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Results for “Protein Subunit Vaccines”

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PubMed1976

Comparison of the humoral and cellular immune response after immunization with live, UV inactivated herpes simplex virus and a subunit vaccine and efficacy of these immunizations.

Antibody and cell-mediated immune responses were measured in rabbits immunized with live, UV inactivated herpes simplex virus or with a subunit vaccine containing envelope proteins. All the types of immunization procedures induced the production of antibody as well as a specific cellular immunity. Furthermore, the subunit vaccine was as effective as the immunization with live or UV inactivated virus to prevent death upon challenge with live HSV. Live HSV induced a transient unresponsiveness of both B and T cells to in vitro stimulation with various mitogens.

Animals↗

PubMed2003

Expression of HC subunits from Clostridium botulinum types C and D and their evaluation as candidate vaccine antigens in mice.

Two proteins representing the heavy-chain subunits of botulinum neurotoxin types C and D were expressed in Escherichia coli, and their vaccine potential was evaluated. Mice were vaccinated with doses ranging from 0.5 to 10 microg and were challenged with 10 to 10(5) 50% lethal doses of toxin. For the type C subunit protein, C50, two doses of 2 microg were required for full protection, while, for type D subunit protein, D50, two 1- microg doses were required. A bivalent vaccine consisting of a mixture of these two proteins also provided protection against both botulinum neurotoxin type C and type D challenge. Antibody levels in serum were determined by both enzyme-linked immunosorbent assays and serum neutralization assays

Animals↗

PubMed2004

Approaches towards the development of a vaccine against tuberculosis: recombinant BCG and DNA vaccine.

The last few years have witnessed intense research on vaccine development against tuberculosis. This has been driven by the upsurge of tuberculosis cases globally, especially those caused by multi-drug-resistant Mycobacterium tuberculosis strains. Various vaccine strategies are currently being developed which can be broadly divided into the so-called living and non-living vaccines. Examples are attenuated members of the M. tuberculosis complex, recombinant mycobacteria, subunit proteins and DNA vaccines. Given current developments, we anticipate that recombinant BCG and DNA vaccines are the most promising. Multiple epitopes of M. tuberculosis may need to be cloned in a vaccine construct for the desired efficacy to be achieved. The technique of assembly polymerase chain reaction could facilitate such a cloning procedure.

BCG Vaccine↗

PubMed1990

Plasmodium berghei subunit vaccine: repeat synthetic peptide of circumsporozoite protein comprising T- and B-cell epitopes fails to confer immunity.

In the murine malaria model induced by Plasmodium berghei, we studied the immunogenicity of the repeat region of the circumsporozoite (CS) protein, which is the main target of the antibody response in infected animals. We immunized several strains with a synthetic peptide--Y(DPPPPNPN)3--corresponding to one of the two P. berghei repeat sequences in complete Freund's adjuvant. Only C57BL/6 immune sera reacted with the synthetic peptide in ELISA and with the native CS protein on P. berghei sporozoites, as detected by immunofluorescence. From lymph node cells of immunized C57BL/6 we isolated two repeat-specific T-cell lines which proliferated in the presence of the synthetic peptide or the recombinant CS protein. We analysed the protective role of this repeat-specific response by injecting infectious sporozoites into mice immunized with irradiated sporozoites or with the repeat peptide. The percentage of mice developing parasitaemia was 80-90% in the peptide-immunized group and only 10-20% in the group immunized with irradiated sporozoites. Anti-repeat antibody titres were comparable in the two groups. On the basis of these results, we can conclude that the T- and B-cell response to the CS repeat obtained with this synthetic peptide immunization is not sufficient for a protective immunity.

Amino Acid Sequence↗

PubMed2003

HPV protein/peptide vaccines: from animal models to clinical trials.

Human Papillomaviruses are viruses that infect the epithelial layers of the oral, rectal, vaginal, and cervical mucosa. There is a causal link between the development of cervical cancer and some other cancers and high-risk human papillomavirus infection (1, 2). Currently there is no prophylactic or therapeutic vaccine available against human papillomavirus infection and its associated lesions. In addition, there exists a high degree of species specificity associated with papillomavirus infection precluding human papillomavirus's use in animal models. Therefore, multiple researchers have utilized a variety of homologous animal papillomaviruses and animal model systems for the development of vaccine strategies against papillomaviruses. The goal of their efforts is to identify vaccine strategies that are efficacious in the animal model systems and translate these strategies into human clinical trials against human papillomavirus. The development of such a vaccine would ultimately result in a reduction in the incidence of cervical cancer and some other HPV-linked cancers and may provide therapy for individuals harboring papillomavirus lesions. This review discusses the advances in papillomavirus vaccinology using proteins/peptides, from the work completed in the animal models to the results of the early human clinical trials.

Animals↗

PubMed2004

Prospects for new TB vaccines: Stop TB Working Group on TB Vaccine Development.

Research towards the development of improved TB vaccines has reached an important turning point. A large number of vaccine candidates such as modified BCG, attenuated Mycobacterium tuberculosis and protein or DNA subunit vaccines, resulting from over a decade of work in experimental laboratory models, are now getting ready for clinical testing. The transition from laboratory to clinical trials has a wide range of strategic and technical implications. Facilities and funding need to be identified for the production of clinical vaccine lots, an issue that is difficult to tackle due to the live organisms in some of the new vaccine candidates; regulatory hurdles need to be overcome; protocols and trial sites need to be developed, for phase III clinical efficacy trials in particular. The Stop TB Working Group on TB Vaccine Development provides a global forum that brings laboratory and clinical researchers together with experts in tuberculosis control and representatives from commercial and non-profit funding agencies to address these issues and to facilitate progress towards the common goal of improved vaccination strategies for tuberculosis.

Animals↗

PubMed1996

Comparative analysis of six European influenza vaccines.

Three split-virion vaccines (Vaxigrip, Begrivac, and Influsplit/Fluarix) and three subunit vaccines containing only viral surface glycoproteins (Influvac, Agrippal, and Fluvirin) available for the 1994-95 season were analysed by biological, molecular, and biochemical methods. Although all vaccines are required by health authorities to contain 15 micrograms haemagglutinin per dose of each virus strain, there were significant differences in haemagglutination titres among the examined vaccines of both types. The enzymatic activity of neuraminidase was present in all vaccines except Fluvirin. Total protein content was lower for subunit vaccines. Viral nucleoprotein was detected in all split vaccines but to varying levels according to SDS-PAGE and Western blot analyses. The ovalbumin content was low in general but was about tenfold higher for Influvac than for the other vaccines analysed. This protein may induce hypersensitive reactions among persons with severe egg allergy. All three split-virion vaccines were found to contain the matrix protein; however, it was not detected in the subunit vaccines. Differences in influenza antigen variety in currently available vaccines may affect efficacy, whereas differences in concentrations of nonviral compounds such as ovalbumin and endotoxin may lead to different postvaccination reactogenicity profiles.

Antigens, Viral↗

PubMed1985

Subunit vaccines against enveloped viruses: virosomes, micelles and other protein complexes.

The envelope proteins (the peplomers) of enveloped viruses are the components that are important for induction of protective immunity. This article reviews methods and problems of making subunit vaccines of peplomers. In the first section, the solubilization of enveloped viruses with detergent is discussed. The preparation of envelope proteins into defined different physical forms is described, i.e. monomeric and micelle forms and the reconstitution of the protein into lipid vesicles (virosomes). Finally, the preparation of a new type of complex is described (named iscom), which is highly immunogenic. In the following sections the efficacy of the different physical forms are reviewed and it is concluded that monomeric forms must be avoided since they are poorly immunogenic and they may even have a suppressive effect on the immune response. The multimeric micelles, virosomes and iscoms are all immunogenic. The iscom is an interesting new concept that can be used to produce efficient subunit vaccines.

Adjuvants, Immunologic↗

PubMed1996

Monoclonal antibodies to surface-exposes proteins of Mycoplasma mycoides subsp. mycoides (small-colony strain), which causes contagious bovine pleuropneumonia.

Outbreaks of bovine pleuropneumonia caused by small-colony strains of Mycoplasma mycoides subsp. mycoides occur in Africa, and vaccination is used for control. Since protein subunits are needed to improve multivalent vaccines, monoclonal antibodies (MAbs) were made to facilitate protein identification and isolation. Eleven immunoglobulin M MAbs derived from mouse spleen donors immunized with disrupted whole organisms bound periodate-sensitive epitopes on externally exposed polysaccharide. Seven of these MAbs caused in vitro growth inhibition of M. mycoides subsp. mycoides; however, reaction with carbohydrate epitopes prevented their use in identifying proteins. Ten additional MAbs from mouse spleen donors immunized with Triton X-114-phase integral membrane proteins reacted with periodate-insensitive, proteinase K-sensitive epitopes. These MAbs were classified into three groups based on immunoblots of Triton X-114-phase proteins. One group reacted with 96-, 16-, and 15-kDa proteins. Another group reacted with 26-, 21-, and 16-kDa proteins, while a third group reacted only with 26- and 21-kDa proteins. One MAb from each group reacted with trypsinsensitive epitopes on live organisms, yet none caused in vitro growth inhibition. Representative MAbs reacted with all small-colony strains in immunoblots and did not react with large colony strains. However, these MAbs were not specific for small-colony strains, as proteins from two other M. mycoides cluster organisms were identified. Nevertheless, MAbs to surface-exposed epitopes on integral membrane proteins will be useful for isolation of these proteins for immunization, since one or more might induce growth-inhibiting antibodies or other protective responses.

Animals↗

PubMed1989

Comparison of Mycoplasma gallisepticum subunit and whole organism vaccines containing different adjuvants by western immunoblotting.

Chickens were vaccinated with subunit (adhesin protein) or whole organisms of Mycoplasma gallisepticum (MG) adjuvanted with multilamellar positively charged liposomes or oil-emulsion. Sera were collected before and following the first (13 weeks of age) and second (17 weeks of age) vaccination. The chicken sera were used in western immunoblotting against whole MG polypeptides. Vaccination with the subunit (MG-adhesin) bacterin containing positively charged liposomes resulted in antibody response specific to adhesin band (75 kD) at 3 weeks post the first and second vaccination; however, crossreactions of the same antibodies occurred to MG proteins of 85 kD (3 weeks after the first vaccination) and 56 kD (3 weeks after the second vaccination). Vaccination with whole MG proteins containing positively charged liposomes resulted in significant immunopotentiation of antibodies against low molecular weight polypeptides of MG (less than 48.0 kD). The addition of Salmonella typhimurium cell wall proteins mitogens (STP) to the different bacterins suppressed the antibody responses to some MG polypeptides.

Adjuvants, Immunologic↗

PubMed1994

Induction of antigen-specific killer T lymphocyte responses using subunit SIVmac251 gag and env vaccines containing QS-21 saponin adjuvant.

Subunit vaccines based on recombinant proteins have proved useful for inducing antibody responses and they are safe for widespread use because they do not contain any live components. Unfortunately, they do not typically induce the types of cell-mediated immune responses required to control viral pathogens; specifically, they do not induce CD8+ cytotoxic T lymphocyte (CTL) responses. To increase the immunogenicity of recombinant proteins, we have used the QS-21 saponin adjuvant in subunit vaccine formulations. In the current study, experimental subunit vaccine formulations containing recombinant p55gag or gp120env proteins from the mac251 strain of the simian immunodeficiency virus (SIVmac251) and the QS-21 adjuvant were used to immunize rhesus macaques. These formulations induced SIV gag- or env-specific cellular immunity that was detectable in vitro and included killer cell activity. The induction of killer cells required prior vaccination and the responses were antigen specific for the immunogens contained in the vaccine formulations. Autologous target cells were required to detect these responses, suggesting genetic restriction, and effector cells appeared to be present in both the CD4+ and CD8+ T lymphocyte subpopulations. These data suggest that the vaccine-induced killer cell activity that was detected was mediated by both CD4+ and CD8+ lymphocytes. Despite the presence of these killer cells, all of the animals became infected with the SIVmac251 on experimental challenge. These findings demonstrated that antigen-specific killer cell responses could be induced by a subunit vaccine formulated with the QS-21 saponin adjuvant. The characteristics of the responses suggested that the effector cells were T lymphocytes, expressing either CD4 or CD8.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed2002

A Tat subunit vaccine confers protective immunity against the immune-modulating activity of the human immunodeficiency virus type-1 Tat protein in mice.

The rational design of new therapies against HIV-1 necessitates an improved understanding of the mechanisms underlying the production of ineffective immune responses to HIV-1 in most infected individuals. This report shows that the CD8(+) T cell responses to gp120 were greatly diminished in mice vaccinated with a bicistronic gp120-Tat DNA vaccine, compared with those induced by a DNA vaccine encoding gp120 alone. The CD8(+) T cell responses induced by the latter included strong gp120-specific IFN-gamma secretion and protective antiviral immunity against challenge by a vaccinia-env pseudotype. The degree to which Tat influenced CD8(+) T cell responses depended on the bioactivity of Tat. Thus, a bicistronic DNA vaccine that expresses gp120 and a truncated Tat defective for LTR activation elicited strong IFN-gamma -secreting CD8(+) T cell responses to gp120 but conferred only marginal protection against the vaccinia-env challenge. The effect of Tat was completely blocked, however, by immunization with inactivated Tat protein before vaccination with the bicistronic gp120-Tat DNA vaccine.

AIDS Vaccines↗

PubMed1995

Galactose oxidation as a potent vaccine adjuvant strategy. Efficacy in murine models and in protection against a bovine parasitic infection.

Potent immunological adjuvants are urgently required to complement subunit protein and peptide vaccines in prophylactic and therapeutic vaccination. Carbonyl-amino condensations, which are essential to the inductive interaction between antigen-presenting cells and T-helper cells, were tested as a target for the enhancement or immune responses to vaccine antigens. Enzymic oxidation of cell surface galactose by the novel adjuvant NAGO, to increase amine-reactive carbonyl groups on lymphocytes and antigen-presenting cells, provided a potent noninflammatory method of enhancing the immunogenicity of viral, bacterial, and protozoal subunit vaccines in mice. In pilot protection studies with a glutathione-S-transferase vaccine against bovine Fasciola hepatica, a formulation containing NAGO as sole adjuvant agent proved very effective in inducing protection. In terms of protection in individual animals, NAGO alone was better than Quil A emulsified in squalene Montanide (five of eight animals were protected better than 80% by NAGO; four of eight animals were protected better than 93% by NAGO; two of eight animals were protected better than 80% by QA/SM). QA/SM (69% mean protection) was, however, more consistent overall than NAGO (65% mean protection). NAGO proved more effective in murine models when combined with muramyl dipeptide, but this combination has yet to be tested in protection studies.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed2001

Respiratory Syncytial Virus: Update on Infection, Treatment, and Prevention.

Respiratory syncytial virus (RSV) infection, which primarily manifests as bronchiolitis or pneumonia, is the leading cause of lower respiratory tract infection in infants and young children. It is associated with more than 100,000 pediatric hospitalizations each year in the United States. Infants who were premature; have chronic lung disease, congenital heart disease, or immunodeficiency disorders; or have underlying metabolic or neuromuscular disorders are at increased risk for especially severe RSV disease. Treatment of children hospitalized with RSV disease is primarily supportive, with administration of supplemental oxygen and fluid replacement therapy. Bronchodilators may benefit at least a subset of such patients. Antiviral therapy with aerosolized ribavirin is available for high-risk, severely ill patients. Handwashing, cleaning of environmental surfaces, and cohorting in hospital settings may decrease RSV transmission. In children born premature and younger than 1 year of age, and in patients with bronchopulmonary dysplasia younger than 2 years of age, passive protection against severe RSV disease may be achieved through monthly injections of anti-RSV antibody (palivizumab) during winter months. No vaccine is available to provide active immunity against RSV, but live attenuated and subunit cloned surface protein vaccines are in development.

Journal Article↗

PubMed2004

Plasmodium falciparum: red blood cell binding studies using peptides derived from rhoptry-associated protein 2 (RAP2).

Plasmodium falciparum rhoptry-associated proteins 1 (RAP1) and 2 (RAP2) are antigens presenting themselves as candidates for a subunit malaria vaccine. RAP2 protein, non-overlapping, consecutive peptides were synthesised and tested in red blood cell (RBC) binding assays to identify their receptor-ligand interaction in recognising RAP2 regions involved in the in vitro merozoite invasion process. Four high activity binding peptides (HABPs) were identified in the resulting 20 peptides. Peptides 26220 ((61)NHFSSADELIKYLEKTNINT(80)), 26225 ((161)IKKNPFLRVLNKASTTTHAT(180)) and 26229 ((241)RSVNNVISKNKTLGLRKRSS(260)) were located in the amino terminal and central part of the protein and HABP 26235 ((361)FLAEDFVELFDVTMDCYSRQ(380)) was located at the carboxy terminal. All these HABPs showed saturable binding and presented dissociation constants between 500 and 950 nM; the number of binding sites per RBC ranged from 48,000 to 160,000. High binding peptides' critical amino acids involved in RBC binding were determined by competition binding assays; their amino acids appear in bold in the sequences shown above. SDS-PAGE results showed that peptides 26220, 26225 and 26229 had at least two different sets of 62 and 42 kDa HABP receptors on RBCs and that peptide 26235 had at least two different sets of 77 and 62 kDa. HABPs inhibited in vitro merozoite invasion by between 54% and 94% at 200 microM, suggesting that these RAP2 peptides are involved in the in vitro P. falciparum invasion process.

Amino Acid Sequence↗

PubMed2006

Immunization of Aotus monkeys with recombinant cysteine-rich interdomain region 1 alpha protects against severe disease during Plasmodium falciparum reinfection.

BACKGROUND: After continuous exposure to malarial infections in regions of Africa where malaria is hyperendemic, children attain clinical immunity. This immunity results, in part, from the acquisition of antibodies against a large repertoire of variant antigens expressed on the surface of infected erythrocytes, such as the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). We determined whether a subunit vaccine to a portion of PfEMP1 could induce protection in nonhuman primates. METHODS: We immunized Aotus nancymai monkeys with PfEMP1 recombinant (r) cysteine-rich interdomain region 1 alpha (CIDR1 alpha ) and infected them twice with P. falciparum Vietnam Oak Knoll strain, the most virulent strain of P. falciparum in Aotus monkeys--each infection expressed a different PfEMP1. Anti-PfEMP1 antibodies were analyzed by enzyme-linked immunosorbent assay against rCIDR1 alpha and by flow cytometry against infected erythrocytes. RESULTS: Immunization with rCIDR1 alpha was not protective, despite delayed patency during the first infection, but it protected monkeys against severe anemia during reinfection. Protection against anemia is associated with a more rapid increase in antibodies to PfEMP1. CONCLUSION: The findings of reduced severe disease in rCIDR1 alpha -vaccinated Aotus monkeys provide experimental support for a PfEMP1-based vaccine to protect African children against severe malarial disease. Such vaccination may function by priming for the accelerated acquisition of immunity to new PfEMP1 variants.

Anemia↗

PubMed1987

Assay, purification and characterization of a recombinant malaria circumsporozoite fusion protein by high-performance liquid chromatography.

The immunodominant repeat region of the malaria circumsporozoite protein from Plasmodium falciparum was purified from a recombinant Escherichia coli to study as a potential subunit vaccine. The recombinant protein, R32Leu-Arg, is composed of 32 tetrapeptide repeat sequences from the circumsporozoite protein (R32) linked to the dipeptide, Leu-Arg. R32Leu-Arg was purified by a series of precipitation steps including temperature, ammonium sulfate, and acid pH treatments; followed by reversed-phase high-performance liquid chromatography (RP-HPLC). An automated RP-HPLC assay was developed to measure the R32Leu-Arg concentration during both fermentation and purification. This assay was used in a variety of applications including measurement of production levels of the antigen during fermentation, evaluation of the protein purification process, quantitation of protein recovery, and as one criterion of protein purity. With minimal changes, the assay conditions were easily adapted to the semi-preparative level to produce 200 mg of purified product. The purified product was characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis; amino acid composition; and analytical size-exclusion and RP-HPLC.

Animals↗

PubMed1995

Evaluation of pig lungs following an experimental challenge with Actinobacillus pleuropneumoniae serotype 1 and 5 in pigs inoculated with either hemolysin protein and/or outer membrane proteins.

Histopathological changes were compared in pigs challenged with Actinobacillus pleuropneumoniae serotype 1 and serotype 5 after inoculation with subunit vaccines. The vaccines consisted of outer membrane protein and/or hemolysin protein isolated from Actinobacillus pleuropneumoniae serotype 1 or both subunits combined. Twenty-seven cross-bred pigs were separated into six groups: Groups I and IV were vaccinated and boostered with 1500 micrograms outer membrane protein; Groups II and V were vaccinated and boostered with 250 micrograms hemolysin protein; Groups III and VI were vaccinated and boostered with a combination of 1500 micrograms outer membrane protein and 250 micrograms hemolysin protein. Groups I, II and III were challenged with A. pleuropneumoniae serotype 1; and Groups IV, V and VI were challenged with A. pleuropneumoniae serotype 5. Groups III and VI demonstrated the least severe lung tissue damage, with significantly lower (P < 0.05) lung involvement as compared to the other groups. Lesions were noted in all six groups. These results showed that complete protection against A. pleuropneumoniae infection was not feasible using a subunit vaccine consisting of just outer membrane protein and hemolysin protein, and that some cross-protection did occur.

Actinobacillus Infections↗