Trivalent Split-virus Influenza Vaccine Research Articles

Safety and Immunogenicity of Enterovirus 71 Vaccine (Vero Cell) Administered Simultaneously with Trivalent Split-Virion Influenza Vaccine in Infants Aged 6-7 Months: A Phase 4, Randomized, Controlled Trial.

Objective: To assess the immunogenicity and safety of the enterovirus 71 vaccine (Vero cell) (EV71 vaccine) and trivalent split-virion influenza vaccine (IIV3). Methods: Healthy infants aged 6-7 months were recruited from Zhejiang Province, Henan Province, and Guizhou Province and randomly assigned to the simultaneous vaccination group, EV71 group, and IIV3 group at a ratio of 1:1:1. Then, 3 mL blood samples were collected before vaccination and 28 days after the second dose of vaccine. Cytopathic effect inhibition assay was used to detect EV71 neutralization antibody, and cytopathic effect inhibition assay was used to detect influenza virus antibody. Results: A total of 378 infants were enrolled and received the first dose of vaccine and were included in the safety analysis, and 350 infants were involved in the immunogenicity analysis. The adverse events rates were 31.75%, 28.57%, and 34.13% in the simultaneous vaccination group, EV71 group, and IIV3 group (p > 0.05), respectively. No vaccine-related serious adverse events were reported. After two doses of EV71 vaccine, the seroconversion rates of EV71 neutralizing antibody were 98.26% and 97.37% in the simultaneous vaccination group and the EV71 group, respectively. After two doses of IIV3, the simultaneous vaccination group and the IIV3 group, respectively, had seroconversion rates of 80.00% and 86.78% for H1N1 antibody, 99.13% and 98.35% for H3N2 antibody, and 76.52% and 80.99% for B antibody. There was no statistically significant difference in the seroconversion rates of influenza virus antibodies between groups (p > 0.05). Conclusions: The coadministration of EV71 vaccine and IIV3 has good safety and immunogenicity in infants aged 6-7 months.

SAFETY AND EFFECTIVENESS OF TRI VALENT INACTIVATED SPLIT VIRION INFLUENZA VACCINE IN PATIENTS WITH RHEUMATOID DISORD ERS

Objective: to evaluate the safety and effectiveness of vaccination with trivalent split virion influenza vaccine in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS), estimate the effect of vaccination on rheumatoid disorder (RD) activity and influenza and influenzalike illnesses morbidity.Materials and methods. The study included 86 patients (58 females and 28 males aged 22–82 years) with RDs (52 patients with RA and 34 patients with AS), as well as 40 subjects without RD (control group). At the time of study inclusion, all patients were receiving drug therapy. Duration of RD varied from 2 months to 46 years. The Vaxigrip vaccine containing the currents trains of the flu virus for 2016–2017 season or 2017–2018 season was administered subcutaneously as 1 dose (0.5 ml) with continuing antirheumatic therapy. The main control stages were visits 1, 3, and 6 months after vaccination. During the visits, standard clinical and labtests, clinical examination with disease activity evaluation were performed.Results. In 98 patients, vaccination tolerability was high, no post vaccination reactions were observed. In 20 cases, pain, swelling, and hyperemia of the skin 2 cm in diameter at the point of vaccination were observed; in 8 cases, low-grade fever, myalgia, discomfort, headache were observed. No RD flares or development of new autoimmune disorders were diagnosed during the follow-up period. No cases of influenza or influenza-like illnesses were registered during the follow-up period.Conclusion. The obtained data demonstrate high tolerability, clinical effectiveness of trivalent split virion influenza vaccine in patients with RA and AS.

Quadrivalent inactivated influenza vaccine (VaxigripTetra™)

ABSTRACTIntroduction: VaxigripTetra™ (IIV4; Sanofi Pasteur) is a quadrivalent split-virion influenza vaccine approved in Europe in 2016 for individuals ≥ 3 years of age. IIV4 builds on the well-established record of the trivalent split-virion influenza vaccine (Vaxigrip®).Areas covered: This literature review summarizes the rationale for developing quadrivalent influenza vaccines and discusses the phase III clinical trial results supporting the immunogenicity, safety, and tolerability of IIV4.Expert commentary: IIV4 is immunogenic and well tolerated. Adding a second B strain to the trivalent split-virion influenza vaccine provides a superior immune response for the additional strain but does not reduce the immune response for the three other strains or negatively affect the safety profile. By offering broader protection against co-circulating influenza B lineages, IIV4 has the potential to further reduce influenza-related morbidity and mortality beyond that achieved with trivalent vaccines.

Safety and immunogenicity of a quadrivalent intradermal influenza vaccine in adults

BackgroundAn intradermal (ID) trivalent split-virion influenza vaccine (IIV3-ID) (Fluzone® Intradermal, Sanofi Pasteur, Swiftwater, PA) has been available in the US since the 2011/2012 influenza season for adults aged 18–64 years. This study examined whether adding a second B-lineage strain affects immunogenicity and safety. MethodsThis randomized, double-blind, multicentre trial evaluated the immunogenicity and safety of an intradermal quadrivalent split-virion influenza vaccine (IIV4-ID) in adults 18–64 years of age in the US during the 2012–2013 influenza season. Participants were randomized 2:1:1 to receive a single injection of IIV4-ID, licensed IIV3-ID, or an investigational IIV3-ID containing the alternate B-lineage strain. Haemagglutination inhibition antibody titres were assessed in two-thirds of participants before vaccination and 28 days after vaccination. Results1672 participants were vaccinated with IIV4-ID, 837 with licensed IIV3-ID, and 846 with an investigational IIV3-ID. For all four vaccine strains, antibody responses to IIV4-ID were statistically non-inferior to the response to the IIV3-ID vaccines containing the matched strains. For both B strains, post-vaccination antibody responses to IIV4-ID were statistically superior to the responses to IIV3-ID lacking the corresponding B strain. Adverse events were similar for IIV4-ID and IIV3-ID. The most commonly reported solicited reactions were pain, pruritus, myalgia, headache, and malaise; and most were grade 1 or 2 and appeared and resolved within 3 days of vaccination. IIV4-ID was statistically non-inferior to the two pooled IIV3-ID vaccines for the proportions of participants with at least one grade 2 or 3 systemic reaction. ConclusionsAntibody responses to the IIV4-ID were non-inferior to IIV3-ID for the A and matched B strains and superior for the unmatched B strains. IIV4-ID was well tolerated without any safety concerns. IIV4-ID may help address an unmet need due to mismatched B strains in previous influenza vaccines.

Zanamivir versus trivalent split virus influenza vaccine: a pilot randomized trial.

BackgroundHealthcare workers may be exposed to people with respiratory viral infections more often than other working adults. Understanding the risk and the effectiveness of different preventive measures is of great importance.ObjectivesTo estimate adherence to prophylactic antiviral medication for a full influenza season, to the compare efficacy of antiviral prophylaxis to that of the seasonal influenza vaccine and to identify exposures that increase risk of acute respiratory illnesses (ARI) in healthy adults.MethodsParticipants were randomized 1:2 to receive the 2008–2009 influenza vaccine or daily prophylaxis with 10 mg of zanamivir during the season. Web-based questionnaires collected information on demographics, symptoms, exposures, medication use and side effects.ResultsSixty-four healthy adults were recruited in November 2008. Three of 40 active participants discontinued zanamivir due to side effects; the remaining 37 took >85% of scheduled doses for a median of 121 days. Symptomatic, laboratory-confirmed influenza was detected in one person randomized to zanamivir (2·5%) and 2/20 (10%) who received the vaccine (P = 0·25). Forty-seven participants reported 109 episodes of ARI. Factors associated with an ARI were exposure to a spouse (OR 7·2), child (OR 2·4) or patient (OR 2·0) with symptoms of an ARI in the previous 7 days.ConclusionsBreakthrough influenza infection occurred in both vaccinated participants and those receiving antiviral prophylaxis. Most adults were willing and able to comply with season-long prophylaxis. Report of recent exposure to family members and patients with an ARI increased the risk of developing an ARI in healthy adults.

Influenza symptoms and their impact on elderly adults: randomised trial of AS03‐adjuvanted or non‐adjuvanted inactivated trivalent seasonal influenza vaccines

BackgroundPatient-reported outcomes (PROs) are particularly relevant in influenza vaccine trials in the elderly where reduction in symptom severity could prevent illness-related functional impairment.ObjectivesTo evaluate PROs in people aged ≥65 years receiving two different vaccines.MethodsThis was a phase III, randomised, observer-blind study (NCT00753272) of the AS03-adjuvanted inactivated trivalent split-virion influenza vaccine (AS03-TIV) versus non-adjuvanted vaccine (TIV). Using the FluiiQ questionnaire, symptom (systemic, respiratory, total) and life impact (activities, emotions, relationships) scores were computed as exploratory endpoints, with minimal important difference (MID) in influenza severity between vaccines considered post-hoc as >7%. Vaccine efficacy of AS03-TIV relative to TIV in severe influenza (hospitalisation, complication, most severe one-third of episodes based on the area under the curve for systemic symptom score) was calculated post-hoc. The main analyses (descriptive) were conducted in the according-to-protocol cohort (n = 280 AS03-TIV, n = 315 TIV) for influenza confirmed by culture or reverse transcriptase polymerase chain reaction.ResultsMean systemic symptom, total symptom and impact on activities scores were lower with AS03-TIV versus TIV. Mean respiratory symptom, impact on emotions and impact on relationships scores were similar. Influenza tended to be less severe with AS03-TIV, but the MID was reached only for impact on activities (mean 9·0%). Relative vaccine efficacy in severe influenza was 29·38% (95% CI: 7·60–46·02).ConclusionsAS03-TIV had advantages over TIV in impact on systemic symptoms and activities as measured by the FluiiQ in elderly people. Higher efficacy of AS03-TIV relative to TIV was shown for prevention of severe illness.

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. However, influenza vaccination has the potential to cause wheezing and adversely affect pulmonary function. While an overview concluded that there was no clear benefit of influenza vaccination in patients with asthma, this conclusion was not based on a systematic search of the literature. The objective of this review was to assess the efficacy and safety of influenza vaccination in children and adults with asthma. We searched the Cochrane Airways Group trials register and reviewed reference lists of articles. The latest search was carried out in November 2012. We included randomised trials of influenza vaccination in children (over two years of age) and adults with asthma. We excluded studies involving people with chronic obstructive pulmonary disease. Inclusion criteria and assessment of trial quality were applied by two review authors independently. Data extraction was done by two review authors independently. Study authors were contacted for missing information. Nine trials were included in the first published version of this review, and nine further trials have been included in four updates. The included studies cover a wide diversity of people, settings and types of influenza vaccination, and we pooled data from the studies that employed similar vaccines. PROTECTIVE EFFECTS OF INACTIVATED INFLUENZA VACCINE DURING THE INFLUENZA SEASON: A single parallel-group trial, involving 696 children, was able to assess the protective effects of influenza vaccination. There was no significant reduction in the number, duration or severity of influenza-related asthma exacerbations. There was no difference in the forced expiratory volume in one second (FEV) although children who had been vaccinated had better symptom scores during influenza-positive weeks. Two parallel-group trials in adults did not contribute data to these outcomes due to very low levels of confirmed influenza infection. ADVERSE EFFECTS OF INACTIVATED INFLUENZA VACCINE IN THE FIRST TWO WEEKS FOLLOWING VACCINATION: Two cross-over trials involving 1526 adults and 712 children (over three years old) with asthma compared inactivated trivalent split-virus influenza vaccine with a placebo injection. These trials excluded any clinically important increase in asthma exacerbations in the two weeks following influenza vaccination (risk difference 0.014; 95% confidence interval -0.010 to 0.037). However, there was significant heterogeneity between the findings of two trials involving 1104 adults in terms of asthma exacerbations in the first three days after vaccination with split-virus or surface-antigen inactivated vaccines. There was no significant difference in measures of healthcare utilisation, days off school/symptom-free days, mean lung function or medication usage.EFFECTS OF LIVE ATTENUATED (INTRANASAL) INFLUENZA VACCINATION: There were no significant differences found in exacerbations or measures of lung function following live attenuated cold recombinant vaccine versus placebo in two small studies on 17 adults and 48 children. There were no significant differences in asthma exacerbations found for the comparison live attenuated vaccine (intranasal) versus trivalent inactivated vaccine (intramuscular) in one study on 2229 children (over six years of age). Uncertainty remains about the degree of protection that vaccination affords against asthma exacerbations that are related to influenza infection. Evidence from more recently published randomised trials of inactivated split-virus influenza vaccination indicates that there is no significant increase in asthma exacerbations immediately after vaccination in adults or children over three years of age. We were unable to address concerns regarding possible increased wheezing and hospital admissions in infants given live intranasal vaccination.

Post-marketing Surveillance Study of an Inactivated Split-Virion Influenza Vaccine in Korea

Purpose : This post-marketing surveillance study (NCT00750360) assessed the safety and reactogenicity of an inactivated, trivalent split-virion influenza vaccine licensed for use in the Korea since 2002. Methods : Eight hundred and eighty three subjects aged 6 months received a single dose of the vaccine; an additional dose was administered to those aged 6 years: 34.7%), fever (6 years: 13.9%) were the most frequently recorded solicited local and general adverse events. Grade 3 solicited adverse events were reported by 4.0% subjects. No vaccine-related SAEs were recorded (KFDA criteria). Conclusion : Considering the vaccine's well-established immunogenicity and its favourable safety and reactogenicity profile across all age groups and its high coverage rate in Korea, it may be recommended as a candidate to facilitate annual seasonal influenza vaccination for all ages as part of the Korean National Immunization Program.

Immunogenicity, large scale safety and lot consistency of an intradermal influenza vaccine in adults aged 18–60 years: Randomized, controlled, Phase III trial

Background: Vaccination is the most effective way of reducing the large health and economic burden of influenza, yet vaccination coverage remains low, particularly among non-elderly adults. Intradermal influenza vaccine produce an effective immune response and represents an alternative to intramuscular influenza vaccination. Methods: A Phase III multicentre, randomised, controlled, double-blind (for the three different lots of intradermal vaccine) study assessed lot-to-lot consistency, immunogenicity and safety of an intradermal inactivated trivalent split-virion influenza vaccine in 2255 adults aged 18–60 years. Participants received one of three lots of intradermal vaccine containing 9 µg of haemagglutinin per influenza strain, or a licensed intramuscular control vaccine containing 15 µg haemagglutinin/strain. Results: The three industrial lots of intradermal vaccine were equivalent in terms of post-vaccination titres elicited by day 21. The intradermal and intramuscular vaccines induced similar post-vaccination titres, and satisfied all three immunogenicity criteria set out in the European regulatory guidelines for influenza vaccines for each of the three influenza strains. The solicited systemic reaction profile and the incidence and type of spontaneously reported adverse events were similar in the two vaccine groups and in line with the known safety profile of inactivated influenza vaccines. Injection site reactions were more frequent with intradermal vaccination. Conclusions: This intradermal vaccine containing 9 µg per influenza strain, provides an alternative to conventional intramuscular vaccination, has a reliable production method and is equally immunogenic and well tolerated in adults. The study was registered at clinicaltrials.gov (identifier NCT00383539).

The safety and immunogenicity of influenza vaccine in children with asthma in Mexico

The morbidity and mortality associated with influenza is substantial in children with asthma. There are no available data on the safety and immunogenicity of influenza vaccine in children with asthma in Latin America. Furthermore, it is unclear if influenza vaccination may cause asthma exacerbations. We conducted a placebo-controlled trial to investigate the safety and immunogenicity of an inactivated trivalent split virus influenza vaccine in children with asthma in Mexico. We also measured the impact of influenza vaccination on pulmonary function tests in this population. The inactivated influenza vaccine was immunogenic and safe in terms of local and systemic side effects compared to placebo. We observed no significant impact on pulmonary function tests among vaccine recipients. Given the significant morbidity associated with influenza in children, strategies to promote increased influenza vaccination coverage in this high-risk group in Latin America and elsewhere are urgently needed.

Influenza immunisation in children with solid tumours

We assessed response to immunisation with trivalent split virus influenza vaccine in children with non-leukaemic malignant disease. Children with solid tumours and lymphoma received one or two doses of influenza vaccine, according to current UK guidelines, in autumn 2001 and/or 2002. Children were currently receiving chemotherapy or were within 6 months of completing chemotherapy. Pre and post vaccination sera were assessed for antibodies to the prevalent influenza strains by haemagglutination inhibition (HI). Sixty six children were assessed prior to 69 episodes of vaccination. In 30% episodes, children were susceptible to all three circulating influenza viruses (65% to H1N1, 42% to H3N2 and 90% to B) and only one patient showed protective titres (HI ⩾ 32) against all three strains. Seroresponse rates (⩾4-fold rise in HI) for H1N1, H3N2 and B were 52%, 33% and 51% in 65 episodes. Following immunisation protective titres to all three viruses were seen in 25 episodes (38%) and protective responses to one or two viruses were seen in a further 12 (19%) episodes. There was no significant difference in response rates among children on treatment and off treatment and by intensity of chemotherapy. Children with solid tumours and lymphoma are highly susceptible to influenza infection. Influenza vaccine was well tolerated in this patient group and children showed a significant response to immunisation. These findings support the recommendation for annual influenza vaccination in these children.

Immune response to influenza vaccine in healthy adults and the elderly: association with nutritional status

The immune response and serum nutritional status of 153 elderly residents of nursing homes (mean age 84.4 years) and 95 health care workers (mean age 36.8 years) were assessed before and after immunization with trivalent split-virus influenza vaccine. Postvaccination titers of hemagglutination inhibition (HAI) antibody to A/H1N1 and B among the elderly were lower than those among workers, but the seroconversion rates (greater than or equal to a four-fold rise) for A/H1N1 and A/H3N2 were unexpectedly higher among the elderly than among workers. However, the difference in the seroconversion rate for either strain between workers and the elderly disappeared after adjusting for the prevaccination HAI titer. Among all subjects, lower age and higher serum concentrations of total protein, albumin, Vitamin E and folate were associated with an intact immune response (postvaccination HAI titers ≥40 for at least one strain). In an age-adjusted analysis limited to the elderly, however, only Vitamin E showed a significant association with the immune response. These results suggested that Vitamin E may play an important role in maintaining the immune response, especially among the elderly.

Immune response to influenza vaccination in children and adults with asthma: effect of corticosteroid therapy

BackgroundAnnual influenza vaccination is currently recommended as a preventative measure for all patients with asthma. However, the effect of maintenance corticosteroid therapy on the immune response to influenza vaccine has received limited evaluation. ObjectiveIn this study, we evaluated the effect of corticosteroid therapy on the immune response to influenza vaccine in children and adults with asthma. MethodsThis was a substudy of a larger multicenter, randomized, double-masked, placebo-controlled, crossover study investigating the safety of trivalent influenza vaccine in patients with asthma. At baseline, 294 subjects were randomized to receive either placebo first (n=139) or inactivated trivalent split-virus influenza vaccine first (n=155). Study subjects were categorized into 2 groups: subjects in group 1 (n=148) were receiving medium-dose or high-dose inhaled corticosteroids (ICSs) or oral corticosteroids, whereas subjects in group 2 (n=146) were not receiving corticosteroids or were receiving low-dose ICSs. Serum hemagglutination inhibition antibody titers for the vaccine antigens were measured before and 4 weeks after the administration of placebo or vaccine. ResultsSerologic responses to each influenza vaccine antigen were significantly higher in vaccine than in placebo recipients and were similar among influenza vaccine recipients in groups 1 and 2 for the following endpoints: rise in antibody titer, percent of participants who developed a serological response, and percent of subjects who developed a serum hemagglutination inhibition antibody titer ≥1:32. Post hoc subgroup analyses demonstrated an attenuated response to influenza B antigen in subjects receiving high-dose ICS compared with subjects who were steroid-naïve (P<.05). ConclusionThe immune response to the A antigens of the inactivated influenza vaccine in subjects with asthma is not adversely affected by ICS therapy. High-dose ICS therapy may diminish the response to the B antigen of the vaccine, an observation that needs further investigation.

Inactivated influenza vaccine is safe for children and adults with stable asthma

(2001) N Engl J Med 345, 1529. American Lung Association Asthma Clinical Research Centers. . The safety of inactivated influenza vaccine in adults and children with asthma. . Nov 22;...

The inactivated trivalent split-virus influenza vaccine was safe in stable asthma

Source Citation American Lung Association Asthma Clinical Research Centers. The safety of inactivated influenza vaccine in adults and children with asthma. N Engl J Med. 2001 Nov 22;345:1529-36. 11...

Response to influenza immunisation during treatment for cancer

AIMSTo assess the annual risk of influenza infection in children with cancer and the immunogenicity of a trivalent split virus influenza vaccine in these children.METHODSEighty four children with cancer were...

The hemagglutination inhibition antibody responses to an inactivated influenza vaccine among healthy adults: with special reference to the prevaccination antibody and its interaction with age

The immunogenicity of the trivalent split-virus influenza vaccine was investigated among 70 healthy adults (mean age: 48.5, range: 36–68). The vaccine antigens were: A/Yamagata/32/89 (H1N1); A/Beijing/352/89 (H3N2); and B/Bangkok/163/90. Regarding the entire sample, the vaccine induced a tenfold or more rise on the average in the hemagglutination inhibition (HAI) antibody to each antigen. The response rates (greater than or equal to a fourfold rise) were about 90% or more among those with a prevaccination titer ≤1:64 (equivalent to ≤1:16 on the Western scale: in Japan, the HAI titers are expressed by the final, and not the initial, dilution of the serum; from hereon our findings will be expressed using the Japanese scale), whereas they were 0–50% at ≥1:128. Thus, the prevaccination titer was negatively associated with antibody induction. The achievement rates (postvaccination titer ≥1:128) among those with a prevaccination titer <1:16 remained at 48–68%. Regarding the analysis of variance, a significant effect on antibody induction was indicated for the prevaccination titer ( P≤0.002), but not for age ( P≥0.425). The interaction between the prevaccination titer and age was significant for A/Yamagata ( P=0.030), while it was also suggestive for A/Beijing ( P=0.054): as age increased, those with no preexisting antibody (<1:16) showed greater titer rises, in contrast to the smaller rises among those with a titer ≥1:16. Based on the attack survey conducted separately, the vaccine efficacy on influenza-like illnesses with fever ≥37°C and ≥37.5°C was calculated to be 16% (95% confidence interval: −66% to 57%) and 37% (−55% to 74%), respectively.

Antibody response of pediatric solid organ transplant recipients to immunization against influenza virus

We studied the immunogenicity of the 1992-1993 trivalent split-virus influenza vaccine in pediatric solid organ transplant recipients (PSOTRs) and their healthy siblings. One month after immunization, 41 (82%) of 50 subjects achieved protective titers of antibodies to influenza A, and 30 (60%) to influenza B, rates similar to those in healthy siblings. Achievement and persistence of protective titers occurred significantly more often in children with preexisting antibody. We recommend annual immunization of PSOTRs, their household contacts, and health care workers; immunologically naive PSOTRs may benefit from immunization before transplantation. (J P EDIATR 1995;127:957-60)

Influenza vaccine and anticoagulation control in patients receiving warfarin

SummaryThe effects of a trivalent split virion influenza vaccine on anticoagulation control were prospectively evaluated in a sample of well‐controlled warfarin recipients. Vaccine‐induced changes in prothrombin time ratios were not detected during one month of follow‐up after immunisation. The results are supported by the findings of other studies conducted in this country and the USA, which have all refuted the conclusions of early reports that suggested a possible interaction between warfarin and influenza vaccine.