Showing papers on "Viral Vaccine published in 1987"

Induction of protective immunity against rabies by immunization with rabies virus ribonucleoprotein

Abstract: We have studied the ability of rabies virus ribonucleoprotein (RNP) to induce a protective immune response in animals against lethal challenge with rabies and rabies-related lyssa viruses. Liposomes containing either RNP or the glycoprotein (G protein) of a variant virus with multiple alterations in the G antigenic structure conferred no or poor protection, respectively, against lethal intracerebral challenge with rabies virus. By contrast, liposomes containing RNP and the variant G protein induced a good protective response, comparable to that achieved with inactivated virus vaccine against intracerebral challenge. Moreover, mice or raccoons immunized with RNP alone resisted lethal peripheral challenge with homologous or heterologous virus strains. These results indicate that the RNP of rabies virus plays a crucial role in induction of protective immunity.

Immunization with a live attenuated dengue-2-virus candidate vaccine (16681-PDK 53): clinical, immunological and biological responses in adult volunteers.

Abstract: A live dengue-2 (DEN-2) candidate vaccine (strain 16681-PDK 53), attenuated by passage in primary dog kidney cells, was tested in ten adult volunteers for evaluation of the safety, infectivity and immunogenicity of a dose of 1.9-2.7 x 10(4) plaque-forming units. Five of the volunteers were nonimmune to either dengue or Japanese encephalitis (JE) viruses; the other five were nonimmune to dengue but immune to JE. After receiving 1.0 ml of the vaccine subcutaneously, all ten volunteers developed neutralizing antibodies to DEN-2 which were maintained for at least one and a half years. None of the subjects developed abnormal signs or symptoms and the results of clinical chemistry investigations were within normal range throughout the 21 days of observation after the immunization. Virus isolated from one viraemic volunteer retained the small-plaque and temperature-sensitive growth characteristics of the vaccine virus in vitro. Further testing of this candidate vaccine in humans is indicated.

Protection against respiratory disease in calves induced by vaccines containing respiratory syncytial virus, parainfluenza type 3 virus, Mycoplasma bovis and M dispar.

Abstract: A field trial to assess the ability of two vaccines to protect calves against respiratory disease was carried out on a large beef rearing unit in southern England over the two winters of 1983 to 1984 and 1984 to 1985. A quadrivalent vaccine containing the killed antigens of respiratory syncytial virus, parainfluenza virus type 3, Mycoplasma bovis and M dispar or a vaccine containing only the respiratory syncytial virus component were inoculated into 246 and 245 calves, respectively; 245 calves remained as unvaccinated controls. The calves were reared in seven batches and outbreaks of disease occurred in five; significant protection was achieved in the four batches in which disease was associated with respiratory syncytial virus and M bovis infection, together or independently. The death rate from pneumonia was 9 per cent in the control group, 2 per cent in the calves inoculated with the quadrivalent vaccine (P less than 0.001), a protection rate of 77 per cent, and 3 per cent in the calves inoculated with the respiratory syncytial virus vaccine (P less than 0.01), a protection rate of 68 per cent. The proportion of calves receiving treatment for respiratory disease was 38 per cent in the control group, 25 per cent in the calves inoculated with the quadrivalent vaccine (P less than 0.001) and 27 per cent in the calves inoculated with the respiratory syncytial virus vaccine (P less than 0.01). The results show that protection against respiratory disease can be achieved by parenteral vaccination of calves with the appropriate inactivated microorganisms.

Serological responses in chimpanzees inoculated with human immunodeficiency virus glycoprotein (gp120) subunit vaccine.

Abstract: The major envelope glycoprotein of a human immunodeficiency virus (HIV) has been purified and was utilized as a prototype vaccine in chimpanzees. The 120,000-dalton glycoprotein (gp120) was purified from membranes of human T-lymphotropic virus (HTLV)-IIIB-infected cells and the final preparation contained low levels to no detectable HTLV-IIIB core antigen (p24) and low levels of endotoxin. Chimpanzees inoculated with gp120 responded by developing antibodies that precipitated radiolabeled gp120 and neutralized in vitro infection of HTLV-IIIB. Antibodies to HTLV-IIIB p24 were not detected in the gp120-immunized chimpanzees. Peripheral blood leukocytes from the vaccinated animals were examined for T4+ and T8+ cells, and no decrease in the T4/T8 ratio was found, indicating that immunization with a ligand (gp120) that binds to T4 has no detectable adverse effect on the population of T4+ cells. The only current animal model that can be reproducibly infected with HIV is the chimpanzee. Immunization of chimpanzees with HIV proteins will provide an experimental system for testing the effectiveness of prototype vaccines for preventing HIV infection in vivo.

New serotype 2 and attenuated serotype 1 Marek's disease vaccine viruses: selected biological and molecular characteristics.

Abstract: Two new Marek's disease vaccine viruses, Md11/75C/R2 (serotype 1) and 301B/1 (serotype 2), were evaluated in chickens with maternal antibodies (ab+) or without maternal antibodies (ab-). Strain Md11/75C/R2 was mildly pathogenic in ab--chickens, but this pathogenicity was markedly reduced in ab+ chickens. Md11/75C/R2 spread less by contact and replicated better, both in vivo and in vitro, than CVI988/C, another serotype 1 vaccine virus. Strain 301B/1 was similar to SB-1, another serotype 2 vaccine virus: both were nonpathogenic for ab--chickens, spread readily by contact, and replicated well in vivo. In vitro, 301B/1 grew more rapidly and produced larger plaques than SB-1. Notable characteristics of strain CVI988/C included absence of pathogenicity, poor replicative ability, and the absence of one epitope detected by a common serotype-1-specific monoclonal antibody. All four viruses could be distinguished from each other by restriction enzyme analysis of viral DNA. We conclude that Md11/75C/R2, although exceptionally protective, may require further attenuation. On the other hand, 301B/1, which in other studies induced higher levels of protection than SB-1, is nonpathogenic and may be considered for use as a commercial vaccine.

Detection of asymptomatic herpes simplex virus infections after vaccination.

Abstract: Twenty-two volunteers seronegative for antibodies to herpes simplex virus (HSV) were enrolled in a trial to determine tolerance and immunogenicity of an HSV-2 glycoprotein subunit vaccine. Vaccine was administered at days 0, 28, and 140, and sera were obtained on days 0, 7, 14, 21, 28, 35, 49, 56, 140, 147, and 365 for determination of HSV neutralizing antibody activity and antibody-dependent cell cytotoxicity (ADCC). Sera were also tested by immunoprecipitation of radiolabeled HSV-2-infected cell proteins and polyacrylamide gel electrophoresis to identify the viral proteins which elicited antibody responses in vaccine recipients. After vaccination two male volunteers presented with atypical first-episode genital herpes: patient 1 with a culture-negative genital lesion at day 53 and patient 3 with urethritis at day 68. Seroconversion to wild-type viral proteins not present in the vaccine was detectable by radioimmunoprecipitation-polyacrylamide gel electrophoresis within 10 days in both patients. Two additional volunteers, one a sex contact of patient 1, seroconverted asymptomatically to nonvaccine proteins during the trial. All four vaccine breakthrough patients were indistinguishable from the other volunteers in the time required to develop neutralizing and ADCC antibodies, in the titer of these antibodies, and the time to seroconversion to gB and gD vaccine proteins. However, only one of the four breakthrough patients had antibodies to g80 (a complex of gC-2 and gE) after vaccination as compared with 15 of the other 18 volunteers (P = 0.05). Neither neutralizing antibody nor ADCC titers consistently identified acquisition of wild-type viral infection; therefore, protein-specific serologies were required to detect wild-type antibodies in these four patients. These data underscore the importance of using serologic assays which will distinguish naturally acquired infection from the immune response to vaccination.

Immune Response to Papillomavirus Infection

Abstract: It is conventional, and convenient, to recognise both antibody-mediated and cell-mediated immune responses to viral infections. Both processes are complex, and there are complex interactions between them, but detailed descriptions of the immune response to some viral infections are available. The antigenic targets are both virions and virus-infected cells that are marked with viral products. The immune response acts to combat initial lodgement of the virus and to prevent reinfection, to modulate the clinical response during an episode of acute infection, and to influence the development of persistent infection. Events that impair immune responsiveness modify the course of infections; sometimes the infecting virus itself contributes to immunosuppression. We understand no infectious disease unless we understand the immune events that determine the clinical outcome. Immune responsiveness is exploited in the diagnosis of viral disease and in the induction of immunity with viral vaccines.

Antibody response of sandhill and whooping cranes to an eastern equine encephalitis virus vaccine

Abstract: As a possible strategy to protect whooping cranes (Grus americana) from fatal eastern equine encephalitis (EEE) viral infection, studies were conducted to determine the immune response of this species and sandhill cranes (Grus canadensis) to a formalin-inactivated EEE viral vaccine. Viral-specific neutralizing antibody was elicited in both species after intramuscular (IM) vaccination. Subcutaneous and intravenous routes of vaccination failed to elicit detectable antibody in sandhill cranes. Among the IM vaccinated cranes, the immune response was characterized by nondetectable or low antibody titers that waned rapidly following primary exposure to the vaccine. However, one or more booster doses consistently elicited detectable antibody and/or increased antibody titers in the whooping cranes. In contrast, cranes with pre-existing EEE viral antibody, apparently induced by natural infection, exhibited a rapid increase and sustained high-antibody titers. Even though EEE virus vaccine induced neutralizing antibody and produced no adverse side effects, further studies will be required to determine the protective efficacy of the antibody.

Efficacy of varicella vaccine in patients with solid tumours.

Abstract: Thirty nine children with malignant disease and without antibodies to varicella zoster virus were immunised with a live Oka strain varicella vaccine. Seroconversion was shown in 24 of those who were vaccinated but five of 18 who responded to the vaccine who were followed up for over six months subsequently lost their antibodies. Of 10 children who were revaccinated, nine responded to the second dose but three lost their antibodies within six months to two years. Four children developed reactions related to the vaccine, one local and three generalised, but all these were transitory and of no clinical concern. Nine of those who were vaccinated, including four who did not respond to the vaccine, have subsequently had close exposure to varicella but none has developed the disease.

Tacaribe virus: a new alternative for Argentine hemorrhagic fever vaccine.

Abstract: Tacaribe virus is know to protect guinea pigs and primates against lethal challenge with Junin virus. A long-term study on the effect of Tacaribe virus infection in the guinea pig was carried out to determine the extent of cross-protection and whether antigen and/or viral persistence and tissue damage could be detected in immune animals. Viral titers, antigen expression in organs, and histologic lesions were sequentially searched for up to 540 days postinfection (pi). Neutralizing antibodies (Abs) and cross-protection to Junin virus were evaluated up to 660 days pi. Tacaribe virus titers and antigen peaked at 7-10 days pi to become undetectable after 30 days pi, except for a transient viral recovery from salivary gland. Virus was undetectable by coculture at 365 and 540 days pi. No immunoglobulins or C3 deposits were detected by immunofluorescence in brain or kidney at any stage, and histologic lesions were absent throughout. Anti-Tacaribe and anti-Junin neutralizing Abs were detected up to 660 days and full protection against challenge was achieved at 365 and 540 days, declining to 33% at 660 days pi. The results warrant consideration of Tacaribe virus as potential heterologous vaccine against Argentine hemorrhagic fever.

Progress towards control of the acute respiratory viral diseases of childhood.

Abstract: Many of the common respiratory illnesses of infancy and childhood are caused by viruses of the Paramyxoviridae family, in particular measles virus, respiratory syncytial (RS) virus and parainfluenzavirus type 3 (PI3). Effective measles vaccine was developed by classical methods, but these same methods have failed to provide vaccines to control RS and PI3 virus infections. The WHO Programme for Vaccine Development was initiated in 1983 to encourage the application of the new biotechnologies to continuing problems, such as the acute virus-induced respiratory diseases of childhood. At a meeting of research workers held in July 1986 under the auspices of this programme, renewed optimism was expressed concerning the prospects for immunoprophylaxis of RS virus-induced disease. Animal models are now available for evaluation of the immunogenic potential of candidate vaccines. Vaccinia/RS recombinant viruses have been produced which have allowed the immunogenic properties of individual RS virus proteins to be defined. Complete protection without the exacerbation of disease, which earlier had accompanied the use of formalin-inactivated vaccines, has been achieved in animals immunized with vaccinia virus recombinants expressing the F protein; partial protection was obtained using G protein gene vectors. PI3 appears to be an inherently stable virus and evidence from animal experiments suggests that bovine PI3 might be suitable for use as a live vaccine in man.

A reassessment of the dual vaccine against rinderpest and contagious bovine pleuropneumonia.

Abstract: In the light of the recent outbreaks of rinderpest in Africa a further assessment of the efficacy of the simultaneous inoculation of rinderpest virus vaccine and contagious bovine pleuropneumonia vaccine was undertaken. Groups of cattle were inoculated with a dual preparation of rinderpest vaccine virus and Mycoplasma mycoides subspecies mycoides or M mycoides alone. These groups were then challenged with M mycoides, first unsuccessfully by an in-contact challenge method and then by subcutaneous challenge. All animals were examined clinically after challenge for evidence of contagious bovine pleuropneumonia and serologically for rinderpest virus and M mycoides mycoides antibodies. There was no evidence that the serological response to the dual vaccine was in any way less than that to either agent given alone and no clinical disease was detected in these animals after in-contact challenge. However, after subcutaneous challenge, the dual vaccinated groups reacted similarly to an unvaccinated control group and unlike the group vaccinated only with M mycoides. This would indicate that the rinderpest virus component of the dual vaccine interfered with the ability of the M mycoides component to induce a fully effective immune response. In the pan African rinderpest campaign the use of the dual vaccine in areas where contagious bovine pleuropneumonia occurs should be carefully considered; in areas where the disease does not occur it is contraindicated.

Biological characteristics of Marek's disease vaccine CVI-988 clone C1.

Abstract: Biological characteristics of Marek's disease virus (MDV) CVI-988 clone C, of importance for vaccine application, are described. CVI-988 clone C was shown to be nonpathogenic for highly MD-susceptible chickens and slightly more effective than prototype CVI-988 vaccine. During plaque purification and serial cell-culture passages, reductions were observed in the release of 'A' antigen from infected cell cultures, in spreading properties and in virus replication in vivo. Pre-licensing batches of CVI-988 clone C vaccine afforded excellent protection against challenge infection with virulent MDV and highly virulent MDV strains. Groups of chickens with bivalent (HVT/SB-1) vaccine-induced maternal antibodies were equally protected by a double dose of CVI-988 clone C vaccine. Field trials performed in the Netherlands and in the United States confirmed the safety and protective efficacy of monovalent CVI-988 clone C vaccine.

Getting to market: the scientific and legal climate for developing an AIDS vaccine.

Abstract: Expectations of a vacana to prevent acquired immunodeficiency syndrome (AIDS) are rising. Not only are the prospects for an effective immunogen improving, but immunization appears to hold the greatest promise for halting the spread of infection and disease.’ Identification of the causal agent-the retrovirus called HTLV-111, LAV, or generically, HIV (human immunodeficiency virus)-has provided the direction and limited the options for containing the disease. Prevention is, of course, critical where the disease must be presumed to be fatal in all cases. Although there is no clear evidence that any single exposure-to.HIV will result in infection or disease, prudence dictates that all exposures be considered potentially infectious and, ultimately, disease-producing until more is known.’ Public education or, more specifically, behavior modification, intended to reduce or eliminate unsafe sexual contact and the sharing of syringes and needles by users of illicit intravenous (IV) drugs, is perhaps the only effective means of prevention that currently exists.’ PubLc education, however, has rarely been sufficiently persuasive to eliminate the transmission of infectious disease, and faces distinct resistance when applied to matters of sexual conduct and illegal drug use.‘ Therefore, while education is necessary, it may not be sufficienr to reduce the risk of exposure to HIV to the level required for damping out the spread of infection.’ Yet vaccine development faces obstacles as significant as those confronting a successful program of public education. The scientific and technical hurdles are themselves formidable. But while the scientific task is becoming clear-

Demonstration of an Immunosuppressive Action of Detergent-disrupted Influenza Virus on the Antibody Response to Inactivated Whole Virus Vaccine

Abstract: SUMMARY In a series of experiments performed in hamsters and mice, administration of mixtures of detergent-disrupted (SV) influenza A X49 (H3N2) virus and inactivated X49 whole virus (WV) vaccine induced lower serum antibody titres than equivalent or lower doses of WV vaccine alone. This reduction in antibody titre was also observed using influenza A (HIN1) and influenza B (B/Hong Kong/8/73) SV and WV vaccine preparations. The results suggested that SV preparations can suppress the serum antibody response to WV vaccine. A suppressive effect of SV influenza virus on WV vaccine was also observed in an in vitro antibody-forming system, using primed mouse spleen cells. In this system, SV induced markedly lower IgG and IgM antibody responses than WV vaccine, and mixtures of SV with WV reproducibly resulted in lowered antibody responses compared to those elicited by WV alone. Possible reasons for these findings are discussed in the light of the known low immunogenicity observed for split and subunit influenza virus vaccine preparations in animals and in unprimed human populations.

Toward new viral vaccines for man.

Abstract: Publisher Summary Targeting of virus research aimed at development of new vaccines is the product of both demands for immunoprophylaxis and feasibilities of producing efficient immunogens Thus, when monolayer cell culture techniques for propagation of a wide range of animal viruses became available at the end of the 1940s, it was logical that the development of a vaccine against poliomyelitis was given highest priority Transposed to the present-day situation, it is obvious that major efforts are focused on the development of a vaccine against acquired immune deficiency syndrome (AIDS) However, this may turn out to be a very complex task because of the unpredictable properties of the surface immunogens of the virus Many different aspects have to be considered in vaccine development In parallel with this development toward future vaccines, the requirements of new products to be introduced on the market will increase In fact, many of the vaccines, which are used today, would have been never introduced for use in humans if they had been evaluated by application even of the current guidelines for vaccine control

Characterization of virulent and attenuated strains of pseudorabies virus for thymidine kinase activity, virulence and restriction patterns

Abstract: A pseudorabies virus mutant lacking thymidine kinase activity (TK-) was isolated and characterized. The mutant replicated as well in cell culture as the parental TK+ strain, was not temperature sensitive at 38.5 degrees C, and did not revert to TK+. Two pseudorabies virus field isolates and three commercial modified live virus vaccine strains were compared for TK activity and virulence for the mouse; all strains expressed TK: Km values for thymidine of the viral TKs ranged from 2.9 to 3.9 microns; the commercial modified live virus vaccine strains were reduced in virulence for the mouse two to ten-fold. The TK- mutant was avirulent for the mouse. Restriction enzyme analysis of the pseudorabies virus DNA from the strains under study revealed that two of the modified live virus vaccine strains are closely related and that all three modified live virus vaccine strains lack the largest PstI fragment characteristic of the other strains included in the study.

Antibody response in cattle to oil emulsion rabies and ephemeral fever vaccines.

Abstract: A stable oil emulsion rabies vaccine with a low viscosity was composed by a formula previously employed for Newcastle disease vaccine. Cattle developed high and sustained antibody levels, and guinea pigs were found to be solidly immune after a single injection of this vaccine. Antibody responses in cattle to 2 oil emulsion ephemeral fever vaccines were not satisfactory after a single injection, and severe local reactions were encountered when booster injections were applied.

Liposome encapsulated subunit (VP1) and virion vaccines against foot-and-mouth disease.

Abstract: Subunit vaccine prepared from VP1 protein of foot-and-mouth disease virus (FMDV) types 0 and Asia 1 protected guinea pigs against FMD and also induced high levels of antibody. Liposomes have been used as a safe and potent immunological adjuvant for FMD vaccines. Vaccines prepared from inactivated virus types 0 and Asia 1 encapsulated in liposomes protected guinea pigs against challenge with homologous virus and showed good antibody response in pigs on a small scale field trial.