Hemagglutinin stem reactive antibody response in individuals immunized with a seasonal influenza trivalent vaccine.
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ABSTRACT:
SUBMITTER: Zhao X
PROVIDER: S-EPMC4444808 | biostudies-literature | 2015 Jun
REPOSITORIES: biostudies-literature
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Hemagglutinin stem reactive antibody response in individuals immunized with a seasonal influenza trivalent vaccine.
Zhao Xiaopeng X Qin Kun K Guo Jinlei J Wang Donghong D Li Zi Z Zhu Wenfei W Liu Liqi L Wang Dayan D Shu Yuelong Y Zhou Jianfang J
Protein & cell 20150601 6
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Project description:Annual influenza vaccination reduces the risks of influenza when the vaccines are well matched to circulating strains, but development of an approach that induces broader and more durable immune responses would be beneficial. We conducted two companion Phase 1 studies, VRC 307 and VRC 309, over sequential seasons (2008-2009 and 2009-2010) in which only the influenza B strain component of the vaccines differed. Objectives were safety and immunogenicity of prime-boost vaccination schedules. A schedule of DNA vaccine encoding for seasonal influenza hemagglutinins (HA) prime followed by seasonal trivalent influenza inactivated vaccine (IIV3) boost (HA DNA-IIV3) was compared to placebo (PBS)-IIV3 or IIV3-IIV3. Cumulatively, 111 adults were randomized to HA DNA-IIV3 (n=66), PBS-IIV3 (n=25) or IIV3-IIV3 (n=20). Safety was assessed by clinical observations, laboratory parameters and 7-day solicited reactogenicity. The seasonal HA DNA prime-IIV3 boost regimen was evaluated as safe and well tolerated. There were no serious adverse events. The local and systemic reactogenicity for HA DNA, IIV and placebo were reported predominantly as none or mild within the first 5days post-vaccination. There was no significant difference in immunogenicity detected between the treatment groups as evaluated by hemagglutination inhibition (HAI) assay. The studies demonstrated the safety and immunogenicity of seasonal HA DNA-IIV3 regimen, but the 3-4week prime-boost interval was suboptimal for improving influenza-specific immune responses. This is consistent with observations in avian H5 DNA vaccine prime-boost studies in which a long interval, but not a short interval, was associated with improved immunogenicity.Trial registrationNCT00858611 for VRC 307 and NCT00995982 for VRC 309.
| S-EPMC4751067 | biostudies-literature
Project description:The target of neutralizing antibodies that protect against influenza virus infection is the viral protein HA. Genetic and antigenic variation in HA has been used to classify influenza viruses into subtypes (H1-H16). The neutralizing antibody response to influenza virus is thought to be specific for a few antigenically related isolates within a given subtype. However, while heterosubtypic antibodies capable of neutralizing multiple influenza virus subtypes have been recently isolated from phage display libraries, it is not known whether such antibodies are produced in the course of an immune response to influenza virus infection or vaccine. Here we report that, following vaccination with seasonal influenza vaccine containing H1 and H3 influenza virus subtypes, some individuals produce antibodies that cross-react with H5 HA. By immortalizing IgG-expressing B cells from 4 individuals, we isolated 20 heterosubtypic mAbs that bound and neutralized viruses belonging to several HA subtypes (H1, H2, H5, H6, and H9), including the pandemic A/California/07/09 H1N1 isolate. The mAbs used different VH genes and carried a high frequency of somatic mutations. With the exception of a mAb that bound to the HA globular head, all heterosubtypic mAbs bound to acid-sensitive epitopes in the HA stem region. Four mAbs were evaluated in vivo and protected mice from challenge with influenza viruses representative of different subtypes. These findings reveal that seasonal influenza vaccination can induce polyclonal heterosubtypic neutralizing antibodies that cross-react with the swine-origin pandemic H1N1 influenza virus and with the highly pathogenic H5N1 virus.
| S-EPMC2860935 | biostudies-literature
Project description:The assurance of vaccine potency is important for the timely release and distribution of influenza vaccines. As an alternative to Single Radial Immunodiffusion (SRID), we report a new quantitative enzyme-linked immunosorbent assay (ELISA) for seasonal trivalent influenza vaccine (TIV). The consensus hemagglutinin (cHA) stalks for group 1 influenza A virus (IAV), group 2 IAV, and influenza B virus (IBV) were designed and produced in bacterial recombinant host in a soluble form, and monoclonal antibodies (mAbs) were generated. The group-specific 'universal' mAbs (uAbs) bound to various subtypes of HAs in the same group from recombinant hosts, embryonated eggs, and commercial vaccine lots. The calibration curves were generated to assess the sensitivity, specificity, accuracy, and linear dynamic range. The quantitative ELISA was validated for the potency assay of individual components of TIV- H1, H3, and IBV- with good correlation with the SRID method. This new assay could be extended to pandemic or pre-pandemic mock-up vaccines of H5 of group 1 and H7 virus of group 2, and novel HA stalk-based universal vaccines.
| S-EPMC6927952 | biostudies-literature
Project description:Conventional inactivated avian influenza vaccines have performed poorly in past vaccine trials, leading to the hypothesis that they are less immunogenic than seasonal influenza vaccines. We tested this hypothesis by comparing the immunogenicity of the H5N1 and H7N9 vaccines (avian influenza vaccines) to a seasonal trivalent inactivated influenza vaccine in naïve ferrets, administered with or without the adjuvants MF59 or AS03. Vaccine immunogenicity was assessed by measuring neutralizing antibody titers against hemagglutinin and neuraminidase and by hemagglutinin -specific IgG levels. Two doses of unadjuvanted vaccines induced low or no HA-specific IgG responses and hemagglutination-inhibiting titers. Adjuvanted vaccines induced comparable IgG-titers, but poorer neutralizing antibody titers for the H5 vaccine. All adjuvanted vaccines elicited detectable anti- neuraminidase -antibodies with the exception of the H5N1 vaccine, likely due to the low amounts of neuraminidase in the vaccine. Overall, the H5N1 vaccine had poorer capacity to induce neutralizing antibodies, but not HA-specific IgG, compared to H7N9 or trivalent inactivated influenza vaccine.
| S-EPMC5627238 | biostudies-literature
Project description:Seasonal influenza vaccine formulations must be updated annually to correspond to the influenza viruses in circulation. This was an uncontrolled, open-label, multi-center phase IV study conducted in Belgium to comply with interim European Medicines Agency (EMA) guidelines for rapidly evaluating the safety of newly formulated seasonal influenza vaccines. Adult volunteers received one dose of the 2014-2015 Northern Hemisphere formulation of licensed intradermal trivalent influenza vaccine at either the standard dose (9µg hemagglutinin/strain for 18-59 year-olds) or the high dose (15µg hemagglutinin/strain for ≥ 60 year-olds). Vaccinees recorded their solicited reactions and unsolicited adverse events for 7 d after vaccination. Solicited reaction frequencies were compared to historical reference values obtained from previous clinical trials to determine if the new formulations were excessively reactogenic or allergenic. A total of 210 participants (105 per age group) were included and vaccinated in October 2014. In both groups, pain, erythema, and pruritus were the most common solicited injection site reactions, and headache and myalgia were the most common solicited systemic reactions. Although the frequencies of shivering in 18-59 year-olds and malaise in ≥ 60 year-olds were higher than historical reference values, they were not considered indicative of excessive reactogenicity because almost all of these reactions were mild. The study design was endorsed by the EMA and permitted the reactogenicity of both vaccine formulations to be assessed within one month by collecting adverse events for 7 d. Both formulations exhibited acceptable safety profiles although this should be confirmed through forthcoming enhanced post-marketing safety surveillance systems.
| S-EPMC5404648 | biostudies-literature
Project description:BackgroundThe conserved, immuno-subdominant influenza virus hemagglutinin (HA) stalk region is a potential universal group-specific influenza virus vaccine epitope. We analyzed antibody responses to H1 hemagglutinin stalk domain (H1/stalk) following trivalent influenza inactivated vaccine (IIV3) immunization in pregnant women, and association with protection against influenza virus illness.MethodsOne hundred forty-five human immunodeficiency virus (HIV)-uninfected pregnant women (68 IIV3 and 77 placebo recipients) and 140 pregnant women with HIV infection (72 IIV3 and 68 placebo recipients) were independently randomized in placebo-controlled efficacy trials of IIV3. Plasma samples were tested for H1/stalk immunoglobulin G (IgG) and hemagglutination inhibition (HAI) antibodies prevaccination and 1 month postvaccination. Women had weekly surveillance for influenza illness, confirmed by polymerase chain reaction.ResultsIncreases in H1/stalk IgG (and HAI) antibody levels were elicited post-IIV3, with responses being higher in HIV-uninfected women than in women living with HIV. Among HIV-uninfected vaccinees, there was no correlation (postvaccination) between H1/stalk and HAI antibody responses, whereas a strong correlation was observed in vaccinees with HIV. The H1/stalk IgG concentration was lower among women developing A/H1N1 illness (85.3 arbitrary units [AU]/mL) than those without A/H1N1 illness (219.6 AU/mL; P = .001). H1/stalk IgG concentration ≥215 AU/mL was associated with 90% lower odds (odds ratio, 0.09; P = .005) of A/H1N1 illness. Also, H1/stalk IgG was significantly lower among women with influenza B illness (93.9 AU/mL) than among their counterparts (215.5 AU/mL) (P = .04); however, no association was observed after adjusting for HAI titers.ConclusionsH1/stalk IgG concentration was associated with lower odds for A/H1N1 influenza virus illness, indicating its potential as an epitope for a universal vaccine against group 1 influenza virus.
| S-EPMC7428398 | biostudies-literature
Project description:Despite the availability of seasonal vaccines and antiviral medications, influenza virus continues to be a major health concern and pandemic threat due to the continually changing antigenic regions of the major surface glycoprotein, hemagglutinin (HA). One emerging strategy for the development of more efficacious seasonal and universal influenza vaccines is structure-guided design of nanoparticles that display conserved regions of HA, such as the stem. Using the H1 HA subtype to establish proof of concept, we found that tandem copies of an alpha-helical fragment from the conserved stem region (helix-A) can be displayed on the protruding spikes structures of a capsid scaffold. The stem region of HA on these designed chimeric nanoparticles is immunogenic and the nanoparticles are biochemically robust in that heat exposure did not destroy the particles and immunogenicity was retained. Furthermore, mice vaccinated with H1-nanoparticles were protected from lethal challenge with H1N1 influenza virus. By using a nanoparticle library approach with this helix-A nanoparticle design, we show that this vaccine nanoparticle construct design could be applicable to different influenza HA subtypes. Importantly, antibodies elicited by H1, H5, and H7 nanoparticles demonstrated homosubtypic and heterosubtypic cross-reactivity binding to different HA subtypes. Also, helix-A nanoparticle immunizations were used to isolate mouse monoclonal antibodies that demonstrated heterosubtypic cross-reactivity and provided protection to mice from viral challenge via passive-transfer. This tandem helix-A nanoparticle construct represents a novel design to display several hundred copies of non-trimeric conserved HA stem epitopes on vaccine nanoparticles. This design concept provides a new approach to universal influenza vaccine development strategies and opens opportunities for the development of nanoparticles with broad coverage over many antigenically diverse influenza HA subtypes.
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Project description:Influenza virus infections are responsible for significant morbidity worldwide and therefore it remains a high priority to develop more broadly protective vaccines. Adjuvation of current seasonal influenza vaccines has the potential to achieve this goal.To assess the immune potentiating properties of Matrix-M™, mice were immunized with virosomal trivalent seasonal vaccine adjuvated with Matrix-M™. Serum samples were isolated to determine the hemagglutination inhibiting (HAI) antibody titers against vaccine homologous and heterologous strains. Furthermore, we assess whether adjuvation with Matrix-M™ broadens the protective efficacy of the virosomal trivalent seasonal vaccine against vaccine homologous and heterologous influenza viruses.Matrix-M™ adjuvation enhanced HAI antibody titers and protection against vaccine homologous strains. Interestingly, Matrix-M™ adjuvation also resulted in HAI antibody titers against heterologous influenza B strains, but not against the tested influenza A strains. Even though the protection against heterologous influenza A was induced by the adjuvated vaccine, in the absence of HAI titers the protection was accompanied by severe clinical scores and body weight loss. In contrast, in the presence of heterologous HAI titers full protection against the heterologous influenza B strain without any disease symptoms was obtained.The results of this study emphasize the promising potential of a Matrix-M™-adjuvated seasonal trivalent virosomal influenza vaccine. Adjuvation of trivalent virosomal vaccine does not only enhance homologous protection, but in addition induces protection against heterologous strains and thus provides overall more potent and broad protective immunity.
| S-EPMC4672496 | biostudies-literature
Project description:Objective: Current evidence on the immunogenicity of influenza vaccination in patients with chronic obstructive pulmonary disease (COPD) is limited. To address this need for additional knowledge, we conducted a study on the immunogenicity of trivalent seasonal influenza vaccine (TIV) in COPD patients.Methods: We recruited patients from respiratory outpatient clinics of three hospitals in Tangshan, Hebei province who had stable confirmed COPD, were less than 80 y old, and reported not having had influenza or receiving TIV during the study season prior to enrollment. Patients who had a history of allergy to any TIV component or were classified as having very severe COPD were excluded from the study. Eligible and consenting participants were given one dose of TIV after obtaining a baseline blood sample. A second blood sample was obtained 5 weeks later. We used hemagglutination inhibition (HI) assays to measure antibody responses. We considered seropositive to be an HI titer ≥1:10. We considered seroprotection to be an HI titer ≥1:40 and seroconversion to be either a change from seronegative to a post-vaccination titer of ≥1:40 or a fourfold rise in antibody titer among baseline seropositive subjects. Each subject was followed for 1 month to assess the frequency and type of adverse events.Results: Eighty-eight subjects completed our study; the median age was 64 y; most (62.5%) had moderately severe COPD; 48.9% of the subjects had comorbid conditions in addition to COPD. Post-vaccination seropositive rates for influenza H1N1, H3N2, and B were all 100%; corresponding seroprotection rates were 96.6%, 93.2%, and 98.9%; seroconversion rates were 81.8%, 87.5%, and 75.0%. There were no statistical differences in seroconversion (P = .10) and seroprotection (P = .30) among the three types of influenza virus. Geometric mean titers (1:) of HI antibodies to H1N1, H3N2, and B were 18.8 (95% CI: 14.0-25.1), 12.2 (95% CI: 9.6-15.4), and 31.8 (95% CI: 26.1-38.8) at baseline, and 267.0 (95% CI: 213.8-333.4), 190.3 (95% CI: 151.7-238.6), and 201.1 (95% CI: 166.5-242.8) after vaccination.Conclusion: The immunogenicity of one dose of influenza vaccine was excellent in COPD patients. Our study supports recommending influenza vaccination for COPD patients to provide protection from influenza and its complications.
| S-EPMC8381819 | biostudies-literature
Project description:Vaccination has been a successful strategy in influenza prevention. However, despite the safety and efficacy of the vaccines, they can cause adverse events following immunization (AEFI). Moreover, due to the vaccination success, most of vaccine-preventable diseases (VPD) have become rare, and public attention has been shifted from VPD to the AEFI associated with vaccination. This manuscript describes the safety of Instituto Butantan (IB) seasonal trivalent influenza vaccine (TIV) from 2013 to 2017. AEFI data were received by the Department of Pharmacovigilance of IB (PV-IB), from January the 1st 2013 to December the 31st 2017, and were recorded in an electronic database (OpenClinica©). PV-IB received 1,415 Individual Case Safety Reports (ICSR) associated with the TIV; 1,253 ICSR with at least one AEFI were analyzed and 4,140 AEFI were identified. The other 162 (11.4%) cases did not present any symptom. Among the total of AEFI, 405 (9.8%) were classified as serious. AEFI with the highest incidence rates per 100,000 doses of TIV were: "local pain" (0.28), "local erythema" (0.23), "local warmth" (0.22), "local swelling" (0.20) and "fever" (0.19). PV-IB received 175 (4.2%) occurrences of SAE of special interest, of which 75 (1.8%) anaphylaxis/anaphylactic reactions, 56 (1.4%) neurological syndromes (including seven Guillain-Barré Syndrome) and 44 (1.1%) convulsion/febrile convulsion. The results of this manuscript suggested that Instituto Butantan trivalent influenza vaccine (IB-TIV) is safe, as most of the reported AEFI were classified as non-serious. AEFI described for the IB-TIV are in agreement with the ones described in the literature for similar vaccines.
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