Liposomal Influenza Vaccine

black triangle This trivalent liposomal influenza vaccine consists of purified influenza haemagglutinin inserted into a membrane of phosphatidylcholine and phosphatidylethanolamine. It contains 15microg of haemagglutinin per viral strain per dose. black triangle The vaccine is immunogenic in the elderly, in younger adults and in children and adolescents with or without cystic fibrosis. black triangle Seroconversion rates were significantly higher with the liposomal vaccine than with a subunit vaccine for 3 of 3 and 2 of 3 strains in 2 published studies. Seroconversion occurred in a significantly greater number of participants receiving the liposomal vaccine than in those receiving a whole virus vaccine for all 3 strains in 1 study. black triangle Seroprotection rates were significantly better with the liposomal vaccine than with a subunit vaccine for 2 of 3 and 1 of 3 strains in 2 trials, and greater than with a whole virus vaccine for 2 of 3 strains in 1 trial. black triangle In a study in children with cystic fibrosis, a single dose of the liposomal vaccine was reported to have greater immunogenicity than 2 half doses (statistical analysis not performed). black triangle Local adverse reactions such as pain at the injection site, local induration, redness and swelling are transient and usually mild. black triangle Liposomal influenza vaccine did not induce a mean antiphospholipid antibody response in elderly volunteers.     

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.     

Influenza virosomes supplemented with GPI-0100 adjuvant: a potent vaccine formulation for antigen dose sparing

Adjuvants can stimulate vaccine-induced immune responses and can contribute decisively to antigen dose sparing when vaccine antigen production is limited, as for example during a pandemic influenza outbreak. We earlier showed that GPI-0100, a semi-synthetic saponin derivative with amphiphilic structure, significantly stimulates the immunogenicity and protective efficacy of influenza subunit vaccine administered via a systemic route. Here, we evaluated the adjuvant effect of GPI-0100 on a virosomal influenza vaccine formulation. In contrast to influenza subunit vaccine adjuvanted with GPI-0100, virosomal vaccine supplemented with the same dose of GPI-0100 provided full protection of mice against infection at the extremely low antigen dose of 2 × 8 ng hemagglutinin. Overall, adjuvanted virosomes elicited higher antibody and T-cell responses than did adjuvanted subunit vaccine. The enhanced immunogenicity of the GPI-0100-adjuvanted virosomes, particularly at low antigen doses, is possibly due to a physical association of the amphiphilic adjuvant with the virosomal membrane. These results show that a combination of GPI-0100 and a virosomal influenza vaccine formulation is highly immunogenic and allows the use of very low antigen doses without compromising the protective potential of the vaccine.     

Immunogenicity and safety of the influenza A/H1N1 2009 inactivated split-virus vaccine in young and older adults: MF59-adjuvanted vaccine versus nonadjuvanted vaccine

Since initial reports in April 2009, the pandemic influenza A (H1N1) virus has spread globally. Influenza vaccines are the primary method for the control of influenza and its complications. We conducted a multicenter clinical trial to evaluate the immunogenicity and safety of H1N1 vaccine (Green Cross Co.) in young adults (18 to 64 years) and the elderly (≥ 65 years) using a two-dose regimen, with the doses administered 21 days apart. Three different regimens of hemagglutinin antigen were comparatively analyzed: 3.75 μg (MF59 adjuvanted) versus 7.5 μg (MF59 adjuvanted) versus 15 μg (nonadjuvanted) in young adults and 3.75 μg (MF59 adjuvanted) versus 7.5 μg (MF59 adjuvanted) in the elderly. In young adults, all three vaccine regimens met the European Agency for the Evaluation of Medicinal Products (EMA) criteria after the first dose. In the elderly, on day 21 after the first dose, the rates of seroprotection and seroconversion were significantly higher for the 7.5-μg dose of MF59 adjuvanted vaccine than for the 3.75-μg dose (58.0% versus 44.3% [P = 0.03] and 53.7% versus 37.2% [P < 0.01], respectively). After the second dose, the geometric mean titer (GMT) increment was blunted with a 15-μg dose of nonadjuvanted vaccine, whereas the GMT increased about 2-fold with MF59 adjuvanted vaccines. In conclusion, a single 7.5-μg dose of MF59 adjuvanted vaccine would have a practical advantage over a two-dose, 3.75-μg, MF59 adjuvanted vaccine priming schedule. Following a two-dose priming schedule, the increase in hemagglutinin inhibition titers was higher with MF59 adjuvanted vaccine than with nonadjuvanted vaccine.     

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.     

Intranasal immunization of ferrets with commercial trivalent influenza vaccines formulated in a nanoemulsion-based adjuvant

NB-1008 is a surfactant-stabilized soybean oil-in-water nanoemulsion (NE) adjuvant with influenza virus antigen incorporated into the NE by simple mixing. Intranasal administration of the antigen with NE adjuvant efficiently produces both mucosal and serum antibody responses as well as a robust cellular Th1 immune response. To demonstrate the adjuvant effect of the W₈₀5EC NE, a killed commercial influenza vaccine for intramuscular administration (Fluzone or Fluvirin) was mixed with the W₈₀5EC NE adjuvant and administered intranasally to naïve ferrets. After a single intranasal immunization, the adjuvanted influenza vaccine elicited elevated serum hemagglutination inhibition (HAI) geometric mean titers (GMTs) ranging from 196 to 905 for the three hemagglutinin (HA) antigens present in the vaccine, which are approximately 19- to 90-fold higher titers at 1/50 the standard intramuscular commercial nonadjuvanted influenza vaccine dose. Seroconversion rates of 67% to 100% were achieved against each of the three viral strains present. The adjuvanted nasal influenza vaccine also produced significant cross immunity to five other H3N2 influenza virus strains not present in the vaccine and produced sterile immunity after challenge with homologous live virus. No safety issues were observed in 249 ferrets receiving the adjuvanted influenza vaccine. These findings demonstrate the ability of W₈₀5EC NE to adjuvant nasally administered influenza vaccine and provide a basis for studying the intranasal W₈₀5EC-adjuvanted influenza vaccine in humans.     

Effects of Different Adjuvants in the Context of Intramuscular and Intranasal Routes on Humoral and Cellular Immune Responses Induced by Detergent-Split A/H3N2 Influenza Vaccines in Mice

Influenza A/H3N2 viruses have caused the most severe epidemics since 1968 despite current immunization programs with inactivated vaccines. We undertook a side-by-side preclinical evaluation of different adjuvants (Alum, AS03, and Protollin) and routes of administration (intramuscular [i.m.] and intranasal [i.n.]) for assessing their effect on the immunogenicity and cross-reactivity of inactivated split vaccines (A/H3N2/New York/55/2004). Humoral and T cell-mediated immune responses against the homologous virus and a heterologous drifted strain (A/H3N2/Wisconsin/67/2005) were measured in BALB/c mice at 2, 6, and 19 weeks postboost. The AS03- and Alum-adjuvanted i.m. vaccines induced at least an 8-fold increase over the nonadjuvanted vaccine in functional antibody titers against both the homotypic and heterotypic strains and low IgG2a and high IgG1 levels, suggesting a mixed Th1/Th2 response with a Th2 trend. The Protollin-adjuvanted i.n. vaccine induced the lowest IgG1/IgG2a ratio, which is indicative of a mixed Th1/Th2-type profile with a Th1 trend. This adjuvanted vaccine was the only vaccine to stimulate a mucosal IgA response. Whatever the timing after the boost, both hemagglutination inhibition (HAI) and microneutralization (MN) titers were higher with the AS03-adjuvanted i.m. vaccine than with the protollin-adjuvanted i.n. vaccine. Finally, the Alum-adjuvanted i.m. vaccine and the lower-dose Protollin-adjuvanted i.n. vaccine elicited significantly higher CD4⁺ Th1 and Th2 responses and more gamma interferon (IFN-γ)-producing CD8⁺ T cells than the nonadjuvanted vaccine. Our data indicate that the adjuvanted vaccines tested in this study can elicit stronger, more persistent, and broader immune responses against A/H3N2 strains than nonadjuvanted inactivated influenza vaccines.     

Assessment of Antigen-Specific and Cross-Reactive Antibody Responses to an MF59-Adjuvanted A/H5N1 Prepandemic Influenza Vaccine in Adult and Elderly Subjects

Preparedness against an A/H5N1 influenza pandemic requires well-tolerated, effective vaccines which provide both vaccine strain-specific and heterologous, cross-clade protection. This study was conducted to assess the immunogenicity and safety profile of an MF59-adjuvanted, prepandemic influenza vaccine containing A/turkey/Turkey/01/2005 (H5N1) strain viral antigen. A total of 343 participants, 194 adults (18 to 60 years) and 149 elderly individuals (≥61 years), received two doses of the investigational vaccine given 3 weeks apart. Homologous and heterologous antibody responses were analyzed by hemagglutination inhibition (HI), single radial hemolysis (SRH), and microneutralization (MN) assays 3 weeks after administration of the first vaccine dose and 3 weeks and 6 months after the second dose. Immunogenicity was assessed according to European licensure criteria for pandemic influenza vaccines. After two vaccine doses, all three European licensure criteria were met for adult and elderly subjects against the homologous vaccine strain, A/turkey/Turkey/1/2005, when analyzed by HI and SRH assays. Cross-reactive antibody responses were observed by HI and SRH analyses against the heterologous H5N1 strains, A/Indonesia/5/2005 and A/Vietnam/1194/2004, in adult and elderly subjects. Solicited local and systemic reactions were mostly mild to moderate in severity and occurred less frequently in the elderly than in adult vaccinees. In both adult and elderly subjects, MF59-adjuvanted vaccine containing 7.5 μg of A/Turkey strain influenza virus antigen was highly immunogenic, well tolerated, and able to elicit cross-clade, heterologous antibody responses against A/Indonesia and A/Vietnam strains 6 weeks after the first vaccination.     

Local and systemic antibody responses in high-risk adults given live-attenuated and inactivated influenza A virus vaccines.

Forty seropositive older adults with chronic diseases were vaccinated intranasally with either influenza A/California/10/78 (H1N1) (CR37) or influenza A/Washington/897/80 (H3N2) (CR48) virus. No clinically significant decrements in pulmonary function occurred postvaccination. Eight (62%) recipients of CR37 virus and 16 (59%) recipients of CR48 virus became infected with vaccine virus, as indicated by a fourfold rise in nasal wash immunoglobulin G (IgG) or IgA antibody titer, a fourfold rise in serum antibody titer, isolation of vaccine virus from nasal washings, or all of these. Within 2 years after cold-recombinant virus vaccination, 29 vaccinees received trivalent inactivated influenza virus vaccine parenterally. After inactivated virus vaccination, 23 (79%) vaccinees developed a fourfold rise in nasal wash or serum antibody titer to H1 antigen and 24 (83%) developed a fourfold rise in nasal wash or serum antibody titer to H3 antigen. Significantly more cold-recombinant virus vaccinees developed a fourfold rise in nasal wash IgA antibody to H1 or H3 hemagglutinin compared with inactivated virus vaccinees (17 [43%] versus 9 [17%], P = 0.01). We conclude that these cold-recombinant virus vaccines are safe and immunogenic in seropositive older high-risk adults and more often induced a nasal wash IgA antibody response than the inactivated virus vaccine.     

Superior protection provided by a single dose of MF59-adjuvanted whole inactivated H5N1 influenza vaccine in type 1 diabetic mice

Vaccination is the preferred strategy for the prevention of influenza virus infection. Both H5N1 subunit and split vaccines have shown poor immunogenicity in clinical trials thus far. Therefore, it is urgent to develop more immunogenic and antigen-sparing H5N1 influenza vaccines as well as safe and effective adjuvants for humans, especially for immunocompromised people such as patients with diabetes mellitus. In this study, the protective effect of an MF59-adjuvanted inactivated whole-virion H5N1 vaccine was investigated in a type 1 diabetic mouse model. Mice (both healthy and diabetic) were immunized with a single dose of the inactivated vaccine, alone or adjuvanted with MF59 or Al(OH)₃. After four weeks, mice were challenged with a lethal dose of H5N1 virus. Antibody responses, survival rates, lung virus titers and body weight changes were tested. The results showed that addition of MF59 or Al(OH)₃ to the vaccine enhanced the antibody responses in both healthy mice and diabetic mice, but the MF59-adjuvanted groups showed higher antibody responses than the Al(OH)₃-adjuvanted groups. The addition of MF59 or Al(OH)₃ to the vaccine led to a conversion of the immune response from a Th1-biased response to an enhanced mixed Th1/Th2 profile. The MF59-adjuvanted inactivated whole-virion H5N1 vaccine provided superior protection in type 1 diabetic mice to either the vaccine alone or the vaccine adjuvanted with Al(OH)₃.     

Increasing the immunogenicity of inactivated chitosan adjuvanted vaccine from A/California/7/09 (H1N1) strain and analyzing the antigenic specificity of this influenza virus strain

Addition of chitosan as an adjuvant to subunit vaccine from the swine origin influenza virus A/California/7/09 (H1N1) increases vaccine immunogenicity by 8-16 times and significantly enhances its protective potency. Single immunization with chitosan adjuvanted vaccine induced similar antibody titers as two immunizations with unadjuvanted vaccine. Chitosan stabilized the immunogenicity of subunit vaccine when stored at 4 degrees C. The antigenic specificity of the A/California/7/09 (H1N1) virus strain did not resemble substantially that of the human influenza strains A/Brisbane/59/07 (H1N1) and A/Solomon Isles/3/06 (H1N1), which are among the 2008/2009 and 2007/2008 seasonal influenza vaccines, respectively, as well as that of the human influenza H1N1 virus strains that circulated about 30 years ago.     

A Reduced-Dose Seasonal Trivalent Influenza Vaccine Is Safe and Immunogenic in Adult and Elderly Patients in a Randomized Controlled Trial

With the recent pandemic of influenza A (H1N1) and vaccine shortages, there has been considerable interest in developing influenza vaccines with reduced doses, allowing for increased production capacity. Here we report a prospective, randomized, double-blind, single-center clinical trial of a reduced-dose whole-virion inactivated, adjuvanted influenza vaccine in adult and elderly volunteers. A total of 234 subjects, including 120 adults (18 to 60 years of age) and 114 elderly subjects (>60 years of age) were enrolled to receive either 6 μg or the conventional 15-μg dose of seasonal trivalent influenza vaccines. The subjects were followed for safety analysis, and serum samples were obtained to assess immunogenicity by hemagglutination inhibition testing. The subjects developed antibody responses against the seasonal influenza A virus H1N1 and H3N2 strains, as well as the seasonal influenza B virus included in the vaccines. Single doses of 6 μg fulfilled licensing criteria for seasonal influenza vaccines. No significant differences in rates of seroconversion or seroprotection or in geometric mean titers were found between the two dosage levels. All adverse events were rare, mild, and transient. We found that the present reduced-dose vaccine is safe and immunogenic in healthy adult and elderly subjects and triggers immune responses that comply with licensing criteria.     

Mismatch between the 1997/1998 influenza vaccine and the major epidemic A(H3N2) virus strain as the cause of an inadequate vaccine-induced antibody response to this strain in the elderly

The success of influenza vaccination depends largely on the antigenic match between the influenza vaccine strains and the virus strains actually circulating during the season. In the past, this match has proved to be satisfactory in most seasons. In the 1997/1998 season, however, hemagglutination inhibition (HI) assays with ferret antisera indicated a considerable mismatch between the H3N2 vaccine component and the most prevalent epidemic influenza A(H3N2) virus. The results from antigenic analyses using pre- and postvaccination serum samples from volunteers of various ages, including residents of nursing homes who were more than 60 years of age, were in good agreement with the results obtained with ferret antisera. Homologous serum antibody responses to the H3N2 vaccine component as well as the cross-reactivity of the induced antibodies to the epidemic H3N2 strain, declined with increasing age of the vaccinees. As a consequence of these two effects, 84% of the vaccinees over 75 years of age did not develop HI antibody titers >/= 40 against the major H3N2 virus variant of 1997/1998, suggesting that they were not protected against infection with this virus variant. These findings support the current policy of the World Health Organization (WHO), which is to base worldwide influenza virus surveillance on results predominantly obtained by antigenic analyses of influenza virus isolates with ferret antisera in HI tests. If an antigenic mismatch is observed, the protective efficacy of the vaccine, especially for the elderly, may be insufficient. The observations also support the current policy to include the elderly in serologic efficacy trials.     

Comparison of the Immunogenicity and Safety of the Conventional Subunit,MF59-Adjuvanted,and Intradermal Influenza Vaccines in the Elderly

The influenza vaccination is known as the most effective method for preventing influenza infection and its complications in the elderly. Conventional subunit (Agrippal S1; Novartis), MF59-adjuvanted (Fluad; Novartis), and intradermal (IDflu15; Sanofi Pasteur) influenza vaccines are widely used throughout South Korea. However, few comparative studies evaluating the safety and immunogenicity of these vaccines are available. Prior to the beginning of the 2011-2012 influenza season, 335 healthy elderly volunteers randomly received one of three seasonal trivalent influenza vaccines, the conventional subunit, MF59-adjuvanted, or intradermal influenza vaccine. Serum hemagglutination-inhibiting antibody levels were measured at the time of vaccination and at 1 and 6 months after vaccination. Adverse events were recorded prospectively. A total of 113 conventional subunit, 111 MF59-adjuvanted, and 111 intradermal influenza vaccine volunteers were followed up during a 6-month postvaccination period. One month after vaccination, all three vaccines satisfied Committee for Medical Products for Human Use (CHMP) immunogenicity criteria for the A/H1N1 and A/H3N2 strains but not for the B strain. Compared with the subunit vaccine, the intradermal vaccine exhibited noninferiority, while the MF59-adjuvanted vaccine exhibited superiority. Furthermore, the MF59-adjuvanted vaccine was more immunogenic against the A/H3N2 strain than was the subunit vaccine up to 6 months postvaccination. The most common local and systemic reactions to the conventional subunit, MF59-adjuvanted, and intradermal influenza vaccines were pain at the injection site (7.1%, 10.8%, and 6.3%, respectively) and generalized myalgia (0.9%, 8.1%, and 5.4%, respectively). Local and systemic reactions were similar among the three vaccine groups. MF59-adjuvanted vaccine exhibited superior immunogenicity compared with a conventional subunit vaccine and had a comparable safety profile. For older adults, the MF59-adjuvanted vaccine is preferable for providing superior immunogenicity.     

The seasonal influenza vaccine Agriflu(®)

Seasonal influenza continues to have a large impact annually. Combined with pneumonia, influenza is the sixth leading cause of death in the USA, and vaccination has been the most important tool to prevent it. Agriflu(?) is an egg-derived, subunit, nonadjuvanted trivalent inactivated vaccine indicated for immunization to prevent disease caused by influenza virus subtypes A and B contained in the vaccine. Agriflu was approved in the USA by the US FDA on 27 November 2009, for those aged 18 years and older, to prevent disease caused by influenza virus subtypes A and B. Based on clinical trial evidence, Agriflu has been shown to be safe, with <1% serious adverse event rates, and immunogenic. It has been proven to be highly effective to prevent culture-confirmed influenza and, thus, is an alternative to previously licensed seasonal influenza vaccines. Besides Fluvirin(?), Agriflu is the only subunit vaccine available in the USA. Owing to the economic burden, morbidity and mortality caused by seasonal influenza, addition of new, safe and effective vaccines to the available tools, to reduce the impact of influenza, is of importance and benefit, especially in the face of the recent shortages of influenza vaccines.     

Systemic and local antibody responses in elderly subjects given live or inactivated influenza A virus vaccines.

Intranasal live attenuated cold-adapted (ca) influenza A/Kawasaki/9/86 (H1N1) reassortant virus and parenteral inactivated influenza A/Taiwan/1/86 (H1N1) virus were given alone or in combination to 80 ambulatory elderly subjects. An enzyme-linked immunosorbent assay was used to measure hemagglutinin-specific (HA) antibodies in serum and nasal wash specimens collected before vaccination and 1 and 3 months later. Serum immunoglobulin G (IgG) and nasal wash IgA HA responses were elicited in 56 and 20%, respectively, of 25 inactivated-virus vaccinees and in 67 and 48%, respectively, of 27 recipients of both vaccines but in only 36 and 25%, respectively, of 28 vaccinees given live virus alone. Inactivated virus, administered alone or with live virus vaccine, induced higher titers of serum antibody than did the live virus alone. In contrast, nasal IgA HA antibody was elicited more often and in greater quantity by the vaccine combination than by either vaccine alone. Despite these differences, the peak titers of local antibody mounted by each group of vaccinees were similar. By 3 months postvaccination, serum IgG and nasal IgA HA antibody titers remained elevated above prevaccination levels in 50 and 17%, respectively, of the inactivated-virus vaccinees and in 46 and 23%, respectively, of recipients of both vaccines but in only 19 and 7%, respectively, of the live-virus and systemic antibodies, if vaccinees. The finding that live ca influenza A virus induced short-lived local and systemic antibodies, if confirmed, suggests that live virus vaccination may not be a suitable alternative or adjunct to inactivated virus vaccination for the elderly.     

Immunogenicity and effect of a virosomal influenza vaccine on viral replication and T-cell activation in HIV-infected children receiving highly active antiretroviral therapy

In order to evaluate the immunogenicity and the effect of a virosomal influenza vaccine on viral replication and T-cell activation in HIV-infected children receiving highly active antiretroviral therapy (HAART), 29 children infected with HIV-1 vertically (19 primed with a previous influenza vaccination and 10 who were not been immunized against influenza) were immunized with an intramuscular virosome-adjuvanted influenza vaccine. According to the European Agency for Evaluation of Medical Products (EMEA) criteria, the immunogenicity of the vaccine was adequate against all three influenza strains (A H1N1, A H3N2, and B) in the primed children, and against A H1N1 and A H3N2 in the unprimed children. After in vitro stimulation with vaccine antigens, the IFN-gamma levels in the peripheral blood mononuclear cells cultures increased significantly from a baseline level of 103.0 +/- 229.8 pg/ml to a 30-day level of 390.7 +/- 606.3 pg/ml (P < 0.05), with concentrations significantly higher (P < 0.05) in the primed children than in the unprimed children. No increase in plasma HIV-1 RNA or HIV-1 proviral DNA was observed in either subgroup, and the immunophenotype analyses demonstrated that the CD4+ cell counts and percentages, the CD4/CD8 ratio and activated lymphocytes remained stable in either group from baseline to 1 month after each vaccine dose. This study showed that the virosomal influenza vaccine does seem to be immunogenic in the majority of HIV-infected children receiving HAART and does not induce viral replication or T-cell activation. Given the possible influenza-related complications in children infected with HIV, these results support the use of this influenza vaccine in such patients.     

The investigation of the safety,genetic stability and immunogenicity of live influenza vaccine for adults in vaccination of 3-6 years old children

The study of the based on the A/Leningrad/134/17/57/(H2N2) attenuated adult live influenza vaccine (LIV) investigated features for immunization of the children, aged 3-6 years. During autumn, 1999, out of 256 children, aged 3-6 years, residents of the Leningrad region, who attended the kindergarten, 184 children were immunized with 1 or 2 doses of the live influenza vaccine, and 72 ones were given placebo. There were no any moderate or strong temperature reactions revealed after the inoculation. The LIV was shown to be genetically stable. After a single dose of the vaccine seroconversion to influenza type A virus and to influenza type B virus was observed respectively in 58% and in 39% of seronegative 3-6 year old vaccinees. The twofold LIV administration failed to give any advantages in stimulation of the immune response. During 6 months after immunization the morbidity rate in vaccinees did not exceed the morbidity rate in unvaccinated children. Thus LIV for adults proved safe and immunogenic and can be recommended for single dose immunization both of adults and children.     

Immunological potency of a subunit influenza vaccine in adults

Summary The immunological potency of a subunit influenza vaccine (from A/England/42/72 virus) and of two commercial whole-virus vaccines (containing either A/England/42/72 or A/Hong Kong/68 virus) was studied in adults in an industrial plant. Serum samples were taken in vaccinated and control non-vaccinated subjects prior to and three weeks and five months after the vaccination. Most of the vaccinees developed high levels of hemagglutination inhibiting antibodies against all the type A influenza viruses employed in the test; these antigens included a new strain (A/Dunedin/73) that had not previously circulated in Czechoslovakia. The antibody response after the subunit vaccine was somewhat better than after the whole-virus vaccines administration. The whole-virus vaccine from the A/England/42/72 virus was more efficient in inducing antibody response against the more recent isolates than the A/Hong Kong/68 virus vaccine.     

Impact of influenza vaccine formulation with a detailed analysis of the cytokine response

Vaccination provides the most effective method of limiting the impact of influenza. Inactivated influenza vaccines are available in three formulations and more information needs to be generated on how antigen presented in different vaccine formulations influences the subsequent immune response. In the present study, we have investigated the effect of two different influenza vaccine formulations on the resulting antibody and cytokine responses and compared these responses with influenza infection. Mice were vaccinated intramuscularly with one or two doses of whole or split virus vaccine or alternatively intranasally infected with influenza virus. Lymphocytes were isolated from spleen cells and stimulated in vitro for 24 or 72 h for analysis of cytokine profile at the gene expression and at the protein level. Additionally, whole blood was collected and the serum antibody response investigated by haemagglutination inhibition (HI) and enzyme-linked immunosorbent assay (ELISA). We found that one dose of whole virus vaccine induced higher antibody and cytokine responses and thus was more immunogenic in unprimed mice than split virus vaccine. Whole virus vaccine induced a strong IFN-gamma (type 1) immune response after one dose of vaccine and a more mixed cytokine response after the second dose. Split virus vaccine induced a type 2 response, particularly after two vaccine doses. Our results show that two doses of vaccine (both vaccine formulation) were more effective in induction of Th2 type of cytokines and thus indicate that both the formulation and also the number of vaccine doses substantially influences the magnitude and quality of the immune response.