Virosomal Vaccine Research Articles

Virosomal influenza vaccine: a safe and effective influenza vaccine with high efficacy in elderly and subjects with low pre-vaccination antibody titers

Virosomal influenza vaccine: a safe and effective influenza vaccine with high efficacy in elderly and subjects with low pre-vaccination antibody titers

Rapid antibody response after vaccination with a virosomal hepatitis a vaccine.

This study was designed to assess the early antibody kinetics after a priming dose, and the extent of the antibody increase after a booster dose of an inactivated virosomal hepatitis A virus (HAV) vaccine (Epaxal). This was an open, uncontrolled study in 30 healthy subjects. The vaccine was injected intramuscularly on day 1 and month 12. Serum antibody titers were measured by ELISA on day 1 (pre dose) and at various time points thereafter until month 12 (pre-booster dose). After the booster dose, antibody titers were measured at various intervals until month 24. Neutralizing antibody titers were measured in 12 subjects a number of times during the 1st month by an antibody neutralization assay. Titers > or = 10 mIU/ml were considered seroprotective. ELISA antibody titers showed a rapid increase post vaccination. By day 15, 96% of subjects were seroprotected, which increased to 100% by day 22 (n = 27 evaluable subjects, aged 18-43 years; 13 male, 14 female). All subjects achieved seroprotective HAV-neutralizing antibody titers by day 11 (n = 12). The booster vaccination at month 12 resulted in a strong response in all subjects, with a sustained anti-HAV antibody titer (1,155 mIU/ml) at month 24. Both the priming and booster doses were well tolerated. Primary vaccination with this virosomal HAV vaccine is well tolerated and induces a rapid HAV-neutralizing antibody response resulting in seroprotection in all subjects within 10 days. In addition, the booster vaccination results in prolonged seroprotective antibody levels.

Virosomal influenza vaccine: a safe and effective influenza vaccine with high efficacy in elderly and subjects with low pre-vaccination antibody titers

In 14 clinical studies, various efficacy and safety aspects of a new virosomal influenza vaccine (Invivac ®) were assessed in 2865 subjects. The virosomal influenza vaccine fully complies with the Committee for Proprietary Medicinal Products (CPMP) requirement for immunogenicity of influenza vaccines. In particular, in a subset of subjects with low pre-vaccination titers (thus those persons who actually need protection by a vaccine), between 76 and 99% of subjects (dependent on age, health status and vaccine components) achieved protective hemagglutination inhibiting (HI) antibody titers after vaccination with the virosomal influenza vaccine. Acceptable frequencies of well-known local and systemic reactions were observed in healthy adults and risk subjects in clinical studies and in a post-marketing study population. These reactions were transient and generally not severe, and did not cause major inconvenience. In conclusion, Invivac ® is an efficacious and safe vaccine for the protection against influenza in healthy and chronically ill adult subjects. The vaccine is especially efficacious in subjects with low pre-vaccination immunity.

Development of a virosome vaccine against avian metapneumovirus subtype C for protection in turkeys.

An avian metapneumovirus (aMPV) virosome vaccine was prepared and tested for protection of turkeys by aMPV challenge. The vaccine was produced using a detergent-based (Triton X-100) extraction of aMPV subtype C followed by detergent removal with SM2 Bio-Beads. Western blot and virus-neutralization analysis confirmed that the aMPV virosomes contained both the fusion and attachment glycoproteins. Specific-pathogen-free turkeys were immunized either intranasally (i.n.) or intramuscularly (i.m.) with two doses of the aMPV virosome vaccine. Vaccination decreased clinical signs of disease following virulent challenge, and IN vaccination was superior to i.m. vaccination in reducing clinical signs. Decreases in viral load in the respiratory tract were observed in turkeys receiving i.n. vaccination with aMPV virosomes compared to unvaccinated poults. Increased virus-neutralizing antibody levels against aMPV were observed in birds vaccinated with virosomes. These results demonstrate that immunization of turkeys with aMPV virosomes can be an effective strategy for control of disease.

An update on the prevention of influenza in children and adolescents.

Influenza virus types A and B cause yearly outbreaks of respiratory tract infections in all age groups including children and adolescents. Complications, such as high fever, febrile convulsions, secondary bacterial infections and myositis frequently lead to hospitalisation. Safe and effective split, subunit and virosome vaccines are available from 6 months of age onwards. Most European countries do have guidelines for the use of influenza vaccines and current strategies primarily aim at decreasing the burden of influenza disease in certain, heterogeneously defined high risk groups. unfortunately, compliance of many physicians and patients with immunisation recommendations is rather poor and several barriers to immunisation have been identified. These deserve our specific attention in the future. Recently, neuraminidase inhibitors with curative and preventive efficacy against influenza virus types A and B have become available. They serve as second line weapons for influenza prophylaxis under specific circumstances.

Mucosal antibody response induced with a nasal virosome-based influenza vaccine

A vaccination against influenza that elicits both a systemic antibody and a mucosal IgA response would improve on the protective efficacy of currently available vaccines. Previous studies have shown the safety and efficacy of virosomes as delivery systems in vaccination. This study was a controlled, randomised, double-blind, single centre, phase II trial assessing an intranasal virosome vaccine, adjuvanted with heat-labile toxin (HLT) from enterotoxigenic Escherichia coli, versus an intranasal without HLT and comparing it open to an intramuscular vaccine in a total of 88 healthy adults. The development of a new technique enabled for the first time the detection of neutralising IgA antibodies in very dilute nasal wash samples. It was demonstrated that intranasally administered inactivated influenza vaccine, adjuvanted with HLT, not only elicits a spectrum of humoral and cell-mediated responses in healthy adults, critical for the protection and recovery from influenza virus infection, but is also highly effective in eliciting IgA neutralising antibodies at the mucosa. Intranasal virosome-formulated, HLT-adjuvanted, influenza vaccine was effective and well tolerated in this study. Its potential to offer a high level of mucosal protection, not provided by conventional parenteral vaccination, could play a significant role in preventing morbidity and mortality associated with influenza.

Development of a virosome vaccine for Newcastle disease virus.

In an effort to protect chickens against Newcastle disease (ND), a nonreplicating virosome vaccine was produced by solubilization of Newcastle disease virus (NDV) with Triton X-100 followed by detergent removal with SM2 Bio-Beads. Biochemical analysis indicated that the NDV virosomes had similar characteristics as the parent virus and contained both the fusion and hemagglutinin-neuraminidase proteins. To target the respiratory tract, specific-pathogen-free chickens were immunized intranasally and intratracheally with the NDV virosome vaccine. This vaccine was compared with a standard NDV (LaSota) live-virus vaccine for commercial poultry. Seroconversion (> or = four fold increase in hemagglutination inhibition [HI] antibody titers) was achieved in all birds vaccinated with the virosome vaccine. Upon lethal challenge with a velogenic NDV strain (Texas GB), all birds receiving either vaccination method were protected against death. Antibody levels against NDV, as determined by enzyme-linked immunosorbent assay and HI titer, were comparable with either vaccine and increased after virus challenge. These results demonstrate the potential of virosomes as an effective tool for ND vaccination.

Effectiveness of influenza vaccination of children with recurrent respiratory tract infections in reducing respiratory-related morbidity within the households

To evaluate the effectiveness of influenza vaccination in reducing respiratory-related morbidity among children with recurrent respiratory tract infections (RRTIs) and their household contacts, 127 children aged 6 months–9 years (78 males; median age, 3.7 years) with a history of RRTIs (≥6 episodes per year if aged ≥3 years; ≥8 episodes per year if aged <3 years) were randomized to receive the intranasal virosomal influenza vaccine ( n=64 with 176 household contacts) or a control placebo ( n=63 with 173 household contacts). During influenza season, the vaccinated children had fewer respiratory infections, febrile respiratory illnesses, prescribed antibiotics and antipyretics, and missed school days than the controls, and similar benefits and a reduction in the loss of parental work were observed among their household contacts. This study shows that the benefits of influenza vaccination extend to children with RRTIs and their family members and encourages to recommend its use in such children.

Intranasal immunization against influenza.

Nasalflu is a novel influenza subunit vaccine, which is administered by the intranasal route using a spray device. Nasalflu is based on the virosomal concept which is registered in the EU as Epaxal Berna, a vaccine against Hepatitis A, and Inflexal Berna V, a subunit influenza vaccine. The virosome is a carrier system which delivers antigens to cells and is able to induce both B- and T-cell immunity. When virosomal vaccines are given parenterally, an immune response is elicited fast and sufficiently.

Immunogenicity and safety of a virosomal influenza vaccine in HIV-infected children

Immunogenicity and safety of a virosomal influenza vaccine in HIV-infected children

An open-label comparison of the immunogenicity and tolerability of intranasal and intramuscular formulations of virosomal influenza vaccine in healthy adults

Background: Many intramuscular inactivated influenza vaccines achieve suboptimal results in the prevention of respiratory disease and influenza complications. This has led to the current interest in developing effective oral or intranasal preparations. Objective: This study compared the immunogenicity and tolerability of intranasal and intramuscular formulations of virosomal subunit influenza vaccine in healthy adults. It also assessed the immunogenicity and tolerability of 3 different production lots of the intranasal vaccine containing Escherichia coli heat-labile toxin adjuvant. Methods: This was a multicenter, Phase I, randomized, open-label pilot study in which the primary end point was immunogenicity (hemagglutination-inhibition [HI] antibody assay on days 1 and 29). The secondary end point was the frequency of adverse events (AEs). Subjects were assigned to 4 vaccination groups: groups AI, AII, and AIII received intranasal influenza vaccine from batches that differed in the hemagglutinin and neuraminidase strains used, and group B received intramuscular virosomal subunit vaccine. Assessments of health status, hematology, biochemistry, body temperature, heart rate, blood pressure, and incidence of AEs were made on days 1, 8, and 29, and serology was assessed on days 1 and 29. Results: The study enrolled 88 subjects. All 3 production lots of intranasal vaccine induced an immune response to most of the viral strains administered (A/Singapore, A/Texas, A/Wuhan, B/Beijing), with no notable immunogenic differences between lots. After intranasal vaccination, geometric mean titers (GMT) increased 2.7-fold against A/Singapore (group AI); 1.8- and 3.1-fold against A/Texas (groups AII and AIII, respectively); 1.9- to 2.4-fold against A/Wuhan; and 1.5- to 1.7-fold against B/Beijing. After intramuscular vaccination, GMT increased 11.3-, 6.3-, and 2.7-fold against A/Texas, A/Wuhan, and B/Beijing, respectively. Seroprotection (HI antibody titers ≥1:40 in >70% of those vaccinated) was achieved against all strains in the group that received intramuscular vaccination, against A/Wuhan in all groups that received intranasal vaccination, and against A/Texas in group AII. Both vaccine formulations were well tolerated. Intranasal vaccination was associated with a low incidence (<20%) of nasal AEs. Conclusions: Both the intranasal and intramuscular vaccinations elicited a systemic immune response and were well tolerated. The different batches of intranasal vaccine showed a similar immunogenic profile. Intranasal administration may be preferred to intramuscular administration by some patients.

Comparison of three different influenza vaccines in institutionalised elderly

The reactogenicity and the humoral immune response to three influenza vaccines were evaluated in a randomised, double-blind trial at nursing homes in north-east Italy in winter 1998–1999. Of the 285 subjects, who completed the follow-up, 93 were administered virosomal vaccine, 99 received MF59-adjuvanted vaccine and 93 had split vaccine. Ten subjects (0.3%) reported local and/or systemic reactions in the first week after immunisation. After 4 weeks, protection rates (≥40) were near 100% for the H1N1 and B strain and 76.0% against H3N2. The MF59-adjuvanted vaccine group had higher geometric mean titres than the other two. However, the true clinical benefit of the new adjuvanted vaccine should be further substantiated by comparative protective studies. Our results suggest that immune response to influenza vaccination in institutionalised elderly is satisfactory.

Adjuvanted Influenza Vaccine

Adjuvanted influenza vaccine is composed of 2 type A and 1 type B inactivated influenza subunits combined with an oil-and-water emulsion (MF59). Each dose contains 15microg haemagglutinin per strain. Adjuvanted influenza vaccine was immunogenic in elderly vaccinees and in younger adults after 1 to 3 consecutive annual injections. According to studies available to date, the adjuvanted vaccine was more immunogenic than the nonadjuvanted subunit or split virus vaccines and the virosomal vaccine for 1 to 3 of the 3 strains tested per injection. The immunogenic effect generally persisted for longer after the adjuvanted vaccine than the nonadjuvanted subunit vaccine in elderly recipients. The adjuvanted vaccine also appeared to be more effective than the nonadjuvanted subunit vaccine against antigenically different heterovariant strains in elderly vaccinees. The 28-day seroprotection rate in 4 studies was significantly greater after the adjuvanted vaccine for 1 or 2 of the 3 strains tested compared with the nonadjuvanted subunit vaccine and the virosomal vaccine and for 1 of 3 strains compared with the split virus vaccine. The incidence of systemic adverse events was generally low. Local reactions such as pain, erythema and induration occurred more frequently with the adjuvanted than the 2 nonadjuvanted or the virosomal vaccines; however, these were mild and transient.

Immunopotentiating of mucosal and systemic antibody responses in mice by intranasal immunization with HLT-combined influenza virosomal vaccine

The mucosal vaccination strategy against influenza has been investigated by using influenza virosomal vaccine (IRIV) combined with two different adjuvants: the procholeragenoid (PCG) and the Escherichia coli heat labile toxin (HLT). A comparative study has been carried out on mice administered intranasally with these different formulations of influenza vaccine. PCG appears less effective than HLT in inducing an IgG response, but both the adjuvants elicit mucosal adjuvant activity inducing s-IgA in the upper respiratory tract. On the contrary, only HLT when administered intranasally to mice with influenza virosomes stimulates the production of s-IgA in the lower respiratory tract thereby providing a better protection against primary infection of the respiratory system. Both HLT and PCG enhance the production of IFN- γ in the respiratory tract, nevertheless HLT appears more efficacious as a mucosal adjuvant.

Safety and immunogenicity of intranasally administered inactivated trivalent virosome-formulated influenza vaccine containing Escherichia coli heat-labile toxin as a mucosal adjuvant.

A trivalent influenza virosome vaccine containing hemagglutinin and Escherichia coli heat-labile toxin (HLT) was administered intranasally to young adults and elderly subjects. Symptoms that followed immunization were mild and transient. A significant increase in serum hemagglutination inhibition (HI) antibody was noted for the 3 vaccine strains. There was no significant difference in postimmunization geometric mean titers or seroconversion rates between age groups. The percentage of subjects attaining protective HI titers (>/=40%) was comparable in both groups for the A/Bayern (P=.5) and B/Beijing (P=.3) strains but was higher among young adults (92.2%) versus elderly subjects (76.5%; P=.057) for the A/Wuhan strain. The proportion of subjects with nonprotective baseline titers who attained protective levels after immunization was similar in both age groups for the A/Bayern and B/Beijing components. For the A/Wuhan component, significantly (P=.017) more young adults achieved protective titers versus elderly subjects (85. 7% and 53.8%, respectively). Vaccination evoked a significant (P<. 005) increase in anti-HLT antibody titers.

Influenza vaccination in the elderly

Influenza vaccination of elderly people has been shown to be useful. All vaccine types are well tolerated by higher age group vaccinees. Actually, whole virus vaccine, split virus vaccine and subunit vaccine are used in the vaccination of the elderly. Some studies have suggested that the induction of serum influenza antibody production was reduced in elderly persons when compared with that elicited in younger persons. However, investigations on the protective efficacy of influenza vaccination in the elderly have demonstrated a clinical protection of ⩾ 50% for preventing hospitalization. Live attenuated influenza vaccine conferred protection similar to that obtained with a conventional subunit vaccine. A virosomal unilamellar trivalent hemagglutinin vaccine showed promising serological results compared with those obtained with a whole cell vaccine and with a subunit vaccine, respectively. The actual policy is to vaccinate persons ⩾ 65 years of age and the groups that can transmit influenza to them. Each year's vaccine should contain three virus strains representing the influenza viruses that are likely to circulate in the upcoming winter.

Immunogenicity of trivalent subunit versus virosome-formulated influenza vaccines in geriatric patients

The safety and immunogenicity of a commercial trivalent subunit influenza vaccine and an experimental virosome-formulated influenza vaccine were evaluated among geriatric patients in a double-blind, randomized manner. The virosome vaccine was produced by incorporating hemagglutinin (HA) into the membrane of liposomes composed of phosphatidylcholine. Both vaccines elicited a significant ( P < 0.01) rise in the geometric mean anti-HA antibody titer to all three vaccine components 1 month after immunization. However, significantly ( P < 0.005) more subjects vaccinated with the virosome preparation mounted a more than fourfold rise to the A/Singapore and A/Beijing strains compared with those who received subunit vaccine. The percentage of patients who attained protective levels (anti-HA titer ≥ 40) of anti-A/Beijing antibody was also significantly ( P < 0.005) higher in the virosome group. Subjects who possessed non-protective baseline antibody levels to the A/Singapore and A/Beijing strains were more likely ( P < 0.005–0.030) to achieve protective levels after immunization with the virosome vaccine than with the subunit vaccine. Of particular clinical significance was the fact that 68.4% of subjects immunized with the virosome vaccine attained protective levels of antibody to all three vaccine components versus 38% for the subunit vaccine ( P = 0.010).

Virosomal Hepatitis A Vaccine (Strain RG-SB)

Synopsis Virosomal hepatitis A vaccine contains formalin-inactivated hepatitis A (strain RG-SB) antigen adsorbed on to immunopotentiating reconstituted influenza virosomes (IRIVs). IRIVs act as an adjuvant and may stimulate both the cell-mediated and humoral immune responses to vaccine antigens. In noncomparative studies, virosomal hepatitis A vaccine (500 radioimmunoassay units) has exhibited immunogenicity in adults and children, inducing seroconversion in almost all volunteers within 4 weeks (usually within 2 weeks) of vaccination. Booster injections of the virosomal vaccine 12 months after the initial dose increased anti-hepatitis A virus (anti-HAV) antibody titres by 11- to 39- fold. Studies of up to 3 years in duration (with a booster vaccination after 1 year) have shown high anti-HAV antibody titres; protection against hepatitis A infection has been estimated to last for 8 to 12.5 years and an unpublished report suggests that 68% of vaccinees may be protected for ⩾30 years. In comparative studies, the virosomal vaccine produced lower anti-HAV antibody titres than an aluminium hydroxide-adsorbed vaccine (strain HM175), but similar percentages of volunteers seroconverted. The virosomal vaccine was shown to have 95% protective efficacy in unpublished preliminary results of a randomised double-blind trial involving Nicaraguan children. The vaccine had better local tolerability than an aluminium hydroxide-adsorbed hepatitis A (strain HM175) vaccine in immunogenicity studies. The most common adverse effect was pain or soreness at the injection site. Thus, virosomal hepatitis A vaccine (strain RG-SB) is highly immunogenic, has demonstrated protection from hepatitis A infection in a preliminary report, and appears to have a relatively low incidence of local adverse effects on injection. The final placement of this vaccine in the prevention of hepatitis A infection will be determined by the duration of protection it offers in comparison to other hepatitis A vaccines and its relative acquisition costs.

Preparation of influenza virosome vaccine with muramyldipeptide derivative B30-MDP

An influenza virosome vaccine, consisting of influenza hemagglutinin-neur-aminidase antigens (HANA), the muramyldipeptide derivative 6-O-(2-tetra-decylhexadecanoyl)-N-acetyl-muramyl-L-alanyl-D-isoglutamine (B30-MDP) and cholesterol, was prepared by the detergent removal method using a flow-through dialyzer, Liposomat. The shape of the influenza virosome vaccine mimicked that of the influenza virus, namely, B30-MDP/cholesterol vesicle covered with HANA spikes. The particle size and size distribution of prepared virosomes were evaluated by quasi-elastic laser light scattering and gel permea tion chromatography. The state of incorporation of HANA spikes at the membrane surface of virosome was confirmed by electron microscopy. The results indicated that virosome formation was influenced by initial B30-MDP concentration in the mixed micellar solution prior to dialysis. It is apparent that the initial concentration of B30-MDP, relative to the mixed-micelle-to-viro-some transition, is an important factor for virosome preparation. Accordingly, the transition was evaluated and clarified by the changes in membrane fluidity and particle size during the dialysis process. The results indicated that it is important to adjust the initial B30-MDP concentration in the mixed micellar solution before dialysis so that the concentration for the mixed-micelle-to-vesicle transition coincides with that for mixed-micelle-to-rosette transition appropriate for virosome formation.

A virosome vaccine antigen delivery system does not stimulate an antiphospholipid antibody response in humans

A virosome vaccine delivery system comprised of the hemagglutinin of influenza A virus incorporated into unilamellar liposomes consisting of phosphatidylethanolamine (PE) and phosphatidylcholine (PC) or only PC was developed. The anti-PE and anti-PC antibody response was determined for human volunteers immunized with a virosome-formulated vaccine against hepatitis A, or a standard or virosome-formulated influenza vaccine. None of the 100 young adults who received two doses of the hepatitis A vaccine 1 year apart mounted a significant (greater than fourfold) antiphospholipid antibody response. Immunization with a single dose of trivalent influenza vaccine engendered a significant anti-PC and anti-PE antibody response in 1 of 32 elderly nursing home residents who received the virosome-formulated influenza vaccine and in 1 of the 31 residents who received a commercial subunit vaccine. These findings indicate that the virosome system can potentiate the human immune response to vaccine antigens without a concomitant rise in antiphospholipid antibodies.