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Results for “Vaccines, Subunit”

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PubMed2000

Vaccination of seropositive subjects with CHIRON CMV gB subunit vaccine combined with MF59 adjuvant for production of CMV immune globulin.

The safety and immunogenicity of four different regimens of CHIRON cytomegalovirus (CMV) gB subunit vaccine combined with MF59 adjuvant and administered to seropositive plasma donors were evaluated to ascertain whether vaccination of seropositive subjects would significantly increase antibody titer to gB glycoprotein. This was done to select the best vaccination regimen for generating high-titered plasma for manufacture of CMV immune globulin. No serious adverse events were attributed to this vaccine, and the vaccine was well tolerated. Only the first dose of vaccine in each regimen stimulated a four-fold or greater antibody response to gB glycoprotein and each regimen induced similar antibody titers. However, initial vaccination followed by a 1 week rest from plasmapheresis and two booster vaccinations at 8 and 24 weeks, each followed with another 1 week rest from plasmapheresis, maintained the highest geometric mean gB ELISA titer of the four regimens over the 34-week post-vaccination period. CMVIG manufactured from a pool of high titered plasma units from two of four subject groups had gB ELISA and neutralizing antibody titers nine and six times higher, respectively, compared to Cytogam, indicating that vaccination of seropositive subjects with CHIRON gB vaccine combined with MF59 adjuvant prior to harvesting plasma can enhance functional antibody in a CMVIG product.

Adjuvants, Immunologic↗

PubMed1989

Immune response gene regulation of immunity to Plasmodium berghei sporozoites and circumsporozoite protein vaccines. Overcoming genetic restriction with whole organism and subunit vaccines.

We conducted a series of experiments to define Ir gene regulation of the immune response to Plasmodium berghei sporozoites and circumsporozoite (CS) protein-derived subunit vaccines. The studies demonstrated that there is no apparent genetic restriction of the capacity to develop protective immunity against a large sporozoite challenge after immunization with irradiation-attenuated P. berghei sporozoites; that the Th response to (Asp-Pro-Ala-Pro-Pro-Asn-Ala-Asn)n, the predominant protective B epitope on the P. berghei CS protein, is genetically restricted and regulated by Class II genes (I-Ab) and by genes in the Class I region (H-2Dk) or telomeric to this region; and that this restriction can be overcome by immunization with a r protein including the entire P. berghei CS protein. The results support the development of full length human CS protein vaccines to take advantage of all potential T epitopes on this protein.

Amino Acid Sequence↗

PubMed1992

Initiation of cytotoxic T-cell response and protection of Balb/c mice by vaccination with an experimental ISCOMs respiratory syncytial virus subunit vaccine.

Respiratory syncytial virus is an important human pathogen causing serious lower respiratory tract infections of children and elderly people. Previous studies on the development of experimental subunit vaccines either expressed by recombinant DNA technology or prepared from purified viral proteins absorbed on adjuvant (ISCOMs) have shown promise. The present work reports on the effectiveness of an experimental ISCOMs vaccine in initiating humoral and cell-mediated immune responses and in providing overall protection upon live virus challenge in Balb/c mice; results indicate that vaccination by the intramuscular route is more effective, even if vaccination by the intranasal route also significantly reduced virus shedding.

Animals↗

PubMed2003

Immunogenicity and safety of a novel liposomal influenza subunit vaccine (INFLUSOME-VAC) in young adults.

Influenza and its complications account for substantial morbidity and mortality among young adults and especially among the elderly. In young adults, immunization provides 70-90% protection, while among the elderly the vaccine may be only 30-40% effective; hence the need for new, more immunogenic vaccines. We compared the safety and immunogenicity of a novel IL-2-supplemented liposomal influenza vaccine (designated INFLUSOME-VAC) with that of a commercial subunit vaccine and a commercial split virion vaccine in young adults (mean age 28 years) in the winter of 1999-2000. Seventy-three healthy young adults were randomly assigned to be vaccinated intramuscularly with the following: a commercial subunit vaccine (n = 17, group A), INFLUSOME-VAC (n = 36, group B), and a commercial split virion vaccine (n = 20, group C). The three vaccines contained equal amounts of hemagglutinin (approximately 15 microg each) from the strains A/Sydney (H3N2), A/Beijing (H1N1), and B/Yamanashi. INFLUSOME-VAC induced higher geometric mean HI titers and higher-fold increases in HI titers against all three strains, compared with the two commercial vaccines. In addition, seroconversion rates for the A/Sydney and B/Yamanashi strains were significantly higher (P < 0.05) compared with the split virion vaccine, and significantly higher for the three strains compared with the subunit vaccine (69-97% vs 35-65%, P < or = 0.02). Moreover, the anti-neuraminidase response was significantly greater (P = 0.05) in group B vs group A. INFLUSOME-VAC caused mild local pain at the injection site in a significantly higher proportion of the vaccinees (83%). Thus, INFLUSOME-VAC is an immunogenic and safe vaccine in young adults.

Adolescent↗

PubMed2003

[Comparative study on safety and immunogenicity between influenza subunit vaccine and split vaccine].

OBJECTIVE: To compare the reactogenicity and serology between influenza subunit vaccine and split vaccine. METHODS: A randomized, double-blind study was carried out among children (age 6 - 12 years) in order to compare the safety and immunogenicity of an influenza inactivated subunit vaccine (Agrippal, Chiron Vaccines) with that of a split vaccine (Flurix, GSK). RESULTS: A total of 499 subjects were vaccinated and included in the safety analysis. A total of 249 subjects received Agrippal and 250 received Flurix. All subjects were kept under medical observation for 30 minutes in order to check the evidence of having any immediate local and systemic reaction. Daily observation records were collected during the 3-day follow-up after vaccination. 6.4% of the cases with fever >or= 37.5 degrees C was reported in the Flurix group, but 2.4% in Agrippal group which was significantly less than the former group (P > 0.05). Blood samples (the D0 pre- and D23 post-vaccination sera) were collected from 224 of Agrippal group and 223 of Flurix group and analysed by the haemagglutination inhibition (HI) assay. Agrippal and Flurix induced similar seroprotection (HI titer >or= 1:40, H1N1 99.6% vs 100.0%; H3N2 99.1% vs 99.1%) and seroconversion (4-fold increase, 95.1% vs 97.8%; H3N2 74.5% vs 79.8%) rates and geometric mean titer (GMT) increase (16.0 vs 21.0; 5.4 vs 6.4) against the two A subtypes. A similar seroprotection rate (94.2% vs 96.4%) and GMT increase (21.2 vs 18.2) against the influenza B strain were also noticed in both vaccines. No significant difference was found in the results of immunological assay between the two vaccines (P < 0.05). A lower seroconversion rate against B strain was observed in Agrippal group than in Flurix group (91.1% vs 97.3%). CONCLUSION: In terms of safety, both vaccines were generally well tolerated. The fever reaction was less frequently seen in the Agrippal group. Both vaccines induced an effective immune response in the vaccines.

Antibodies, Viral↗

PubMed2000

Effects of interleukin-12 in the long-term protection conferred by a Mycobacterium avium subunit vaccine.

The effects of the addition of recombinant interleukin (IL)-12 to a mycobacterial subunit vaccine were analyzed in terms of the longevity of the protective immunity generated. BALB/c mice were immunized with culture filtrate proteins from Mycobacterium avium with dimethyl-dioctadecilammonium bromide (DDA) as an adjuvant. This subunit vaccine induced protection against a challenge by M. avium which lasted for at least 6 months while waning with time until 1 year postvaccination. Whereas the addition of IL-12 enhanced the initial protective efficacy of this subunit vaccine during the first 6 months, it accelerated the loss of protective efficacy observed at 1 year postvaccination. These data confirm the adjuvant properties of IL-12 in vaccines against mycobacteria and raise the possibility of late counter-protective untoward effects.

Adjuvants, Immunologic↗

PubMed2005

Protection of macaques against Mycobacterium tuberculosis infection by a subunit vaccine based on a fusion protein of antigen 85B and ESAT-6.

Various new tuberculosis (TB) vaccine candidates in combination with new delivery systems, including subunit vaccines, are currently being evaluated by a number of laboratories. One vaccine candidate that has shown promising protective capacity in mice and guinea pigs is a fusion of Ag85B and ESAT-6. In this study, we have investigated the efficacy of this Ag85B-ESAT-6 fusion protein vaccine in a non-human primate model for TB. Vaccination of cynomolgus monkeys with the Ag85B-ESAT-6 fusion protein in two different adjuvant (DDA/MPL, AS02A) resulted in a reduction in bacterial number and/or lung pathology in animals challenged with Mycobacterium tuberculosis. Vaccination prevented an increase in C-reactive protein serum levels, general activation of CD4 and CD8 subsets and boosted development of humoral and cellular immune responses to a spectrum of mycobacterial antigens on exposure to M. tuberculosis infection. We show, in two independent experiments, that vaccination of primates with Ag85B-ESAT-6 induces protective immune responses, suggesting that Ag85B-ESAT-6 is a strong candidate for further clinical evaluation. As far as we are aware this is the first report of protection in primates with a subunit vaccine.

Acyltransferases↗

PubMed1989

The effect of human recombinant interleukin-2 on the porcine immune response to a pseudorabies virus subunit vaccine.

The effect of human recombinant interleukin-2 (rIL-2) as an immune enhancing agent was evaluated in pigs vaccinated with a pseudorabies virus subunit vaccine (SV). Two groups of three pigs received two 25 micrograms doses of SV given 3 weeks apart. One group received 10(5) kg-1 day-1 of rIL-2 subcutaneously over two 5-day periods beginning on the day of the first and second vaccine inoculation. Six other pigs were immunized with two 5 micrograms doses of SV. Three of these pigs were treated as above with rIL-2. The effect of treatment was evaluated by comparing: the humoral response; the cell-mediated immune (CMI) response as measured by lymphocyte blastogenesis before and after virus challenge; and the weight response and virus excretion pattern after challenge with virulent pseudorabies virus (PRV). The humoral antibody response as detected by the serum virus neutralization (SN) assay and the enzyme linked immunosorbent assay (ELISA) was consistently higher in rIL-2 treated pigs than in non-treated pigs. These differences were significant (P less than 0.05) among high vaccine dose pigs prior to virus challenge when measured by the SN assay and during the anamnestic response period between days 3 and 10 after challenge when measured by both the SN assay and the ELISA. No differences were detected between treatment groups in the weight response, virus excretion pattern or the CMI response. These results suggest that human rIL-2 may have enhanced the immune response of pigs to the subunit vaccine.

Animals↗

PubMed2003

A subunit vaccine against the adenovirus egg-drop syndrome using part of its fiber protein.

In this study, the effectiveness of antibodies against the hexon, fiber or a fiber fragment of an avian adenovirus egg-drop syndrome (EDS), in neutralizing the virus was tested. The fiber protein is responsible for binding the virus to the target cell. The fiber fragment knob-s comprises the carboxy-terminal knob domain and 34 amino acids of the immediately adjacent shaft domain of the adenovirus fiber protein. The hexon, fiber capsid protein and knob-s were produced in E. coli and injected into chickens. Antibodies that were produced against the whole fiber protein showed some hemagglutination inhibition (HI) activity. Antibodies produced against the knob-s protein showed HI activity and serum neutralization (SN) activity similar to the positive control-whole virus vaccine. We assume that production of only part of the fiber enables the protein produced in E. coli to fold correctly. Antibodies produced against the hexon protein showed no SN activity. In summary, knob-s induced SN and HI antibodies against EDS virus at a rate similar to the whole virus and were significantly more efficient than the full-length fiber. The recombinant knob-s protein may be used as a vaccine against pathogenic adenovirus infections.

Adenoviridae Infections↗

PubMedDate not supplied

[Vaccination of weaner pigs against classical swine fever with the subunit vaccine "Porcilis Pesti": influence of different immunization plans on excretion and transmission of challenge virus].

Excretion and transmission of CSFV after vaccination with the CSF subunit marker vaccine "Porcilis Pesti" have been studied using the following different vaccination schedules: Group A--two vaccinations with an interval of 28 d, challenge 14 d after second vaccination (p.v2.); group B--two vaccinations with an interval of 14 d, challenge 14 d later; group C--two vaccinations with an interval of 28 d, challenge at time of booster vaccination; group D--two vaccinations with an interval of 14 d, challenge 7 d p.v2.; group E--single vaccination and infection 14 d later. After infection one sentinel pig was added to the vaccinated and infected pigs of each group. A single vaccination did not induce protective immunity against a CSFV challenge. Double vaccination at a four-week interval protected piglets from clinical infection, and neither viraemia and leukopenia nor virus excretion were detected if infected 14 d p.v2. Two vaccinations at a two-week interval followed by a challenge 7 d p.v2. led to a short viraemia on day 5 p.i. but without excretion of CSFV. Though all other vaccination schedules induced a reduction in virus shedding and a decrease in CSFV replication, in all these cases in-contact controls became infected. The results of transmission of CSFV are discussed in relation to a potential use of subunit marker vaccines in CSF control.

Animals↗

PubMed1996

Prospects for subunit vaccines against tick-borne diseases.

Tick-borne parasites are a serious impediment to the improvement of live-stock production in the developing world. The major parasites affecting cattle include Theileria parva, T. annulata, Babesia bigemina, B. bovis, Anaplasma marginale and Cowdria ruminantium. The control of these infections is dependent on the use of acaricides to decrease transmission by the tick vectors, and immunization of susceptible animals with live vaccines. The use of acaricide is hampered by the development of resistance, and live vaccines require cold chain facilities, which are generally unreliable in developing countries. There is therefore a need for improved vaccines that can circumvent these problems. There is a subunit vaccine being developed for T. parva based on the major surface antigen of the sporozoite (p67). A similar antigen, SPAG 1, has been identified as a candidate for T. annulata. Although several candidate antigens have been identified for Babesia spp., progress towards development of a subunit vaccine based on these antigens has been hampered by polymorphism among isolates and between species, and lack of knowledge of the immune effector mechanisms responsible for protection. The search for protective antigens of A. marginale has focused on outer membrane proteins; immunization with a variety of these antigens alone or in combination, has yielded promising results. As with Babesia, further definition of immune effector mechanisms is needed to optimize immunization strategies. The work on identifying the protective antigens of C. ruminantium is in its embryonic stages; however, two antigens have been identified and are currently being evaluated. There is high expectancy for subunit vaccines for all these diseases; however there is need for further work to elucidate the immune mechanisms in order to select appropriate antigen delivery systems.

Anaplasma↗

PubMed1990

Effect of immunomodulator adamantylamide dipeptide on antibody response to influenza subunit vaccines and protection against aerosol influenza infection.

Adamantylamide dipeptide (AdDP) is a novel synthetic compound combining the antiviral properties of amantadine and the essential adjuvant activity of immunomodulator muramyl dipeptide. Mice were immunized with influenza A/Taiwan/1/86 (H1N1), A/Sichuan/2/87 (H3N2) and influenza B/Beijing/1/87 subunit vaccines containing AdDP or aluminium hydroxide (Al(OH)3). Induction of homologous haemagglutination-inhibition (HI) antibodies and correlation to protection against lethal aerosol influenza A/PR/8/34 (H1N1) infection were investigated. Subunit vaccine containing A/Sichuan (H3N2) and Al(OH)3 stimulated high HI antibody titres but failed to provide protection against heterologous influenza A (H1N1) challenge infection following either the primary or the secondary immunizations. In contrast, similar treatment with A/Sichuan subunit vaccine containing AdDP conferred significant protection against heterologous challenge despite low levels of circulating antibody. Primary immunization with even influenza B/Beijing subunit vaccine containing AdDP, but not Al(OH)3, provided partial protection against influenza A challenge. These results suggest that appropriate immunomodulators like AdDP can convert restricted homotypic immunity induced by inactivated influenza subunit vaccines to advantageous cross-reacting type of heterologous response.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1988

Herpes simplex virus (HSV)-specific proliferative and cytotoxic T-cell responses in humans immunized with an HSV type 2 glycoprotein subunit vaccine.

Studies were undertaken to determine whether immunization of humans with a herpes simplex virus type 2 (HSV-2) glycoprotein-subunit vaccine would result in the priming of both HSV-specific proliferating cells and cytotoxic T cells. Peripheral blood lymphocytes (PBL) from all eight vaccines studied responded by proliferating after stimulation with HSV-2, HSV-1, and glycoprotein gB-1. The PBL of five of these eight vaccines proliferated following stimulation with gD-2, whereas stimulation with gD-1 resulted in relatively low or no proliferative responses. T-cell clones were generated from HSV-2-stimulated PBL of three vaccinees who demonstrated strong proliferative responses to HSV-1 and HSV-2. Of 12 clones studied in lymphoproliferative assays, 9 were found to be cross-reactive for HSV-1 and HSV-2. Of the approximately 90 T-cell clones isolated, 14 demonstrated HSV-specific cytotoxic activity. Radioimmunoprecipitation-polyacrylamide gel electrophoresis analyses confirmed that the vaccinees had antibodies only to HSV glycoproteins, not to proteins which are absent in the subunit vaccine, indicating that these vaccinees had not become infected with HSV. Immunization of humans with an HSV-2 glycoprotein-subunit vaccine thus results in the priming of T cells that proliferate in response to stimulation with HSV and its glycoproteins and T cells that have cytotoxic activity against HSV-infected cells. Such HSV-specific memory T cells were detected as late as 2 years following the last boost with the subunit vaccine.

Cell Line↗

PubMedDate not supplied

[Evaluation of the effectiveness of influenza trivalent polymer subunit vaccine "Grippol"].

Influenza polymer-subunit vaccine "Grippol", made up of the sterile conjugate of surface proteins of influenza viruses, groups A and B, with polyoxidonium (copolymer), was obtained at the State Scientific Centre of Research Institute of Immunology. As the result of our investigations, the coefficient of prophylactic effectiveness of vaccine "Grippol" was found to be 71%; in the presence of the 50% immune stratum in the group the coefficient of antiepidemic protection was found to be 66.4%. At the same time, cases of influenza and acute respiratory diseases were shown to take a milder form in persons immunized with vaccine "Grippol" than in the group of nonimmunized subjects. The results of this investigation did not show any side effects caused by the vaccine.

Adolescent↗

PubMed2007

Therapeutic synergy of human papillomavirus E7 subunit vaccines plus cisplatin in an animal tumor model: causal involvement of increased sensitivity of cisplatin-treated tumors to CTL-mediated killing in therapeutic synergy.

PURPOSE: The goal of this study was to investigate the therapeutic potentials of combining chemotherapy with human papillomavirus (HPV) E7 subunit vaccines in an animal tumor model and to determine the underlying therapeutic mechanisms. EXPERIMENTAL DESIGN: Animals bearing HPV E6/E7-expressing tumors were treated intratumorally with a selected cytotoxic drug, cisplatin, twice at 1-week interval and s.c. with E7 subunit vaccines thrice at 1-week interval. Tumor chemoimmunoresponse was measured by tumor size. Ag-specific CTL activities and tumor histology were checked in mice under treatments. Apoptosis, in vivo T-cell subset depletion, adoptive CTL transfer, and tumor regression were used to determine the mechanisms for antitumor therapeutic effects. RESULTS: Combined therapy using cisplatin plus E7 subunit vaccines improved cure and recurrence rates of tumors and long-term antitumor immunity dramatically more than single therapy alone. In particular, both components of E7 subunit vaccines were required for induction of Ag-specific CTL as well as therapeutic synergy when combined with cisplatin. This therapeutic synergy was abrogated by depletion of CD8(+) T cells in vivo and was concomitant with histologic changes (such as heavy infiltration of lymphocytes and reduced tumor cell density). Finally, the increased sensitivity of cisplatin-treated tumors to CTL-mediated killing was found to be responsible for therapeutic synergy. CONCLUSIONS: E7 subunit vaccines plus cisplatin mediate antitumor therapeutic synergy through the increased sensitivity of cisplatin-treated tumors to CTL-mediated killing. Moreover, E7-based therapeutic vaccines have the potential to improve chemotherapy in patients with cervical cancer.

Animals↗

PubMed2006

Identifying candidate subunit vaccines using an alignment-independent method based on principal amino acid properties.

Subunit vaccine discovery is an accepted clinical priority. The empirical approach is time- and labor-consuming and can often end in failure. Rational information-driven approaches can overcome these limitations in a fast and efficient manner. However, informatics solutions require reliable algorithms for antigen identification. All known algorithms use sequence similarity to identify antigens. However, antigenicity may be encoded subtly in a sequence and may not be directly identifiable by sequence alignment. We propose a new alignment-independent method for antigen recognition based on the principal chemical properties of protein amino acid sequences. The method is tested by cross-validation on a training set of bacterial antigens and external validation on a test set of known antigens. The prediction accuracy is 83% for the cross-validation and 80% for the external test set. Our approach is accurate and robust, and provides a potent tool for the in silico discovery of medically relevant subunit vaccines.

Algorithms↗

PubMed2005

Development of a subunit vaccine for infectious pancreatic necrosis virus using a baculovirus insect/larvae system.

Various attempts to develop a vaccine against infectious pancreatic necrosis virus (IPNV) have not yielded consistent results. Thus, at present, no commercial vaccine is available that can be used with confidence to immunize fry of salmon and trout. We generated a cDNA clone of the large genome segment A of an IPNV Sp strain and expressed all structural protein genes in insect cells and larvae using a baculovirus expression system. Green fluorescent protein was also coexpressed as a reporter molecule. High yields of IPNV proteins were obtained and the structural proteins self assembled to form virus-like particles (VLPs). We tested the immunogenicity of the putative VLP antigen in immersion vaccine experiments (two concentrations) in rainbow trout (Oncorhynchus mykiss) fry, and by intraperitoneal immunisation of Atlantic salmon (Salmo salar) pre-smolts using an oil adjuvant formulation. Rainbow trout were challenged by immersion using either the Sp or the VR-299 strain of IPNV two or three weeks post-vaccination, while Atlantic salmon were bath challenged with Sp strain after two months, after parr-smolt transformation. In the rainbow trout fry challenged two weeks post-immunization, cumulative mortality rates three weeks post challenge were 14 % in the fry that had received the highest dose versus 8 % in the control groups. No indication of protection was seen in repeated trials using a lower dose of antigen and challenge three weeks post-immunisation. The cumulative mortality rate of intraperitoneally immunised Atlantic salmon post-smolts four weeks post challenge was lower (56%) than in the control fish (77%), showing a dose-response pattern.

Animals↗

PubMed1998

Characterization of immune responses to experimental polyvalent subunit vaccines assembled in iscoms.

Immune responses to experimental polyvalent subunit vaccines assembled in a particulate adjuvant/delivery system, iscoms, are described. The fusion protein ZZ-M5 comprises structures of staphylococcal protein A (ZZ) and the Plasmodium falciparum malaria antigen Pf155/RESA (M5). MHC congenic mice were immunized with ZZ-M5 conjugated to iscoms containing human influenza virus antigen (flu ag, M5-flu-isc) or to iscom matrix (iscom particles without flu ag, M5-isc). Comparison of antibody and T-cell responses to M5-isc and M5-flu-isc demonstrated that the flu ag in M5-flu-isc exhibits carrier-related helper functions and that the assembly of immunogens in M5-flu-isc did not result in any apparent antigenic competition. In addition, assembly of ZZ-M5 and flu ag in iscoms induced an alteration of the IgG subclass profile of the antibody response to M5. The results suggest that assembly of immunogens in iscoms may be a useful approach to the design of subunit vaccines but that both quantitative and qualitative aspects of the immunogenic properties of such constructs should be scrutinized.

Amino Acid Sequence↗