Showing papers on "Viral Vaccine published in 1992"

Antitumor Activity and Immune Responses Induced by a Recombinant Carcinoembryonic Antigen-Vaccinia Virus Vaccine

Abstract: BACKGROUND Human carcinoembryonic antigen (CEA) is a 180-kd glycoprotein expressed in human colorectal, gastric, pancreatic, breast, and non-small-cell lung carcinomas. Previous studies have demonstrated enhanced immune responses to other antigens presented with vaccinia virus proteins via a recombinant vaccinia virus construct. In addition, we have developed a recombinant CEA-vaccinia virus construct, designated rV(WR)-CEA, and have demonstrated humoral anti-CEA responses in mice after immunization with that virus. PURPOSE The goals of this study were (a) to construct a recombinant CEA-vaccinia vaccine in a less virulent vaccinia strain that is potentially safe and effective for treatment of patients whose tumors express CEA and (b) to evaluate the ability of the recombinant CEA-vaccinia vaccine to prevent and reverse tumor growth in mice and to elicit cell-mediated and humoral anti-CEA immune responses. METHODS Using the New York City strain of vaccinia virus, which is used in smallpox vaccination and is more attenuated for humans than rV(WR), we derived a recombinant CEA-vaccinia construct, designated rV(NYC)-CEA. The ability of this construct to induce antitumor immunity was evaluated in mice receiving subcutaneous injections of murine colon adenocarcinoma cells expressing the human CEA gene. RESULTS Administration of rV(NYC)-CEA in mice induced strong anti-CEA antibody responses, as well as CEA-specific cell-mediated responses, including delayed-type hypersensitivity, lymphoproliferative, and cytotoxic responses. Vaccination of mice with the rV(NYC)-CEA rendered them resistant to the growth of subsequently transplanted CEA-expressing tumors. Moreover, when mice were vaccinated 7 days after tumor cell injection, tumor growth was either greatly reduced or eliminated. No toxic effects were observed in any of the mice. CONCLUSION These studies demonstrate that antitumor activity can be induced with the use of a recombinant CEA-vaccinia virus construct derived from an attenuated vaccinia strain, and they reveal the range of cell-mediated and humoral responses induced by this recombinant vaccine.

Efficacy of inactivated whole-virus and subunit vaccines in preventing infection and disease caused by equine infectious anemia virus.

Abstract: We report here on a series of vaccine trials to evaluate the effectiveness of an inactivated equine infectious anemia virus (EIAV) whole-virus vaccine and of a subunit vaccine enriched in EIAV envelope glycoproteins. The inactivated vaccine protected 14 of 15 immunized ponies from infection after challenge with at least 10(5) 50% tissue culture-infective doses of the homologous prototype strain of EIAV. In contrast, it failed to prevent infection in any of 15 immunized ponies that were challenged with the heterologous PV strain. Levels of PV virus replication and the development of disease, however, were significantly reduced in 12 of the 15 ponies so challenged. The subunit vaccine prevented infection from homologous challenge in four of four ponies tested but failed to prevent infection in all four challenged with the PV strain. Two of the four subunit vaccinates had more severe symptoms of equine infectious anemia than nonimmunized ponies infected in parallel. Both vaccines stimulated EIAV-specific cell-mediated immunity. The in vitro lymphoproliferative response was shown to be mediated by T lymphocytes and appeared to be indistinguishable from that induced by EIAV infection. Significant differences were observed in the in vivo lymphocyte responses following challenge with the two virus strains. While peripheral blood mononuclear cells from the inactivated virus vaccinates were equally stimulated by both the prototype and PV strains, the subunit vaccinates challenged with PV exhibited lower levels of spontaneous proliferation and serine esterase activity. This diminished cellular response to PV was correlated with more severe clinical disease in the same ponies. These studies demonstrate for the first time that both an EIAV inactivated whole-virus vaccine and a viral envelope glycoprotein-based subunit vaccine can provide protection against rigorous challenge levels of homologous virus but are unable to protect against similar challenge levels of a heterologous virus. Moreover, the data demonstrate that protection can be achieved in the absence of detectable levels of virus-specific neutralizing antibody in the vaccine recipients at the time of virus challenge. While vaccine-induced virus-specific cell-mediated immune responses were detected, their role in conferring protection was not obvious. Nevertheless, protection from disease appeared to be correlated with the induction of high levels of serine esterase activity following challenge. A significant observation is that while the whole-virus vaccine was usually capable of preventing or markedly moderating disease in the PV-infected ponies, the subunit vaccine appeared to have a high potential to enhance the disease induced by PV infection.(ABSTRACT TRUNCATED AT 400 WORDS)

HIV with Multiple Gene Deletions as a Live Attenuated Vaccine for AIDS

Abstract: Most viral vaccines currently in use in humans are live attenuated strains of virus that lack pathogenic potential. In general, such live attenuated vaccines induce the strongest longest-lasting immunity. Live attenuated strains of human immunodeficiency virus type 1 (HIV-1) have not been previously considered as vaccines for acquired immunodeficiency syndrome (AIDS) because of an inability to envision how their safety could be adequately assured. This report describes a means for making live, nonpathogenic strains of SIVmac and HIV-1 that cannot revert to a virulent form and a stepwise scheme for demonstrating their safety. Replication-competent, multiply deleted derivatives that are currently being tested are missing combinations of auxiliary genes (nef, vpr, vif, vpx, vpu) and certain control elements in the negative regulatory element (NRE) of the long terminal repeat (LTR). Since these genomic regions are in large part conserved among the SIVs and HIVs, they are likely to be important for the virus life cycle in vivo. Consistent with this line of reasoning, a replication-competent nef deletion mutant of SIVmac apparently has lost most or all of its pathogenic potential, yet it still induces strong immune responses. Multiply deleted derivatives of SIVmac and HIV-1 will have to be extensively tested in animal models prior to moving a promising HIV-1 candidate to initial trials in high-risk human volunteers. Definitive evidence for safety and general acceptance for this approach can only evolve gradually over a prolonged period of time.

Vaccination of rhesus monkeys with synthetic peptide in a fusogenic proteoliposome elicits simian immunodeficiency virus-specific CD8+ cytotoxic T lymphocytes.

Abstract: An effective vaccine against the human immunodeficiency virus should be capable of eliciting both an antibody and a cytotoxic T lymphocyte (CTL) response. However, when viral proteins and peptides are formulated with traditional immunological adjuvants and inoculated via a route acceptable for use in humans, they have not been successful at eliciting virus-specific, major histocompatibility complex (MHC) class I-restricted CTL. We have designed a novel viral subunit vaccine by encapsulating a previously defined synthetic peptide CTL epitope of the simian immunodeficiency virus (SIV) gag protein within a proteoliposome capable of attaching to and fusing with plasma membranes. Upon fusing, the encapsulated contents of this proteoliposome can enter the MHC class I processing pathway through the cytoplasm. In this report, we show that after a single intramuscular vaccination, rhesus monkeys develop a CD8+ cell-mediated, MHC class I-restricted CTL response that recognizes the synthetic peptide immunogen. The induced CTL also demonstrate antiviral immunity by recognizing SIV gag protein endogenously processed by target cells infected with SIV/vaccinia recombinant virus. These results demonstrate that virus-specific, MHC class I-restricted, CD8+ CTL can be elicited by a safe, nonreplicating viral subunit vaccine in a primate model for acquired immune deficiency syndrome. Moreover, the proteoliposome vaccine formation described can include multiple synthetic peptide epitopes, and, thus, offers a simple means of generating antiviral cell-mediated immunity in a genetically heterogeneous population.

Epidemiology and control of Japanese encephalitis.

Abstract: Japanese encephalitis (JE) remains endemo-epidemic in several countries in East, South-East and South Asia The disease has been under control in Japan since the 1970s owing to mass immunization using mouse-brain-derived inactivated vaccine and to reduced vector mosquito populations The vector density which was once reduced by wide spraying of insecticides in rice fields showed an increasing trend after the 1980s as a result of mosquito resistance In the Republic of Korea, the number of JE cases showed a significant decrease after 1983 also because of mass immunization using mouse-brain-derived vaccine On the other hand, large outbreaks of JE continued to occur in China, Viet Nam, Thailand, India, Nepal and Sri Lanka In China, a hamster-kidney cell-derived vaccine was developed and used for human immunization Besides human JE, the fatal outcome of equine JE is an economic problem in China Current JE vaccine derived from mouse brain is highly purified and its safety and efficacy have been proved by field-tests as well as laboratory experiments In spite of slight antigenic differences among JE virus isolates, JE vaccine produced by a classical Nakayama strain was effective in preventing overt JE in a field study in Thailand The technology of mouse-brain-derived inactivated JE vaccine production was transferred from Japan to India, Thailand and Viet Nam The production of JE vaccine in these countries is still on a pilot scale and insufficient for mass-immunization of susceptible target populations(ABSTRACT TRUNCATED AT 250 WORDS)

Vaccine storage practices in pediatric offices.

Abstract: Fifty pediatric offices and clinics in the metropolitan Los Angeles area were visited to assess vaccine storage practices. Questionnaires were administered to the personnel responsible for vaccine storage and the vaccine refrigerators were inspected. Only 16% of vaccine storage coordinators could cite appropriate storage temperatures for vaccines and 18% were unaware that heat can harm certain vaccines. Refrigerator thermometers were checked at least weekly in only 20% of offices, and 22% of the refrigerators had inappropriately high temperatures. Vaccines were routinely stored outside of the refrigerator uninsulated during the practice day in 16% of the offices visited. It is concluded that vaccine storage errors occur in pediatric offices at an unacceptably high frequency. Pediatricians should familiarize themselves with the guidelines for optimal vaccine storage in order to minimize the potential for vaccine failure in primary care practice.

Inactivated whole-virus vaccine derived from a proviral DNA clone of simian immunodeficiency virus induces high levels of neutralizing antibodies and confers protection against heterologous challenge.

Abstract: We tested the ability of macaques vaccinated with inactivated whole simian immunodeficiency virus (SIV) to resist challenge with either homologous or heterologous cell-free uncloned SIV administered by the intravenous route The vaccine virus was derived from a proviral DNA clone and thus was considered genetically homogeneous Sixteen macaques received either hepatitis B surface antigen (n = 6) or the inactivated whole-SIV vaccine (n = 10) at weeks 0, 4, and 49 of the study All SIV vaccine recipients developed high levels of homologous and heterologous neutralizing antibodies in response to vaccination At the time of challenge (week 53), vaccinees were further stratified to receive either homologous (n = 10) or heterologous (n = 6) uncloned live SIV The envelope glycoproteins of the homologous and heterologous challenge viruses were 94% and 81% identical to the vaccine virus, respectively Regardless of challenge inoculum, all vaccinees in the control group (hepatitis B surface antigen) became infected, whereas all SIV vaccinees were protected against detectable infection These data support the concept that an efficacious vaccine for HIV might be possible, and suggest that genetic variation of HIV might not be an insurmountable obstacle for vaccine development

Protective immunization against Epstein-Barr virus-induced disease in cottontop tamarins using the virus envelope glycoprotein gp340 produced from a bovine papillomavirus expression vector.

Abstract: Inoculation with Epstein-Barr virus (EBV) induces malignant lymphomas in the cottontop tamarin (Saguinus oedipus oedipus). This provides an experimental animal model for assessing the efficacy of candidate EBV vaccines which are intended to reduce the incidence of human tumours associated with EBV infection. Previous work has shown that experimental vaccines based on the major virus envelope glycoprotein gp340 prepared from the membranes of EBV-infected cells are effective in protecting cottontop tamarins against EBV-induced disease. However, not all purified gp340 preparations induce protective immunity against EBV lymphoma in the tamarin. In this work, cottontop tamarins were immunized with recombinant gp340, produced using a bovine papillomavirus (BPV) expression vector, and a threonyl muramyl dipeptide adjuvant formulation. Although the recombinant-derived gp340 lacked the membrane anchor sequence of authentic gp340 and was expressed in mouse cells, it was immunogenic and induced virus-neutralizing antibodies. Healthy vaccinated tamarins were protected against EBV-induced disease. The demonstration that a recombinant gp340 product is able to elicit protective immunity in the cottontop tamarin is a significant step in the development of an EBV vaccine because previously it had not been clear whether a recombinant product would have the exact tertiary structure, including the necessary carbohydrate components, to induce protective immunity. A recombinant gp340 vaccine offers various advantages over production of the authentic molecule by laborious biochemical separation, including lower cost and the absence of potentially oncogenic EBV DNA. Therefore, recombinant gp340 produced using the BPV expression vector is suitable for development as a candidate EBV vaccine for a human Phase I trial and beyond.

Evaluation of a live attenuated, cold-adapted parainfluenza virus type 3 vaccine in children.

Abstract: Cold passage 18 (CP18) parainfluenza virus type 3 (PIV-3) vaccine was evaluated in a double-blind, randomized, placebo-controlled study of 95 infants and young children. None of 19 seropositive older children 41 to 124 months old became infected when 10(6) 50% tissue culture infective doses (TCID50) of vaccine virus was administered intranasally. Two of nine and seven of twenty-four young seropositive children given 10(5) or 10(6) TCID50 of CP18 PIV-3, respectively, became infected. Each of four seronegative young children became infected, as indicated by virus shedding and antibody response, when given 10(6) TCID50 of CP18 PIV-3 intranasally. Illness was not observed in seropositive children. Two of the four seronegative children developed a mild illness characterized by rhinorrhea and wheezing on auscultation; none had fever. In one case, vaccine virus spread from a vaccine to a sibling control but did not cause illness. The vaccine is attenuated relative to wild-type PIV-3, but additional attenuation will be required to achieve a satisfactory PIV-3 vaccine.

Safety and immunogenicity of oral tetravalent human-rhesus reassortant rotavirus vaccine in neonates.

Abstract: We conducted a prospective randomized double blind study to determine: (1) the safety and immunogenicity of live oral tetravalent human-rhesus rotavirus reassortant vaccine in neonates; and (2) whether a second dose at the age of 6 to 8 weeks enhances the immunogenicity. Two hundred forty healthy neonates were enrolled and received vaccine (183) or placebo (57) on the second day of life. At the age of 6 to 8 weeks 133 received placebo and 88 received a second dose of vaccine. Medical events were noted within 10 days from vaccine administration in 6 of 183 (3.3%) vaccine recipients vs. 0 of 57 placebo recipients (P = 0.34) after the first dose and in 8 of 88 (9%) vs. 4 of 133 (3%) after the second dose (P = 0.069); none was severe and all were of short duration. Seroresponse of any type (detectable IgA or 4-fold increase of titer to rhesus rotavirus was 9% for the placebo, vs. 52 and 46% for those who received one and two doses of vaccine, respectively. However, neutralizing antibodies against human serotypes 1, 2 and 3 were not raised successfully in vaccinated infants when compared with placebo recipients. The same pattern was found when geometric mean titers were compared. Vaccine take was better when cord blood titers were low. At the age of 1 year the vaccinees had more often high titers for antirhesus rotavirus antibodies (> 640) than the placebo recipients (49% vs. 0%; P < 0.001). NO difference was found between the groups in neutralizing antibodies to human serotypes 1, 2 and 3 rotavirus.(ABSTRACT TRUNCATED AT 250 WORDS)

Herpes simplex vaccines

Abstract: Publisher Summary This chapter reviews the unique problems of Herpes Simplex Virus (HSV) infections and discusses some of the approaches in the development of a vaccine directed against the HSV disease that have been tried in the past. HSV infections have been recognized since the time of the ancient Greeks. As with many other transmissible infections of humans, prevention of disease by vaccines has been attempted for nearly two centuries without apparent success. Observations from these early vaccine efforts included the appearance of lesions at the vaccine site and the development of recurrent lesions following either natural disease or immunization. As with other viral vaccines, the development of an HSV vaccine has attracted the interest of investigators for the better part of the 20th century.

A tissue culture vaccine with lapinized chinese (LC) strain of hog cholera virus (HCV).

Abstract: The lapinized chinese (LC) strain of hog cholera virus (HCV), was adapted to grow in a cell line from minipig kidney (MPK) where it reached a titer, as determined by immunofluorescence, significantly higher than in rabbits. Inasmuch as the immune serum to HCV neutralized the culture-adapted virus, it was concluded that its antigenicity did not undergo any change after adaptation to MPK cells. The MPK-LC adapted virus (MPK-LC-HCV) showed also a higher immunogenic activity in rabbits, in comparison with the original LC virus. The MPK-LC-HCV protected pigs against challenge infection with virulent HCV. Thus, the vaccinated pigs did not show any clinical signs of disease, nor have they been responsible of virus shedding after they were exposed to the challenge infection 1 month or 6 and 11 months later. All vaccinated pigs seroconverted after vaccination and the antibody titers were on the same range of those reported in pigs vaccinated with the traditional vaccine prepared in rabbits. In the same pigs the antibody concentration underwent a booster effect following challenge infection. It was suggested the MPK-LC-HCV vaccine as an alternative product that might be used to prevent HCV infection. prevent HCV infection.

Varicella vaccine: still at the crossroads.

Abstract: Dr Saul Krugman was and continues to be a teacher, mentor, and inspiration to many in the field of infectious diseases, particularly with regard to viral infections and immunizations. It is therefore a great privilege to play a role in celebrating his 80th birthday, and it also seems appropriate to honor him with a presentation concerning live attenuated varicella vaccine. Dr Krugman was greatly responsible for bringing about clinical trials with varicella vaccine in the United States, and in fact, without his input it is unlikely that this vaccine would ever have been tested here. His recognition, in the 1950s, of the potential severity of varicella in adults was a landmark paper in the realization that varicella is not always a benign disease and is worth preventing.1 The conventional wisdom, however, has been that there was no need for a varicella vaccine because the disease is too mild to warrant immunization. There are, nevertheless, numerous well-recognized complications of varicella. The most common is bacterial superinfection which may be local and mild but on occasion may be systemic and even fatal (such as staphylococcal pneumonia). In 1984, Preblud and his colleagues2 estimated that each year in the United States, as the result of chickenpox, 56 otherwise healthy children die, 46 develop encephalitis, more than a quarter of a million children visit a physician, and physicians write a similar number of prescriptions for antipruritics and antibiotics. Moreover, children at high risk to develop severe or chronic forms of chickenpox, such as leukemics, those who have had organ transplants, and those with human immunodeficiency virus infection, are often denied such activities as attending school and social functions for fear of an unrecognized exposure to varicella.

New approaches to flavivirus vaccine development.

Abstract: Publisher Summary This chapter discusses new approaches to flavivirus vaccine development. Flaviviruses are small, enveloped single-positive strand RNA viruses of the newly established family, Flaviviridae. Genetically and serologically related to each other, the 68 known flaviviruses include a large number of arthropod-borne agents of human disease, the most important of which, in terms of prevalence and pathogenicity, are the mosquito-borne yellow fever, dengue, and Japanese encephalitis viruses, and the far eastern and western subtypes of tick-borne encephalitis virus. The chapter presents recent advances in the molecular biology of flaviviruses that will offer novel alternatives to further flavivirus vaccine development. The capacity of medically important flaviviruses to cause lethal encephalitis in mice has been invaluable in the early assessment of candidate vaccine preparations. However, inadequacy of this model as a reliable measure of vaccine attenuation or protective immunogenicity in humans, where the pathogenesis of flaviviral disease may be vastly different, cannot be too strongly emphasized. In the case of dengue where infection of monkeys is clinically unapparent, the absence of a suitable experimental model of human infection presents a formidable barrier to the understanding of the pathogenesis of this disease and to the development of a vaccine against it.

Analysis of glycoprotein I (gI) negative and aberrant pseudorabies viral diagnostic isolates.

Abstract: Glycoprotein I (gI) phenotypes and genotypes of 4 pseudorabies viral diagnostic isolates were evaluated by use of in vitro DNA amplification, monoclonal antibody binding, gI-specific serodiagnostic responses, and in vivo virulence approaches. Three viruses were avirulent and did not elicit gI-specific serologic responses, react with gI-specific monoclonal antibodies, or contain gI epitope-encoding DNA sequences. The fourth virus was virulent and did elicit a gI-specific serodiagnostic response. Compared with reference virulent pseudorabies viruses, however, the fourth isolate had reduced reactivity with a group of gI monoclonal antibodies and had a single nucleotide sequence substitution with a corresponding putative amino acid change in the epitopically dominant portion of the gI molecule. Presumably, the first 3 isolates represented diagnostic recoveries of viruses derived from gI-deleted modified-live pseudorabies viral vaccines, whereas the fourth isolate was a virulent but gI-aberrant wild-type virus. Thoroughly assessing the gI status of pseudorabies viral diagnostic isolates was considered to be essential in evaluating the epidemiologic importance of these viruses and in monitoring the validity of gI-based vaccine companion tests now used worldwide in pseudorabies control and eradication programs.