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PubMed1981

Protection against feline leukemia by vaccination with a subunit vaccine.

An effective vaccine against feline leukemia virus infection has been developed by the collection and concentration of tissue culture medium harvested from a tumor cell line. Lymphoid cells were grown to near saturation density in a normal growth medium and then transferred to a serum-free medium. The serum-free medium was collected, concentrated, and evaluated for its vaccine potential. Cats receiving the vaccine emulsified in complete Freund adjuvant developed high antiviral and antitumor titers and were protected (81%) against virus challenge. Cats receiving the vaccine without an adjuvant developed lower antibody levels and lower protection (53%) from viremia. Age-matched and litter-matched controls developed no antibody to test antigens before the challenge, and 100% became persistently viremic after the challenge. Vaccination with the soluble tumor cell antigen vaccine proved successful in preventing the induction of feline leukemia virus infection.

Adjuvants, Immunologic↗

PubMed1993

[Tolerance of preventive influenza vaccination with a subunit vaccine].

The frequency and intensity of undesirable side effects after protective vaccination against influenza with a commercially available vaccine were studied. 82 gainfully employed persons of both sexes were questioned in respect of local reactions such as weal and flare reactions, itching, sensation of heat, tenderness on pressure, and impeded movement, as well as systemic reactions e.g. elevated temperature or fever, profound sweating, headache, malaise, and insomnia. In 61 of 82 questioned persons local reactions occurred within 24 hours after vaccination, mainly weal and flare reactions and tenderness on pressure. 10 persons had systemic reactions, chiefly headache and fever, 39 of the questioned persons who reported on undesirable effects considered these impairments to be slight, whereas 28 of the group did not feel that the impairments disturbed or upset them in any way.

Adult↗

PubMed1978

A/New Jersey/76 influenza vaccine trial in seronegative schoolchildren: comparison of a subunit vaccine with a whole-virus vaccine.

In the present vaccination trial, 202 seronegative schoolchildren comprising both sexes and aged 11 to 12 years were vaccinated i.m. in the upper arm with either the subunit vaccine at a dosage of 600 CCA or 200 CCA or with a whole-virus vaccine at a dosage of 200 CCA, using the double-blind procedure. Both vaccines were prepared from the strain A/New Jersey/76 (x 53a-recombinant). The vaccination was followed four weeks later by a booster injection. In tests of local and systemic reactogenicity, it was found that at both dosages the subunit vaccine caused a low frequency of minor adverse reactions. The whole-virus vaccine was marked by a significantly higher rate of adverse reactions, whether of the local or systemic variety. The whole-virus vaccine had, however, a higher immunogenicity than the subunit vaccine, and due to the relatively high rate of adverse reactions it causes, it is not recommended for the vaccination of seronegative children. Because of its low reactogenicity, the subunit vaccine can be given at higher dosage, and it is a matter for consideration whether a better antibody response might not result from two booster injections.

Antibodies, Viral↗

PubMed1998

Immunity provided by haemorrhagic septicaemia-subunit vaccine in ruminants.

A subunit vaccine against haemorrhagic septicaemia (HS), the principal killer disease in ruminants, especially cattle and carabao, in the Philippines, has been developed. Using capsules of Pasteurella multocida Group B as an active component of the vaccine, it gave solid protection against challenge with live organism in mice. An active calf protection test showed that in 24 hours, animals vaccinated with plain saline died after challenge compared to those given the subunit vaccine which survive the challenge dose. Using 104 cattle from a farm, the field trial of the HS subunit vaccine showed that the antibody titre was high for up to 14 months. A high titer is an indication of protection.

Animals↗

PubMed1978

[A new influenza subunit vaccine: hemagglutinating antibodies one year after vaccination (author's transl)].

The antibody response to a new influenza subunit vaccine was compare d one year after vaccination with the responses induced by two other influenza vaccines. The subunit vaccine was given either in a high dose form containing 2100 IU, or in a low dose form containing 700 IU. As comparison a split vaccine was used containing 800 IU and AI(OH)3 as adjuvant and a whole virus vaccine containing 2100 IU. Of the 399 vaccinated subjects which had taken part in this study 151 were available for hemagglutination inhibiting (HAI) antibody determinations one year after vaccination. Protection rates assessed for the respective groups on the assumption that serum HAI titers of 1 : 32 or greater confer protection. With the high dose of subunit vaccine 85% of volunteers were considered still to have protective titers one year after vaccination, compared with 77% of those who received the whole virus vaccine. Although the high dose subunit vaccine and whole virus vaccine induced similarly high protective levels lasting at least one year, the reactions observed on vaccination were significantly less with the subunit preparation. The lower dose of subunit vaccine induced lower levels of protection (60%) after one year, and lower mean HAI titers than the high dose subunit vaccine. Nevertheless protection was superior to that of the split virus adjuvant vaccine. The addition of adjuvant thus does not seem materially to improve the immune response to influenza virus antigens. An increase of antigen content can however be seen as a practical alternative for achieving higher antibody levels. The subunit vaccine would appear to be particularly suitable in this respect as even with a higher dose there is no increase in reactogenicity.

Adjuvants, Immunologic↗

PubMed1993

A human respiratory syncytial virus (RSV) primate model of enhanced pulmonary pathology induced with a formalin-inactivated RSV vaccine but not a recombinant FG subunit vaccine.

Human respiratory syncytial virus (RSV) is the leading cause of severe bronchiolitis and pneumonia in infants. RSV vaccine development has been stifled for the past 23 years because infants vaccinated with formalin-inactivated (FI) RSV have experienced exacerbated disease upon RSV infection. This exacerbated disease phenomenon is poorly understood, in part because of the lack of a primate model that exhibits a similar exacerbated disease state. Vaccination of African green monkeys with either FI RSV or a genetically engineered subunit vaccine termed FG glycoprotein reduced replication of challenge virus. However, only vaccination with FI RSV induced an enhanced pulmonary pathologic response to RSV infection. Pulmonary inflammatory scores in the FG glycoprotein-vaccinated monkeys were no greater than in monkeys vaccinated with adjuvant alone. This is the first demonstration of RSV vaccine-induced enhanced pathology in a primate and illustrates that a subunit vaccine has the potential of circumventing this exacerbated disease phenomenon.

Animals↗

PubMed1992

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

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)

Animals↗

PubMed1996

Rotavirus subunit vaccines.

We evaluated rotavirus subunit vaccines for use in humans and animals. Insect cells were co-infected with combinations of individual baculovirus recombinants expressing human, bovine or simian rotavirus VP2, VP4, VP6 or VP7 to produce virus-like particles (VLPs). To determine whether immunization with VLPs could induce active protective immunity, VLPs were administered parenterally to rabbits, and the immune response and protection from rabbit ALA rotavirus challenge were evaluated. Complete or partial protection was attained, showing that parenteral immunization with VLPs induces active protective immunity. We also examined whether heterotypic immune responses could be induced with a limited number of broadly reactive VP7 proteins or with chimeric particles (multiple VP7 types on individual particles). The feasibility of this approach was determined by immunizing mice with VLPs containing a G3 VP7 or G1 VP7 and chimeric G1/G3 VLPs. Broadly reactive neutralizing antibody was induced by the G1 VLPs. VLPs also have been successfully used to boost lactogenic (colostral and milk) immunity in dairy cows. Taken together, these results show that VLPs can be effective immunogens in rabbits, mice and dairy cattle when administered parenterally, a limited number of VLPs may be sufficient to produce a broadly protective vaccine, and G3 VLPs may serve as an effective subunit vaccine for use in bovines.

Animals↗

PubMed1983

Clinical reactions and antibody responses to influenza vaccines. A comparison of split or subunit vaccines in children and young adults.

The reactogenicity and immunogenicity of a trivalent split-product influenza vaccine and a trivalent subunit influenza vaccine were studied in 67 children and young adults. Subjects received two doses of either vaccine given one month apart. The reactogenicity of the two vaccines was similar. After the second dose of the split-product vaccine, the prevalence of hemagglutination-inhibiting (HAI) antibody titers of 20 or more was as follows: A/Brazil/78, 73%; A/Bangkok/79, 100%; and B/Singapore/79, 73%. Similar data for the subunit vaccine recipients were 78%, 100%, and 74%, respectively. The HAI antibody responses to the A/Brazil/78 and B/Singapore/79 antigens of both vaccines were relatively poor in those subjects who were initially seronegative (HAI antibody titer less than 5) to the specific antigen.

Adolescent↗

PubMedDate not supplied

An inactivated gE-negative marker vaccine and an experimental gD-subunit vaccine reduce the incidence of bovine herpesvirus 1 infections in the field.

An inactivated glycoprotein E-negative vaccine and an experimental glycoprotein D-subunit vaccine against bovine herpesvirus 1 (V1) were examined for their effectiveness in a randomized, double-bline, placebo-controlled field trial comprising 130 dairy farms. The use of these marker vaccines enabled us to monitor the incidence of infections in vaccinated populations. The aims of this trial were to evaluate whether these vaccines: (1) reduce the proportion of outbreaks in dairy herds; and (2) reduced virus transmission within dairy herds and to what extent. Vaccination with either of the two vaccines significantly reduced the proportion of herds wherein an outbreak occurred as well as the virus transmission within herds, as compared to placebo-treated herds. The estimated number of secondary cases caused by one infectious animal, expressed as the reproduction ratio R, was for both vaccines significantly > 1. This indicates that when BHV1 is introduced into vaccinated herds, major outbreaks may still occur.

Animals↗

PubMed1994

Respiratory syncytial virus-specific cell-mediated immune responses after vaccination with a purified fusion protein subunit vaccine.

Vaccination with a respiratory syncytial virus (RSV) fusion protein subunit vaccine (PFP-2) was done to determine if this vaccine induced evidence of cell-mediated immunity to RSV and if cell-mediated immunity prevented RSV reinfection. Healthy children 12-18 months old received 50 micrograms of PFP-2 or a saline control. Lymphocyte transformation (LTF) responses were determined before and 1 and 6 months after vaccination. PFP-2 induced positive LTF responses in 5 (83%) of 6 subjects whose prevaccination samples lacked evidence of cell-mediated immunity. Positive LTF responses in prevaccination samples were not boosted but were more persistent in vaccinees than in controls. Positive LTF responses were not associated with protection against subsequent infection. Immunization with PFP-2 induces correlates of cell-mediated immunity, but this immunity does not appear to be a critical component of protection.

Double-Blind Method↗

PubMed2001

Increased immunogenicity of the MF59-adjuvanted influenza vaccine compared to a conventional subunit vaccine in elderly subjects.

Three-hundred and eight outpatient elderly subjects (> or = 65 years) were randomly assigned to receive the MF59-adjuvanted influenza vaccine (FLU-AD; n = 204) or a conventional subunit influenza vaccine (AGRIPPAL S1; n = 104) in order to compare the safety and immunogenicity of the two vaccines. Although mild pain at the injection site was reported more frequently by subjects immunised with the adjuvanted vaccine, both vaccines were shown to be safe and well tolerated. The adjuvanted vaccine was more immunogenic as indicated by higher post-immunisation geometric mean titres (GMTs) and by higher proportions of subjects with post-immunisation > or = four fold increases of antibody titres or subjects with > or = 1/160 post-immunisation HI titres. These differences, statistically significant for all three strains after immunisation, indicated that, by addition of the MF59 adjuvant emulsion, conventional subunit influenza antigens acquire an enhanced immunogenicity without any clinically significant increase of their reactogenicity.

Adjuvants, Immunologic↗

PubMed2002

Influence of maternal antibodies on efficacy of a subunit vaccine: transmission of classical swine fever virus between pigs vaccinated at 2 weeks of age.

This study shows the effectiveness of vaccination with an E2 subunit vaccine against classical swine fever (CSF) in 2-week-old piglets. Half of the piglets were carrying maternally derived antibodies (MDAs) at the time of vaccination. Three and 6 months later, antibody levels were compared between the two treatments. Moreover, reduction of virus transmission was investigated at 3 and 6 months by doing transmission experiments. The vaccine was found to be capable of reducing virus transmission significantly at both time intervals. Maternal immunity reduced vaccination-induced antibody levels after 3 and 6 months and possibly led to a less effective protection against virus transmission after 6 months.

Animals↗

PubMed1987

Vaccination of rabbits with a bovine herpesvirus type 1 subunit vaccine: adjuvant effect of ISCOMs.

Bovine herpesvirus type 1 has two major immunogenic surface glycoproteins: a 90 kDa haemagglutinin and the 130 (74 + 54) kDa glycoprotein. These proteins were purified by rate zonal sucrose density gradient centrifugation after extraction with nonionic detergent Triton X-100. For the preparation of ISCOMs, the glycoproteins were further adsorbed during a second rate zonal centrifugation, to micelles of Quil A glycoside, already added to the gradient. Haemagglutinating peaks were collected and used as subunit vaccine in rabbits: groups of three animals were injected with 50, 10 and 5 micrograms protein. Seroconversion was followed by ELISA, haemagglutination inhibition, neutralizing and plaque reduction assays. ISCOMs and unadsorbed subunits were efficient in inducing neutralizing as well as haemagglutination inhibiting antibodies: ISCOMs gave a higher level of response. The efficiency demonstrated by ISCOMs suggests their potential as a subunit vaccine.

Adjuvants, Immunologic↗

PubMed1981

Immunogenicity of influenza A/USSR (H1N1) subunit vaccine in unprimed young adults.

Purified subunit vaccines (HANAflu) containing 20 microgram hemagglutinin of influenza A/USSR/90/77 (H1N1) alone or with 1-5% whole virus were compared to commercially available vaccines for reactogenicity and immunogenicity in unprimed young adults. Reactions to all vaccines were minimal. Sera from volunteers who received two intramuscular doses of vaccine or placebo were tested by hemagglutination-inhibition and neutralization tests. HANAflu with 1 microgram (5%) whole virus added was not different in immunogenicity from commercial vaccine. Both commercial vaccine and HANAflu with 1 microgram whole virus added gave higher seroconversion rates and more neutralization titers greater than or equal to 4 log2 than HANAflu alone and HANAflu + 0.2 microgram (1%) whole virus. Thus, the HANAflu subunit vaccine alone was less immunogenic than commercial vaccine in unprimed persons. However, addition of 1 microgram (5%) whole virus, but not 0.2 microgram (1%), eliminated this difference, There may be a role for addition of small amounts of whole virus to subunit influenza vaccines to overcome lower immunogenicity in unprimed populations.

Adolescent↗

PubMed1976

[Field trial with a new type of influenza subunit vaccine (author's transl)].

In a field trial a new influenza subunit vaccine was tested in parallel with a vaccine prepared from the whole virus. The subunit vaccine essentially contained only the proteins of the viral envelope, haemagglutinin and neuraminidase, which had been selectively solubilized by treatment with cetyl trimethylammonium bromide. Both vaccines contained 700 IU of strain A/Port Chalmers/73 in 0.5 ml. They were given to volunteers by the subcutaneous route with and without the addition of Al (OH)3 as adjuvant. Blood samples were taken on days 0, 28 and 90. Development of antibodies was assayed in the haemagglutination-inhibition (HI) and neuraminidase-inhibition (NI) test. All vaccines exhibited a very good immunogenic effect as judged from the number of volunteers with at least a four-fold rise in antibodies in the HI-test and those reaching titres that are considered to be sufficiently high for protection against disease. The best results were obtained with the aqueous subunit vaccine. All four vaccines also stimulated the formation of neuraminidase-inhibiting antibodies. The vaccines were well tolerated by the volunteers. The incidence of minor local reactions such as redness, swelling and pain varied according to the vaccine used, as shown on statistical evaluation. The aqueous subunit vaccine clearly proved to be superior in this respect.

Adolescent↗

PubMed1998

Efficacy of vaccination for Mycobacterium avium with whole cell and subunit vaccines in experimentally infected swine.

Mycobacterium avium infections are a common problem in large swine producing states and cause substantial financial losses at slaughter inspection due to carcass condemnation. Once the infection is established in a swine herd it is difficult to effectively prevent or eliminate the disease. Previous mouse studies in our laboratory suggested that Macrophage Inhibitory Factor-A3 (MIF-A3) is a virulence factor of M. avium and potential antigen for vaccine development. In this study we evaluated the efficacy of a killed 'whole cell' M. avium serovar 2 bacterin and conjugated MIF-A3 subunit vaccine in preventing infection and disease in swine challenged with virulent M. avium serovar 2. Gross and microscopic pathology, acid-fast staining, culture and polymerase chain reaction (PCR) for the M. avium specific insertion sequence IS902 were utilized in evaluation. Results indicated that neither vaccine prevented infection in challenged animals; however, a 47% reduction in severity of disease was found in swine vaccinated with the 'whole cell' M. avium serovar 2 bacterin. Reduction in severity of disease was not detected in animals vaccinated with the subunit MIF-A3 vaccine.

Animals↗

PubMed2005

An oral delivery system for recombinant subunit vaccine to fish.

Oral vaccination is considered as the most desirable method for immunizing fish because it is non-stressful, user-friendly and is capable of easy administration to large numbers of fish. However, many publications have indicated that the current oral vaccines still lack the desired efficacy. Here we reported on an oral vaccine method to deliver recombinant subunit vaccine based on the food chain of fish, in that live Artemia nauplii are encapsulated with recombinant bacteria containing the antigen. The feasibility and efficacy of this method for delivering protein antigen was tested in a zebrafish model, where immunisation took place through feeding Artemia encapsulated with recombinant E. coli. By this oral vaccine method the antigen could be delivered to the hindgut as confirmed by immuno-histochemistry, and its efficacy was demonstrated by the ability to protect vaccinated fish significantly from a direct injection of a native Pseudomonas exotoxin and bacterial pathogen. Combined with the recombinant technology for producing desired protein antigens, this oral vaccine delivery method provides the capacity to deliver a variety of different antigens, including the option for delivery of multivalent vaccines by the oral route.

Administration, Oral↗