Types Of Influenza Vaccines Research Articles

Vaccines for Seasonal and Pandemic Influenza

Seasonal influenza continues to have a huge annual impact in the United States, accounting for tens of millions of illnesses, hundreds of thousands of excess hospitalizations, and tens of thousands of excess deaths. Vaccination remains the mainstay for the prevention of influenza. In the United States, 2 types of influenza vaccine are currently licensed: trivalent inactivated influenza vaccine and live attenuated influenza vaccine. Both are safe and effective in the populations for which they are approved for use. Children, adults <65 years of age, and the elderly all receive substantial health benefits from vaccination. In addition, vaccination appears to be cost-effective, if not cost saving, across the age spectrum. Despite long-standing recommendations for the routine vaccination of persons in high-priority groups, US vaccination rates remain too low across all age groups. Important issues to be addressed include improving vaccine delivery to current and expanded target groups, ensuring timely availability of adequate vaccine supply, and development of even more effective vaccines. Development of a vaccine against potentially pandemic strains is an essential part of the strategy to control and prevent a pandemic outbreak. The use of existing technologies for influenza vaccine production would be the most straightforward approach, because these technologies are commercially available and licensing would be relatively simple. Approaches currently being tested include subvirion inactivated vaccines and cold-adapted, live attenuated vaccines. Preliminary results have suggested that, for some pandemic antigens, particularly H5, subvirion inactivated vaccines are poorly immunogenic, for reasons that are not clear. Data from evaluation of live pandemic vaccines are pending. Second-generation approaches designed to provide improved immune responses at lower doses have focused on adjuvants such as alum and MF59, which are currently licensed for influenza or other vaccines. Additional experimental approaches are required to achieve the ultimate goal for seasonal and pandemic influenza prevention--namely, the ability to generate broadly cross-reactive and durable protection in humans.

Safety and Efficacy of Two Types of Influenza Vaccination in Heart Transplant Recipients: A Prospective Randomised Controlled Study

Influenza may cause severe disease in immunosuppressed patients. Different vaccines have been proved to be efficacious to prevent influenza in tranplant recipients. Since the last five years the addition of adjuvants to improve the immune response to vaccine preparations has been proposed and evaluated. In this study, two antigenically identical vaccines, but different for the presence of adjuvants were randomised among a cohort of heart transplant recipients to evaluate their safety and immunogenicity. 58 patients, receiving an heart transplant more than 6 months before, were randomised to receive one shoot vaccination with Fluad (containing the MF59 adjuvant) or Agrippal (no adjuvant added) or to enter the control, not-vaccinated, group. The immune response to influenza was evaluated separately for type A and type B viruses and for the IgG and the IgM antibodies. Patients were clinically evaluated at least monthly up to 6 months. Influenza symptoms were reported by 33% of patients receiving Fluad, 29% of the Agrippal and 63% of the control group. 4 episodes of acute myocardial rejection >/=3A were identified without difference between the three groups. The superior efficacy of vaccines containing adjuvants was not found and the data clearly confirmed that vaccination against influenza is safe and effective in heart transplant recipients. The use of vaccine containing adjuvant substances do not ameliorate the clinical performance of the immunisation suggesting that less expensive influenza vaccine preparation without adjuvant substances could be equally useful to protect heart transplant recipients.

Vaccines for preventing influenza in healthy adults.

Three different types of influenza vaccines are currently produced worldwide. None is traditionally targeted to healthy adults. Despite the publication of a large number of clinical trials, there is still substantial uncertainty about the clinical effectiveness of influenza vaccines and this has negative impact on the vaccines acceptance and uptake. To assess the effects of vaccines on influenza in healthy adults. To assess the effectiveness of vaccines in preventing cases of influenza in healthy adults. To estimate the frequency of adverse effects associated with influenza vaccination in healthy adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2004) which contains the Cochrane Acute Respiratory Infections Group trials register; MEDLINE (January 1966 to December 2003); and EMBASE (1990 to December 2003). We wrote to vaccine manufacturers and first or corresponding authors of studies in the review. Any randomised or quasi-randomised studies comparing influenza vaccines in humans with placebo, control vaccines or no intervention, or comparing types, doses or schedules of influenza vaccine. Live, attenuated or killed vaccines or fractions thereof administered by any route, irrespective of antigenic configuration were considered. Only studies assessing protection from exposure to naturally occurring influenza in healthy individuals aged 14 to 60 (irrespective of influenza immune status) were considered. Two reviewers independently assessed trial quality and extracted data. Twenty five reports of studies involving 59,566 people were included. The recommended live aerosol vaccines reduced the number of cases of serologically confirmed influenza by 48% (95% confidence interval (CI) 24% to 64%), whilst recommended inactivated parenteral vaccines had a vaccine efficacy of 70% (95% CI 56% to 80%). The yearly recommended vaccines had low effectiveness against clinical influenza cases: 15%(95% CI 8% to 21%) and 25% (95% CI 13% to 35%) respectively. Overall the percentage of participants experiencing clinical influenza decreased by 6%. Use of the vaccine significantly reduced time off work but only by 0.16 days for each influenza episode (95% CI 0.04 to 0.29 days); Analysis of vaccines matching the circulating strain gave higher estimates of efficacy, whilst inclusion of all other vaccines reduced the efficacy. Influenza vaccines are effective in reducing serologically confirmed cases of influenza. However, they are not as effective in reducing cases of clinical influenza and number of working days lost. Universal immunisation of healthy adults is not supported by the results of this review.

Vaccines for preventing influenza in people with asthma.

Influenza vaccination is recommended for asthmatic patients in many countries as observational studies have shown that influenza infection can be associated with asthma exacerbations, but influenza vaccination itself has the potential to adversely affect pulmonary function. A recent overview concluded that there was no clear benefit of influenza vaccination in patients with asthma but this conclusion was not based on a systematic search of the literature. Whilst influenza may cause asthma exacerbations, there is controversy about the use of influenza vaccinations, since they may precipitate an asthma attack in some people. The objective of this review was to assess the efficacy of influenza vaccination in children and adults with asthma. We searched the Cochrane Airways Group trials register and checked reference lists of articles. The last search was carried out in February 2003. Randomised trials of influenza vaccination in children (over two years of age) and adults with asthma. Studies involving people with chronic obstructive pulmonary disease were excluded. Inclusion criteria and assessment of trial quality were applied by two reviewers independently. Data extraction was done by two reviewers independently. Study authors were contacted for missing information. Nine trials were initially included. Four of these trials were of high quality. Five further articles have been included in two updates (Bueving 2002; Castro 2001; Redding 2002; Reid 1998). The included studies covered a wide diversity of people, settings and types of influenza vaccination, but data from the more recent studies that used similar vaccines have been pooled. The pooled results of two trials involving 2306 people with asthma did not demonstrate a significant increase in asthma exacerbations in the two weeks following influenza vaccination (Risk Difference 0.00; 95% confidence interval -0.02 to 0.02). A recent study on 696 children with asthma did not demonstrate a significant reduction in influenza related asthma exacerbations (Risk Difference 0.01; 95% confidence interval -0.02 to 0.04). Evidence from recently published trials indicates that there is no significant increase in asthma exacerbations immediately after vaccination (at least with inactivated influenza vaccination); however, uncertainty remains about the degree of protection vaccination affords against asthma exacerbations that are related to influenza infection.

Whole virus influenza vaccine activates dendritic cells (DC) and stimulates cytokine production by peripheral blood mononuclear cells (PBMC) while subunit vaccines support T cell proliferation.

Three types of trivalent influenza vaccines were analysed for their in vitro stimulatory properties on immune cells from young healthy volunteers. A whole inactivated virus (WV) vaccine, a conventional subunit (c-SU) preparation and a new virosomal subunit (v-SU) vaccine were used. Blood-derived DC up-regulated MHC class II, CD54, CD80 and CD86 after exposure to WV vaccine, indicating their functional maturation, but were only moderately affected by subunit (SU) vaccines. In addition, IL-12 and tumour necrosis factor-alpha (TNF-alpha) secretion by DC were markedly enhanced by WV, but not by SU vaccines. The production of IL-2 and interferon-gamma (IFN-gamma) by PBMC was also strongly stimulated by WV, but much less by SU vaccines, among which the v-SU vaccine was a better stimulator of IL-2 secretion. In contrast to WV vaccine both SU vaccines were powerful stimulators of PBMC proliferation. Our results suggest that the presence of influenza core components leads to the activation of DC and triggers the production of cytokines by PBMC. SU vaccines are in contrast excellent stimulators of T cell growth. A combination of WV and SU vaccines in immunization regimes might allow optimal T cell priming as well as the efficient generation and maintenance of memory cells.

A randomized, double blind study in young healthy adults comparing cell mediated and humoral immune responses induced by influenza ISCOM™ vaccines and conventional vaccines

Although current influenza vaccines have been shown to reduce influenza-related morbidity and mortality, there is a desire to develop more efficacious products. Vaccines which can induce CD8 + cytotoxic T cell (CTL) responses in addition to strong antibody responses may be more effective in preventing disease since it has been demonstrated that CTL contribute to protective immunity, even against drift variants of influenza A viruses. The immunogenicity of two types of experimental influenza vaccines, which were based on immune stimulating complexes (ISCOM™), were evaluated and compared with a conventional non-adjuvanted inactivated split virion vaccine, after immunization of human volunteers. In this randomized, double blind study, it was shown that the ISCOM™ vaccines altered the kinetics of the serum antibody response, resulting in more rapid titer rises against the vaccine strains. This accelerated antibody response coincided with enhanced in vitro proliferative T cell responses, which were observed shortly after vaccination. In addition, CTL responses were observed in a higher proportion of the vaccinees receiving an ISCOM™ vaccine, than in vaccinees receiving the conventional influenza vaccine.

Vaccines for preventing influenza in people with asthma (Cochrane Review).

Influenza vaccination is recommended for asthmatic patients in many countries as observational studies have shown that influenza infection can be associated with asthma exacerbations, but influenza vaccination itself has the potential to adversely affect pulmonary function. A recent overview concluded that there was no clear benefit of influenza vaccination in patients with asthma but this conclusions was not based on a systematic search of the literature. Whilst influenza may cause asthma exacerbations, there is controversy about the use of influenza vaccinations, since they may precipitate an asthma attack in some people. The objective of this review was to assess the effects of influenza vaccination in children and adults with asthma. We searched the Cochrane Airways Group trials register and checked reference lists of articles. Randomised trials of influenza vaccination in children (over two years of age) and adults with asthma. Studies involving people with chronic obstructive pulmonary disease were excluded. Inclusion criteria and assessment of trial quality were applied by two reviewers independently. Data extraction was done by two reviewers independently. Study authors were contacted for missing information. Nine trials were included. Four of these trials were of high quality. One further article has been included since the previous version of this review. Inclusion of the new trial has not altered the conclusions of this review. The included studies covered a wide diversity of people, settings and types of influenza vaccination, so data from the different trials were not pooled. In one trial, no protective effect of influenza vaccination against asthma exacerbation was demonstrated, but the incidence of influenza was low during the study period. A higher number of asthma exacerbations following killed influenza vaccination was found in one trial (risk difference 3 1%, 95% confidence interval 0.3% to 5.8%). When people with upper respiratory tract infections were excluded, this difference was no longer significant. A small trial using recombinant vaccine found no significant difference in asthma exacerbations between the vaccinated and placebo groups. Updated search conducted July, 2000. No new trials were identified. There is not enough evidence to assess the benefits and risks of influenza vaccination for people with asthma.

Vaccines for preventing influenza in people with cystic fibrosis.

Viral respiratory tract infections in patients with cystic fibrosis have a deteriorating effect on their lung function and disease progression. Annual influenza vaccination is therefore commonly recommended for patients with cystic fibrosis. To assess the effectiveness of influenza vaccination for patients with cystic fibrosis. We have used the Cochrane Cystic Fibrosis and Genetic Disorders Group specialist trials register which comprises references identified from comprehensive electronic database searches, hand searching relevant journals and abstract books of conference proceedings and communication to the drug companies marketing influenza vaccines. All randomised and pseudorandomised trials (published or unpublished) comparing any influenza vaccine with a placebo or with another type of influenza vaccine. Both reviewers independently assessed trial quality and extracted data. Additional information were obtained by contacting the investigators when it was indicated. Three trials enrolling a total of 115 patients with cystic fibrosis (76 (66%) were children aged one to 13 years) were included in this review. There was no study comparing a vaccine to a placebo or a whole virus vaccine to a sub unit or split virus vaccine. Two studies compared an intranasal applied live vaccine to an intramuscular inactivated vaccine and one study compared a split virus to a sub unit vaccine (both intramuscular). The incidence of all reported adverse events was high depending on the type of influenza vaccine. The total adverse event rate ranged from 48/201 (24%) for the intranasal live vaccine to 13/30 (43%) for the split virus vaccine. With the limitation of a statistical low power there was no significant difference between the study vaccinations. None of the events were severe. All study influenza vaccinations generated a satisfactory serological antibody response. No trial reported other clinically important benefits. There is currently no evidence from randomised studies that influenza vaccine given to patients with cystic fibrosis is of benefit to them. There is a need for a well constructed clinical study, that assesses the effectiveness of influenza vaccination on important clinical outcome measures.

Comparison of Serology and Reactogenicity between Influenza Subunit Vaccines and Whole Virus or Split Vaccines

Currently three different inactivated influenza vaccine types are available: whole virus (WV), split (SPL) and subunit (SU) vaccines. Physicians and patients at risk for influenza complications may wonder whether there are important differences between the vaccine types with respect to antibody induction (serology) and adverse effects (reactogenicity). A literature review (1975 to 1995) was performed to evaluate the serology and reactogenicity of SU vaccines in comparison with either split or whole virus vaccines. 22 publications with randomised allocation were identified describing a total of 5416 serological observations, 2858 observations of local reactions, and 2990 observations of systemic reactions. Subjects included those from all age groups from children to the elderly. Absolute protection and reaction rate differences (RD) were calculated for the comparisons SU vs SPL or SU vs WV vaccine. These were subjected to a method of meta-analysis, resulting in pooled rate differences and their 95% confidence intervals. With the exception of the comparison SU vs WV vaccine in subjects born after 1957 and unexposed to the reappearing H1N1 subtype after 1977, no evidence was found to suggest relevant differences in seroresponse among the three currently available inactivated influenza vaccine types. Although insufficient data were available in the meta-analysis for vaccines in children for whom specific recommendations concerning these vaccines exist, adverse events after administration of any of the three vaccine types were generally mild and transitory; however, SU vaccines were associated with a lower frequency of local and systemic reactions.

Influenza vaccines.

This is a report about influenza vaccines. Recommendations for the 1995/1996 influenza season vaccine components are cited. There are many different types of influenza vaccine, but only inactivated vaccines are licensed for parenteral administration in humans. Experimental live vaccines have been developed and evaluated for their usefulness in the immunoprophylaxis of influenza in humans, especially for those at high risk of death from influenza virus infection. The current inactivated vaccines do not provide complete protection.

Zur lokalen und systemischen Immunantwort nach Influenza- Schutzimpfung mit drei verschiedenen Vakzinetypen

Three types of inactivated bivalent influenza vaccines containing the A/Victoria/3/75 (A-Component) and B/Hongkong/8/73 (B-Component) antigens either as aluminium salt adsorbed whole virus (AlorbatTM, "A") and split virus (Begrivac STM, "B") or as fluid subunit (SandovacTM, "S") products were given to immunological homogeneous study groups of adults and children. The immune response was compared between the groups on the basis of systemic and local neuraminidase inhibiting (NI) antibody induction 4 weeks after vaccination. In evaluation of the serologic results the sea and nasal washings were tested in the ESSEN-NIT with use of the A/Eq(eq1)-VIC (N 2) recombinant antigen and the B/Hong kong/8/73 strain. The number of individuals (adults plus children) evaluated ranged from 33 to 35 per vaccine. The percentages of persons greater than or equal to 16 years old showing a significant (1.5 x, or greater) response to the A-component were 100%, 96% and 90%, respectively for the vaccine "A", "S" and "B"; the values for the B-component were 70%, 79% and 74%, respectively. The observed conversion rates in children ranged 70% to 100%. Local antibody formation was less pronounced, the percentages of significant conversions were scattered over a wide range from 13% to 80% yielding slightly better responses in children than adults. Taken altogether, the results of the trial indicate that the 3 vaccines studied induced appreciable concentrations of systemic antibodies to the neuraminidase antigen without significant differences between the vaccine types. This potency of the influenza vaccines to induce high titers of NI antibodies thus provides another marker for their immunogenicity and conceivably for their efficacy.

Isolated Hypoglossal Nerve Paralysis Following Influenza Vaccination

Isolated right hypoglossal (12th) nerve paralysis occurred after bivalent killed influenza vaccine (types A and B) immunization of a 7-month-old girl with cystic fibrosis. Two days after the third immunizing dose, fever and right hypoglossal paralysis developed. There were no other neurologic signs, and she recovered completely over the following three months.