and IR in calf fattening and breeding complexes.

Animals