Inactivated Influenza Research Articles

Attenuated Immune Responses to the Annual Influenza A Vaccine in Patients with Myeloproliferative Neoplasms

Background The inflammatory process plays a pivotal role in the pathogenesis of Myeloproliferative neoplasms (MPN)and immune dysregulation has been well described in this population, who may display both impaired regulatory T cell and CD4/natural killer cell function (Barosi, 2014).This inherent immune incompetence means that infections such as Influenza A (H1N1) may cause significant morbidity, even mortality, for these patients and, in general, the seasonal influenza A vaccination is recommended in immunocompromised MPN patients. To date, knowledge concerning the protective efficacy of the vaccine in this cohort is limited (Ljungman, 2005; Rieger, 2018). The aim of this study was to determine whether patients with MPN mount an adequate protective immunological response to the Influenza A vaccine (2016) when compared with healthy controls. Mass cytometric analysis using a panel of 35 antibodies was employed to assess the immune response generated following Influenza A vaccination by interrogating both innate and adaptive immune cells. Methods and Results MPN patients were invited to receive the seasonal Influenza A vaccination as recommended by the WHO in October 2016. Vaccination was administered subcutaneously with inactivated influenza A vaccine (split viron) and peripheral blood samples were collected at both 3- weeks and 3- months post vaccination. A total of 19 patients and 2 HDs were enrolled. The median age of the MPN cohort was 50 years (range 30-78). As regards disease type, 8 patients had Essential Thrombocythaemia, 7 patients Polycythaemia vera and 4 patients Myelofibrosis, of this cohort, 5 were treatment naïve, 6 patients were treated with interferon, 4 with hydroxycarbamide and 4 with a JAK inhibitor. Deep immunophenotyping was performed using a focussed high-dimensional single-cell analysis with Mass Cytometry (CyTOF). Peripheral blood mononuclear cells (PBMCs) were isolated from MPN patients 3 weeks post- (n=16), and matched 3 months' post-vaccine (n=17); and HDs 3 weeks post- (n=2), and 3 months' post-vaccination (n=2). PBMCs were stained with 35 metal-tagged antibodies and analysed using CyTOF. Automated dimension reduction method including viSNE to identify cell populations in combination with FlowSOM clustering were used. The identified cell clusters and the marker expression of each cluster of cells are summarised in figure 1. In MPN patients, an increase in abundances were identified at 3 months' post-vaccination, in a cluster of central memory (CM) CD4 T cells (p= 0.02); and Innate lymphoid cells (ILCs) (p= 8.98 x 10-4). However, the majority of defined immune cell clusters showed no significant differences in either abundances or marker expression post-vaccination (Figure 1). In contrast, for the HDs, several immune cell clusters were expanded in response to vaccination, including NK cells,CM CD4 T cells,naïve CD8 T cells, and naïve CD4 T cells. In addition, the expression of defining markers were decreased in naïve and CM CD4+T cells (p= 9.16 x 10-3), ILCs (p= 0.02); and naïve and transitional B cells (p= 0.03) between these time points. Conclusions Cell mediated immunity plays a central role in defence against the influenza infection. Vaccine mediated protection is dependent upon innate and adaptive subsystems with both T helper and cytotoxic T cell responses demonstrated in healthy individuals (Guthrie, 2004).Our data suggests that while influenza vaccination can elicit some immune response in MPN, it is not as comprehensive as that generated in HDs and the overall resultant change in immune profile of MPN patients is minimal, both in abundances and change in expression of markers across immune cell clusters and throughout both time points measured. We would also expect to observe a switch from increased proliferation of naïve cell populations to a memory phenotype, providing evidence for an adequate memory type immune response to the vaccine, but this was not the case for the analysed MPN patients. It appears that although the immune systems of MPN patients were able to recognise the Influenza A vaccine, the response was not as comprehensive as the HDs. Given the relatively low numbers of patients we have tested it is not possible to identify a single treatment or disease subtype effect and indeed these findings may not relate to either factor. Further work is required to establish if this phenomenon is treatment related or driven by the underling immune dysregulation. Disclosures Dillon: Novartis: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; TEVA: Consultancy, Honoraria. Radia:Blueprint Medicines: Consultancy; Novartis: Consultancy, Speakers Bureau. De Lavallade:BMS: Honoraria, Research Funding, Speakers Bureau; Incyte biosciences: Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Harrison:Incyte: Speakers Bureau; AOP: Honoraria; Gilead: Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; Sierra Oncology: Honoraria; Promedior: Honoraria; Roche: Honoraria; Janssen: Speakers Bureau; Celgene: Honoraria, Speakers Bureau; CTI: Speakers Bureau; Shire: Speakers Bureau. Kordasti:Celgene: Research Funding; Novartis: Research Funding; Boston Biomed: Consultancy; API: Consultancy. McLornan:Jazz Pharmaceuticals: Honoraria, Speakers Bureau; Novartis: Honoraria.

Self-reported diabetes and herpes zoster are associated with a weak humoral response to the seasonal influenza A H1N1 vaccine antigen among the elderly

BackgroundThe immune response to seasonal influenza vaccines decreases with advancing age. Therefore, an adjuvanted inactivated trivalent influenza vaccine (Fluad®) exists for elderly individuals. Fluad® is more immunogenic and efficacious than conventional influenza vaccines. However, the immune response varies and may still result in high frequencies of poor responders. Therefore, we aimed to a) examine the prevalence of a weak response to Fluad® and b) identify potential risk factors.MethodsA prospective population-based study among individuals 65–80 years old was conducted in 2015/2016 in Hannover, Germany (n = 200). Hemagglutination-inhibition titers 21 days after vaccination with Fluad® served as indicator of vaccine responsiveness.ResultsThe percentage of vaccinees with an inadequate vaccine response varied depending on the influenza strain: it was lowest for H3N2 (13.5%; 95% CI, 9.4–18.9%), intermediate for B strain (37.0%; 30.6–43.9%), and highest for H1N1 (49.0%; 42.2–55.9%). The risk of a weak response to the influenza A H1N1 strain was independently associated with self-reported diabetes (AOR, 4.64; 95% CI, 1.16–18.54), a history of herpes zoster (2.27; 1.01–5.10) and, to a much lesser extent, increasing age (change per year, 1.08; 0.99–1.16). In addition, herpes zoster was the only risk factor for a weak response to the H3N2 antigen (AOR, 3.12; 1.18–8.23). We found no significant association between sex, Body Mass Index, cancer, hypertension, heart attack and CMV seropositivity and a weak response to these two influenza A antigens. Despite its occurence in over one third of vaccinees, none of the variables examined proved to be risk factors for a weak response to the B antigen.ConclusionsA considerable proportion of elderly individuals displayed a weak vaccine response to this adjuvanted seasonal influenza vaccine and further efforts are thus needed to improve immune responses to influenza vaccination among the elderly. Diabetes and herpes zoster were identified as potentially modifiable risk factors for a poor vaccine response against influenza A antigens, but the results also reveal the need for broader investigations to identify risk factors for inadequate responses to influenza B antigens.Trial registrationNo. NCT02362919 (ClinicalTrials.gov, date of registration: 09.02.2015).

Protection afforded by avian influenza vaccination programmes consisting of a novel RNA particle and an inactivated avian influenza vaccine against a highly pathogenic avian influenza virus challenge in layer chickens up to 18 weeks post-vaccination

ABSTRACTThe efficacies of an oil adjuvanted-inactivated reverse genetics-derived H5 avian influenza virus (AIV) vaccine and an alphavirus replicon RNA particle (RP) AIV vaccine were evaluated in commercial Leghorn chickens. Challenge utilized A/turkey/MN/12582/2015, an isolate representing the U.S. H5N2 Clade 2.3.4.4 responsible for the 2015 highly pathogenic avian influenza (HPAI) epornitic in commercial poultry the United States. As part of a long-term, 36-week study, chickens were challenged at seven weeks of age after receiving a single vaccination, at 18 weeks of age following a vaccine prime-single boost, and at 36 weeks of age after a prime- double-boost. All vaccine programmes reduced virus oropharyngeal and cloacal shedding and mortality compared to the non-vaccinated control birds; however, chickens receiving at least one administration of the RP vaccine generally had diminished viral shedding especially from the cloacal swabbings. A detectable serum antibody response and protection were observed through 18 weeks post-vaccination. Our data suggest that, in conjunction with a comprehensive eradication, enhanced biosecurity and controlled marketing plan, vaccination programmes of commercial layer chickens with novel RP vaccines may represent an important tool for preventing HPAI-related mortalities and decreasing viral load during a catastrophic influenza outbreak.RESEARCH HIGHLIGHTSImmunization of poultry following a vaccination schedule consisting of inactivated and RNA particle vaccines offered significant protection against lethal disease following HPAIV challenge.Virus shedding was significantly (P < 0.05) reduced in chickens vaccinated with either inactivated and/or recombinant vaccines.Serum antibody titres were not a reliable indicator of protection.An inactivated vaccine containing 384 HAU of the homologous antigen was unable to induce complete protection.

Safety, Tolerability and Immunogenicity of an Trivalent Inactivated Cell-Culture Influenza Vaccine in Healthy Adults

Safety, Tolerability and Immunogenicity of an Trivalent Inactivated Cell-Culture Influenza Vaccine in Healthy Adults

Generation of H7N9-specific human polyclonal antibodies from a transchromosomic goat (caprine) system

To address the unmet needs for human polyclonal antibodies both as therapeutics and diagnostic reagents, building upon our previously established transchromosomic (Tc) cattle platform, we report herein the development of a Tc goat system expressing human polyclonal antibodies in their sera. In the Tc goat system, a human artificial chromosome (HAC) comprising the entire human immunoglobulin (Ig) gene repertoire in the germline configuration was introduced into the genetic makeup of the domestic goat. We achieved this by transferring the HAC into goat fetal fibroblast cells followed by somatic cell nuclear transfer for Tc goat production. Gene and protein expression analyses in the peripheral blood mononuclear cells (PBMC) and the sera, respectively, of Tc caprine demonstrated the successful expression of human Ig genes and antibodies. Furthermore, immunization of Tc caprine with inactivated influenza A (H7N9) viruses followed by H7N9 Hemagglutinin 1 (HA1) boosting elicited human antibodies with high neutralizing activities against H7N9 viruses in vitro. As a small ungulate, Tc caprine offers the advantages of low cost and quick establishment of herds, therefore complementing the Tc cattle platform in responses to a range of medical needs and diagnostic applications where small volumes of human antibody products are needed.

Primary Ovarian Insufficiency and Adolescent Vaccination.

Published case series have suggested a potential association between human papillomavirus (HPV) vaccination and primary ovarian insufficiency (POI). We describe POI incidence and estimate POI risk after HPV; tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis, adsorbed (Tdap); inactivated influenza (II); and meningococcal conjugate (MenACWY) vaccination. We searched Kaiser Permanente Northwest electronic health records for outpatient diagnoses suggestive of POI in female patients aged 11 to 34 years between 2006 and 2014. We reviewed and adjudicated the medical record to confirm diagnoses and estimate symptom onset dates. We excluded cases with known causes and calculated the incidence of idiopathic POI. We estimated risk by calculating hazard ratios and 95% confidence intervals (CIs). From a cohort of 199 078 female patients, we identified 120 with diagnoses suggestive of POI. After adjudication and exclusion of 26 POI cases with known causes, we confirmed 46 idiopathic POI cases. POI incidence was low in 11- to 14-year-olds (0.87 per 1 000 000 person-months) and increased with age. One confirmed case patient received the HPV vaccine 23 months before the first clinical evaluation for delayed menarche. The adjusted hazard ratio was 0.30 (95% CI: 0.07-1.36) after HPV, 0.88 (95% CI: 0.37-2.10) after Tdap, 1.42 (95% CI: 0.59-3.41) after II, and 0.94 (95% CI: 0.27-3.23) after MenACWY vaccination. We did not find a statistically significant elevated risk of POI after HPV, Tdap, II, or MenACWY vaccination in this population-based retrospective cohort study. These findings should lessen concern about POI risk after adolescent vaccination.

Systemic and mucosal humoral immune responses induced by the JY-adjuvanted nasal spray H7N9 vaccine in mice

Since the first case of human avian influenza A (H7N9) virus infection in 2013, five H7N9 epidemics have occurred in China, all of which caused severe diseases, including pneumonia and acute respiratory distress syndrome, and the fatality rates of these epidemics were as high as 30–40%. To control the prevalence of H7N9 influenza, an effective vaccine is urgently needed. In the present study, we used chitosan and recombinant human interleukin-2 as an adjuvant (JY) to promote the systemic and mucosal immune responses induced by the H7N9 vaccine. Mice were immunized intranasally with the inactivated split influenza A (H7N9) virus (A/Shanghai/02/2013) vaccine with or without JY. The hemagglutination inhibition (HI) titers of mice immunized with the JY-adjuvanted vaccine were significantly higher than those of mice immunized with the vaccine without adjuvant (21.11 ± 9.58 vs. 5.04 ± 3, P < 0.05). The JY-adjuvanted H7N9 nasal spray vaccine induced higher HI titers (8 ± 0.82 vs. 6.7 ± 0.67, P = 0.0035) than those did the poly (I:C)-adjuvanted H7N9 vaccine or the LTB-adjuvanted H7N9 vaccine (8 ± 0.82 vs. 6.9 ± 0.88, P = 0.0186). The optimal immunization regimen for the nasal spray H7N9 vaccine was determined to be a 21-day interval between the primary immunization and booster, with a dose of 4.5 μg hemagglutinin per mouse. The immunogenicities of the nasal spray H7N9 vaccine and intramuscular vaccine (containing only the inactivated split virus) were compared in mice. Two doses of the nasal spray H7N9 vaccine induced higher titers of HI (6.7 ± 0.67 vs. 5.3 ± 1.16, P = 0.004) and anti-HA IgG in sera (19.26 ± 0.67 vs. 13.97 ± 0.82, P < 0.0001) and of anti-HA sIgA (7.13 ± 2.54 vs. 0, P = 0.0000) in bronchoalveolar lavage fluid (BALF) than one dose of intramuscular H7N9 vaccine 3 weeks after the last immunization. However, when we immunized the mice with two doses of both vaccines separately, the nasal spray H7N9 vaccine induced higher titers of anti-HA IgG (19.26 ± 0.67 vs. 17.56 ± 0.57, P < 0.0001) and anti-HA sIgA (7.13 ± 2.54 vs. 4.02 ± 0.33, P = 0.0026) than did the intramuscular H7N9 vaccine, and there was no difference in HI titer between the two groups (P = 0.3745). This finding indicates that the JY-adjuvanted nasal spray H7N9 vaccine induced not only the systemic immune response but also a local mucosal response, which may improve the efficacy of H7N9 influenza prevention through respiratory tract transmission.

Virus-derived immunostimulatory RNA induces type I IFN-dependent antibodies and T-cell responses during vaccination

Adjuvants potentiate and direct the type of immunity elicited during vaccination. However, there is a shortage of adjuvants that elicit robust type-1 immunity required for the control of intracellular pathogens, including viruses. RNA derived from Sendai virus defective viral genomes (DVGs) stimulates RIG-I-like receptor signaling leading to type-1 immunity during infection. Here, we investigated whether a 268nt DVG-derived oligonucleotide (DDO) functions as a strong type-1 immunity-inducing adjuvant during vaccination against influenza virus. We show that DDO induces robust IgG2c antibody production when used in an inactivated influenza A virus (IAV) vaccine. Additionally, DDO induces Th1 and CD8+ T-cell responses able to protect against heterosubtypic IAV challenge. Interestingly, DDO synergized with AddaVax and skewed the immune response towards type-1 immunity. The adjuvancy of DDO alone and in synergy with AddaVax was heavily dependent on type I interferon signaling. Our data support a critical role for type I interferon in the induction of type-1 immune responses during vaccination and demonstrate that DDO is a type-1 immunity orienting vaccine adjuvant that can be used alone or in synergy with other adjuvants.

Assessment of an optimized manufacturing process for inactivated quadrivalent influenza vaccine: a phase III, randomized, double-blind, safety and immunogenicity study in children and adults

BackgroundGSK has modified the licensed monovalent bulk manufacturing process for its split-virion inactivated quadrivalent influenza vaccine (IIV4) to harmonize the process among different strains, resulting in an increased number of finished vaccine doses, while compensating for the change from inactivated trivalent influenza vaccine (IIV3) to IIV4. To confirm the manufacturing changes do not alter the profile of the vaccine, a clinical trial was conducted to compare IIV4 made by the currently licensed process with a vaccine made by the new (investigational) process (IIV4-I). The main objectives were to compare the reactogenicity and safety of IIV4-I versus IIV4 in all age groups, and to demonstrate the non-inferiority of the hemagglutination-inhibition (HI) antibody responses based on the geometric mean titer ratio of IIV4-I versus IIV4 in children.MethodsThe Phase III, randomized, double-blind, multinational study included three cohorts: adults (18–49 years; N = 120), children (3–17 years; N = 821), and infants (6–35 months; N = 940). Eligible subjects in each cohort were randomized 1:1 to receive IIV4-I or IIV4. Both vaccines contained 15 μg of hemagglutinin antigen for each of the four seasonal virus strains. Adults and vaccine-primed children received one dose of vaccine, and vaccine-unprimed children received two doses of vaccine 28 days apart. All children aged ≥9 years were considered to be vaccine-primed and received one dose of vaccine.ResultsThe primary immunogenicity objective of the study was met in demonstrating immunogenic non-inferiority of IIV4-I versus IIV4 in children. The IIV4-I was immunogenic against all four vaccine strains in each age cohort. The reactogenicity and safety profile of IIV4-I was similar to IIV4 in each age cohort, and there was no increase in the relative risk of fever (≥38 °C) with IIV4-I versus IIV4 within the 7-day post-vaccination period in infants (1.06; 95% Confidence Interval: 0.75, 1.50; p = 0.786).ConclusionsThe study demonstrated that in adults, children, and infants, the IIV4-I made using an investigational manufacturing process was immunogenic with a reactogenicity and safety profile that was similar to licensed IIV4. These results support that the investigational process used to manufacture IIV4-I is suitable to replace the current licensed process.Trial registrationClinicalTrials.gov: NCT02207413; trial registration date: August 4, 2014.

Protective efficacy of an inactivated bivalent swine influenza vaccine

Protective efficacy of an inactivated bivalent swine influenza vaccine

Studies on the effect of different immunostimulants on chick's immune response to inactivated avian influenza and Newcastle Vaccines

Studies on the effect of different immunostimulants on chick's immune response to inactivated avian influenza and Newcastle Vaccines

Effects of recombinant Agrocybe aegerita lectin as an immunoadjuvant on immune responses

Context: Accumulated evidence has indicated that recombinant Agrocybe aegerita lectin (AAL) possesses immunoadjuvant activity to enhance antigen-specific immune responses. However, the mechanism of how AAL regulates immune response remains poorly defined.Aim: This study is aimed to reveal the mechanism of AAL’s immunoadjuvant activity.Methods: In this study, AAL alone or combined with inactivated avian influenza virus H9N2 was immunized to mice and the transcriptome profile of immunized mice was analyzed.Results: In line with previous studies, our results showed that H9N2-specific IgG level was significantly increased in AAL-treated mice, suggesting the immunoadjuvant activity of AAL. More importantly, transcriptome data revealed that genes participating in the primary adherence, lymphocyte activation, secondary adherence and transmembrane migration of leukocyte migration, were up-regulated by AAL.Conclusion: These findings suggest that AAL exerts immunoadjuvant effects by promoting chemotaxis and phagotrophy activity of neutrophil leucocyte and macrophage to improve innate immunity and antigen presentation.

Safety and effectiveness assessment of 2011–2012 seasonal influenza vaccine produced in China: a randomized trial

ABSTRACTObjective: This study evaluated the effectiveness and safety of the egg-based, trivalent, inactivated split influenza vaccine produced by the Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, China.Methods: From March 2012 through May 2012, we enrolled a total of 1390 healthy volunteers between the ages of 3 and 80 years in a randomized clinical trial at the Hebei Disease Control Center Vaccine Clinical Evaluation Center. For all subjects, body part adverse reactions and whole-body adverse reactions were observed 30 min, 6 h, and 1–7 days’ post-inoculation. If no severe adverse effects were observed 7 days’ post-vaccination, the local and systemic reactions of preliminary test participants were recorded until day 28. There was no placebo group in this study. Blood samples were taken for serological testing before vaccination and 28 days’ post-vaccination.Results: Twenty-eight days after vaccination, the seroconversion rates of experimental and control groups were H1N1 75.3% and 75.7%, H3N2 75.8% and 71.8%, B 70.7% vs. 69.4%, (P > 0.05). The antibody Geometric Mean Titer（GMT）of experimental and control groups were H1N1 (179.7, 182.4), H3N2 (584.0, 445.7), B (201.4,191.6). The protection rate of experimental and control groups was not statistically significant (H1N1: 86% vs. 87%, H3N2: 99% vs. 98%, B: 98% vs. 98%). Also, 95% confidence intervals of the protection rate difference between the experimental and the control group were H1N1: −0.1% (−4.1,3.8) %, H3N2: 0.3% (−1.0,1.7) % and B: 0.2% (−1.5,1.9) %; confidence intervals exceeded the limit of −5%. The rates of adverse reactions between experimental and control groups were 6.3% and 7.7% in local response reactions, and 19.5% and 18.0% in systemic reactions. Three hundred and twenty-seven adverse events (AEs) in 1200 (27.76%) subjects were reported within 28 d after vaccination. No serious adverse events occurred during the study.Conclusions: The experimental vaccine three-antibody protection rate was non-inferior to the control vaccine. Our results demonstrated that the experimental vaccine achieved the primary immunogenic end point of the intended clinical protocol, as well as a secondary immunogenic end-point, with an acceptable level of safety. IRB approval for this study was issued under #2012Y0005 and registered as Clinical Trial No. NCT01551810.

An inactivated influenza D virus vaccine partially protects cattle from respiratory disease caused by homologous challenge

Originally isolated from swine, the proposed influenza D virus has since been shown to be common in cattle. Inoculation of IDV to naïve calves resulted in mild respiratory disease histologically characterized by tracheitis. As several studies have associated the presence of IDV with acute bovine respiratory disease (BRD), we sought to investigate the efficacy of an inactivated IDV vaccine. Vaccinated calves seroconverted with hemagglutination inhibition titers 137–169 following two doses. Non-vaccinated calves challenged with a homologous virus exhibited signs of mild respiratory disease from days four to ten post challenge which was significantly different than negative controls at days five and nine post challenge. Peak viral shedding of approximately 5 TCID50/mL was measured in nasal and tracheal swabs and bronchoalveolar lavage fluids four to six days post challenge. Viral titers were significantly (P<0.05) decreased 1.4 TCID50/mL, 3.6 TCID50/mL and 5.0 TCID50/mL, respectively, in the aforementioned samples collected from vaccinated animals compared to non-vaccinated controls at peak shedding. Viral antigen was detected in the respiratory epithelium of the nasal turbinates and trachea by immunohistochemistry from all unvaccinated calves but in significantly fewer vaccinates. Inflammation characterized by neutrophils was observed in the nasal turbinate and trachea but not appreciably in lungs. Together these results support an etiologic role for IDV in BRD and demonstrate that partial protection is afforded by an inactivated vaccine.

Protective neutralizing influenza antibody response in the absence of T follicular helper cells.

Virus infection induces the development of T follicular helper (TFH) and T helper 1 (TH1) cells. Although TFH cells are important in anti-viral humoral immunity, the contribution of TH1 cells to a protective antibody response remains unknown. We found that IgG2 antibodies predominated in the response to vaccination with inactivated influenza A virus (IAV) and were responsible for protective immunity to lethal challenge with pathogenic H5N1 and pandemic H1N1 IAV strains, even in mice that lacked TFH cells and germinal centers. The cytokines interleukin-21 and interferon-γ, which are secreted from TH1 cells, were essential for the observed greater persistence and higher titers of IgG2 protective antibodies. Our results suggest that TH1 induction could be a promising strategy for producing effective neutralizing antibodies against emerging influenza viruses.

Comparative immunological study between inactivated Avian Influenza H5N1 virus vaccines adjuvated with montanide oil ISA70 and ISA71

Comparative immunological study between inactivated Avian Influenza H5N1 virus vaccines adjuvated with montanide oil ISA70 and ISA71

Safety, immunogenicity and cross-reactivity of a Northern hemisphere 2013–2014 seasonal trivalent inactivated split influenza virus vaccine, Anflu®

ABSTRACTAnflu® is a seasonal trivalent inactivated split-virion influenza vaccine manufactured by Sinovac Biotech Co., Ltd. The objectives of this study were to evaluate the safety of Anflu® (2013–14 formulation: H1N1, H3N2 and BYAM) in infants and adults and its immunogenicity and cross-reactivity against mismatched influenza B lineage and avian influenza A(H7N9) viruses (hereafter BVIC and H7N9, respectively) in adults. In this phase IV open label trial, infants 6–35 months old (n=61) each received two injections with 28 days apart; adults 18–60 yrs old (n=60) and elderly >60 yrs old (n=61) each received one injection. Information of adverse events was collected through safety observation and follow-up visits. Pre- and post-immune blood samples (day 0 and 21) were collected from subjects ≥18 yrs old to detect hemagglutination inhibition antibody titers and calculate seroprotection rates (SPRs) and seroconversion rates (SCRs). The overall adverse reaction incidence was 1.6% (3/182), and no serious adverse event was reported during the study period. For subjects ≥18 yrs old, the SCRs, SPRs, and the geometric mean titers (GMTs) met the European criteria for all three strains. In addition, the point estimations of SCR, SPR and GMT for BVIC also met the European criteria. Six subjects were seroconverted against H7N9; however the serological results did not meet the European criteria. In conclusion, the results showed a satisfactory safety and immunogenicity profile of Anflu® and cross-reactivity against BVIC, but did not demonstrate cross-reactivity against H7N9 (Clinicaltrials.gov ID: NCT02269852).

Клиническая и иммунологическая безопасность инактивированной иммуноадъювантной субъединичной вакцины против гриппа для беременных

Клиническая и иммунологическая безопасность инактивированной иммуноадъювантной субъединичной вакцины против гриппа для беременных

Post-marketing surveillance of adverse events following immunization with inactivated quadrivalent and trivalent influenza vaccine in health care providers in Western Australia

In 2015, inactivated quadrivalent influenza vaccine (QIV) was first introduced into the Australian market. A routine vaccine safety surveillance system in Western Australia was used to conduct post-licensure surveillance of adverse events following immunization with inactivated QIV and trivalent influenza vaccines (TIV) in a sample of 1685 healthcare providers (HCPs). A similar percentage of HCPs who received QIV reported having any reaction seven days post-vaccination as HCPs who received TIV (13.6 vs. 12.8%, respectively; p=0.66). However, a slightly higher percentage of HCPs who received QIV reported pain or swelling at the injection site as compared to HCPs who received TIV (6.9% vs. 4.2%, respectively; p=0.02). No serious vaccine-associated adverse events were detected during follow-up of either vaccine. Acknowledging the study limitations, the results of this post-marketing surveillance support the safety of QIV, suggesting there is little difference in the reactogenicity of QIV as compared to TIV.

Positive regulation of humoral and innate immune responses induced by inactivated Avian Influenza Virus vaccine in broiler chickens.

Avian Influenza (AI) vaccines are widely used for mammals and birds in a trial to eliminate the Avian Influenza virus (AIV) infection from the world. However and up till now the virus is still existed via modulation of its antigenic structure to evade the pressure of host immune responses. For a complete understanding of the immune responses following AI vaccination in chickens, the modulations of the chickens humoral immune responses and interferon-alpha signaling pathway, as a fundamental part of the innate immune responses, were investigated. In our study, we measured the humoral immune response using hemagglutination-inhibition (HI) and enzyme-linked immunosorbent assay (ELISA) tests. In addition, chicken interferon-alpha pathway components was measured at RNA levels using Quantitative Real-time PCR (qRT-PCR) following one dose of inactivated H5N1 influenza vaccine at 14 days of age. In this study, the protective levels of humoral antibody responses were observed at 14, 21 and 28 days following immunization with inactivated (Re-1/H5N1) AI vaccine. In the chicken spleen cells, up regulation in the chicken interferon-alpha pathway components (MX1 & IRF7) was existed as early as 48 h post vaccination and remained until 28 days post vaccination at the endogenous state. However, after the recall with ex-vivo stimulation, the up regulation was more pronounced in the transcriptional factor (IRF7) compared to the antiviral gene (MX1) at 28 days post vaccination. So far, from our results it appears that the inactivated H5N1 vaccine can trigger the chicken interferon-alpha signaling pathway as well as it can elicit protective humoral antibody responses.