Influenza Antibody Research Articles

The Efficacy of Influenza Vaccination is Reduced in Nursing Home Older Adults With Moderate to Severe Renal Impairment

In patients with end stage renal failure, the immune response toward influenza vaccination and its efficacy to reduce mortality are inferior to patients with normal renal function. 1 Suga T. Niki H. Niikura M. et al. Influenza antibody titers after vaccination of chronic renal failure patients. Tokai J Exp Clin Med. 1990; 15: 245-251 PubMed Google Scholar , 2 Gilbertson D.T. Unruh M. McBean A.M. et al. Influenza vaccine delivery and effectiveness in end stage renal disease. Kidney Int. 2003; 63: 738-743 Crossref PubMed Scopus (99) Google Scholar In 2009, the pandemic H1N1 infection had caused significant mortality in Hong Kong, with 90% virus isolated being H1N1. 3 Wu J.T. Ma E.S.K. Lee C.K. et al. The infection attack rate and severity of 2009 pandemic H1N1 influenza in Hong Kong. Clin Infect Dis. 2010; 51: 1184-1191 Crossref PubMed Scopus (163) Google Scholar , 4 Center of Health Protection. The Government of the Hong Kong. Monthly summary tables of influenza virus isolation 2009. Available at: http://www.chp.gov.hk/. Accessed January 7, 2012. Google Scholar The dual vaccination (seasonal influenza and H1N1) strategy offered additional benefits in reducing mortality in older adults, 5 Chan T.C. Hung I.F. Luk J.K. et al. Efficacy of dual vaccination of pandemic H1N1 2009 influenza and seasonal influenza on institutionalized elderly: A one-year prospective cohort study. Vaccine. 2011; 29: 7773-7778 Crossref PubMed Scopus (16) Google Scholar and this study further examined whether this strategy is still efficacious in older adults with renal dysfunction.

Structural and genetic basis for development of broadly neutralizing influenza antibodies

Influenza viruses take a yearly toll on human life despite efforts to contain them with seasonal vaccines. These viruses evade human immunity through the evolution of variants that resist neutralization. The identification of antibodies that recognize invariant structures on the influenza haemagglutinin (HA) protein have invigorated efforts to develop universal influenza vaccines. Specifically, antibodies to the highly conserved stem region of HA neutralize diverse viral subtypes. These antibodies largely derive from a specific antibody gene, heavy-chain variable region IGHV1-69, after limited affinity maturation from their germline ancestors, but how HA stimulates naive B cells to mature and induce protective immunity is unknown. To address this question, we analysed the structural and genetic basis for their engagement and maturation into broadly neutralizing antibodies. Here we show that the germline-encoded precursors of these antibodies act as functional B-cell antigen receptors (BCRs) that initiate subsequent affinity maturation. Neither the germline precursor of a prototypic antibody, CR6261 (ref. 3), nor those of two other natural human IGHV1-69 antibodies, bound HA as soluble immunoglobulin-G (IgG). However, all three IGHV1-69 precursors engaged HA when the antibody was expressed as cell surface IgM. HA triggered BCR-associated tyrosine kinase signalling by germline transmembrane IgM. Recognition and virus neutralization was dependent solely on the heavy chain, and affinity maturation of CR6261 required only seven amino acids in the complementarity-determining region (CDR) H1 and framework region 3 (FR3) to restore full activity. These findings provide insight into the initial events that lead to the generation of broadly neutralizing antibodies to influenza, informing the rational design of vaccines to elicit such antibodies and providing a model relevant to other infectious diseases, including human immunodeficiency virus/AIDS. The data further suggest that selected immunoglobulin genes recognize specific protein structural 'patterns' that provide a substrate for further affinity maturation.

Elicitation of Broadly Neutralizing Influenza Antibodies in Animals with Previous Influenza Exposure

The immune system responds to influenza infection by producing neutralizing antibodies to the viral surface protein, hemagglutinin (HA), which regularly changes its antigenic structure. Antibodies that target the highly conserved stem region of HA neutralize diverse influenza viruses and can be elicited through vaccination in animals and humans. Efforts to develop universal influenza vaccines have focused on strategies to elicit such antibodies; however, the concern has been raised that previous influenza immunity may abrogate the induction of such broadly protective antibodies. We show here that prime-boost immunization can induce broadly neutralizing antibody responses in influenza-immune mice and ferrets that were previously infected or vaccinated. HA stem-directed antibodies were elicited in mice primed with a DNA vaccine and boosted with inactivated vaccine from H1N1 A/New Caledonia/20/1999 (1999 NC) HA regardless of preexposure. Similarly, gene-based vaccination with replication-defective adenovirus 28 (rAd28) and 5 (rAd5) vectors encoding 1999 NC HA elicited stem-directed neutralizing antibodies and conferred protection against unmatched 1934 and 2007 H1N1 virus challenge in influenza-immune ferrets. Indeed, previous exposure to certain strains could enhance immunogenicity: The strongest HA stem-directed immune response was observed in ferrets previously infected with a divergent 1934 H1N1 virus. These findings suggest that broadly neutralizing antibodies against the conserved stem region of HA can be elicited through vaccination despite previous influenza exposure, which supports the feasibility of developing stem-directed universal influenza vaccines for humans.

Highly Conserved Protective Epitopes on Influenza B Viruses

Identification of broadly neutralizing antibodies against influenza A viruses has raised hopes for the development of monoclonal antibody-based immunotherapy and "universal" vaccines for influenza. However, a substantial part of the annual flu burden is caused by two cocirculating, antigenically distinct lineages of influenza B viruses. Here, we report human monoclonal antibodies, CR8033, CR8071, and CR9114, that protect mice against lethal challenge from both lineages. Antibodies CR8033 and CR8071 recognize distinct conserved epitopes in the head region of the influenza B hemagglutinin (HA), whereas CR9114 binds a conserved epitope in the HA stem and protects against lethal challenge with influenza A and B viruses. These antibodies may inform on development of monoclonal antibody-based treatments and a universal flu vaccine for all influenza A and B viruses.

Adaptations of a Competitive Enzyme-Linked Immunosorbent Assays for the Detection of Antibodies to Influenza A Virus in Horse Sera for Use in Wild Aquatic Birds

We applied a competitive enzyme-linked immunosorbent assay for the detection of antibodies for influenza A in equine sera to their detection in sera from wild aquatic birds. Suboptimal results were obtained for the optical density (OD) of the monoclonal antibody (MAb) control and reproducibility between duplicate analyses in the initial assessment. It was therefore necessary to modify the assay to deliver increased reliability and reproducibility while maintaining adequate sensitivity. We optimized reagent concentrations to obtain optimal OD values (close to 2) for the monoclonal antibody control and used 2, 2'-Azino-bis: 3-Benzthiazoline-6-Sulphonic Acid as an alternative chromogen to potentially reduce variability in duplicate analyses. The original assay was compared with the optimized versions, with and without post coating, for the detection of avian influenza viral antibodies in 240 sera obtained from wild plumed whistling ducks. A separate analytical sensitivity study on diluted positive field sera of plumed whistling ducks and a test of antigen stability after post coating were also performed. Some quantitative differences were detected between the original and modified assays. The original assay recorded higher percentage inhibition results which were potentially indicative of increased sensitivity. However, when reagent concentrations were increased in the original assay to the same levels as used in the modified versions, there were no quantitative differences for practical purposes. The original assay produced a median (OD) value of 0.81 for the (MAb) controls that is at the limit of acceptability. By contrast, the modified assays always produced acceptable optical density values for MAb controls. Our overall results indicated the modified assays were potentially more reliable (OD values close to 2), and of adequate sensitivity compared to the original assay in the detection of avian influenza viral antibodies in wild bird sera. Although further optimization of antigen and MAb concentrations should also be considered to increase the sensitivity of a modified assay, while maintaining acceptable optical density values for the MAb control. Post coating had a minimal quantitative effect on the results and stabilized the plates for 214days. We therefore recommend the incorporation of post coating.

Comparison of serological assays for detecting antibodies in ducks exposed to H5 subtype avian influenza virus

BackgroundChicken red blood cells (RBCs) are commonly used in hemagglutination inhibition (HI) tests to measure hemagglutinating antibodies against influenza viruses. The use of horse RBCs in the HI test can reportedly increase its sensitivity when testing human sera for avian influenza antibodies. This study aims to compare the proportion of positives detected and the agreement between two HI tests using either chicken or horse red blood cells for antibody detection in sera of ducks experimentally infected or naturally exposed to Indonesian H5 subtype avian influenza virus. In addition, comparison with a virus neutralisation (VN) test was conducted with the experimental sera.ResultsIn the experimental study, the proportion of HI antibody-positive ducks increased slightly, from 0.57 when using chicken RBCs to 0.60 when using horse RBCs. The HI tests indicated almost perfect agreement (kappa = 0.86) when results were dichotomised (titre ≥ 4 log2), and substantial agreement (weighted kappa = 0.80) for log titres. Overall agreements between the two HI tests were greater than between either of the HI tests and the VN test. The use of horse RBCs also identified a higher proportion of antibody positives in field duck sera (0.08, compared to chicken RBCs 0.02), with also almost perfect agreements for dichotomized results (Prevalence and bias adjusted Kappa (PABAK) = 0.88) and for log titres (weighted PABAK = 0.93), respectively. Factors that might explain observed differences in the proportion of antibody-positive ducks and in the agreements between HI tests are discussed.ConclusionIn conclusion, we identified a good agreement between HI tests. However, when horse RBCs were used, a higher proportion of sera was positive (titre ≥ 4 log2) than using chicken RBCs, especially during the early response against H5N1 virus. The HRBC-HI might be more responsive in identifying early H5N1 HPAI serological response and could be a recommended assay for avian influenza sero-surveillance in both wild and domestic birds.

Pre-vaccination immunity and immune responses to a cell culture-derived whole-virus H1N1 vaccine are similar to a seasonal influenza vaccine

BackgroundImmune responses to novel pandemic influenza vaccines may be influenced by previous exposure to antigenically similar seasonal strains. MethodsAn open-label, randomized, phase I/II study was conducted to assess the immunogenicity and safety of a non-adjuvanted, inactivated whole-virus H1N1 A/California/07/2009 vaccine. 408 subjects were stratified by age (18–59 and >60 years) and randomized 1:1 to receive two vaccinations with either 3.75 or 7.5μg hemagglutinin antigen 21 days apart. Safety, immunogenicity and the influence of seasonal influenza vaccination and antibody cross-reactivity with a seasonal H1N1 strain was assessed. ResultsA single vaccination with either dose induced substantial increases in H1N1 A/California/07/2009 hemagglutination inhibition (HI) and neutralizing (MN) antibody titers in both adult and elderly subjects. A single 7.5μg dose induced seroprotection rates of 86.9% in adults and 75.2% in elderly subjects. Two 7.5μg vaccinations induced seroprotection rates in adult and elderly subjects of 90.9% and 89.1%, respectively. The robust immune response to vaccination was confirmed by analyses of neutralizing antibody titers. Both HI and MN antibodies persisted for ≥6 months post-vaccination. Between 34% and 49% of subjects had seroprotective levels of H1N1 A/California/07/2009 antibodies at baseline. Higher baseline HI titers were associated with receipt of the 2008–09 or 2009–10 seasonal influenza vaccine. High baseline A/California/07/2009 neutralizing antibody titers were also associated with high baseline titers against A/New Caledonia/20/99, a seasonal H1N1 strain which circulated and was included in the seasonal vaccine from 2000–01 to 2006–07. Pre-adsorption with A/H1N1/New Caledonia/20/99 antigen reduced A/H1N1/California/07/2009 baseline titers in 55% of tested sera. The vaccine was well tolerated with low rates of fever. ConclusionsA whole-virus H1N1 A/California/07/2009 vaccine was safe and well tolerated and a single dose induced substantial immune responses similar to seasonal influenza vaccines, probably due to immunological priming by previous seasonal influenza vaccines or infections.

Prevalence and incidence of Newcastle disease and prevalence of Avian Influenza infection of scavenging village chickens in Timor-Lesté

A longitudinal study to monitor prevalence and incidence of antibodies against Newcastle disease (ND) virus and prevalence of antibodies against Avian Influenza (AI) virus in scavenging village chickens was conducted in 20 villages within 4 districts of Timor-Lesté. A total of 3600 blood samples was collected from 1674 individual birds in 300 household chicken flocks during three sampling periods (December 2008–February 2009, March–May 2009, and June–August 2009). The mean interval between household visits was 101.6±1.9 days. None of the birds enrolled in the study was vaccinated against ND or AI. A haemagglutination inhibition (HI) test was used to determine antibody titres against ND virus and a competitive ELISA and HI tests were used to detect antibody against AI virus.The bird-level ND seroprevalence pooled across all samplings (adjusted for clustering by households) was 4.4% (95% CI 3.5–5.2). The bird-level ND seroprevalence in each of the three sampling periods (adjusted for clustering by household) was 3.0% (95% CI 2.0–4.0), 6.6% (95% CI 5.1–8.0) and 3.6 (95% CI 2.5–4.6), respectively. A total of 12.6% individual birds tested ND seropositive at least once over the total study period (95% CI 10.5–14.7).The flock-level ND seroprevalence (at least one bird tested had antibodies against ND virus) pooled across all samplings was 15.9% (95% CI 13.5–18.3). A total of 35.3% flocks had a minimum of one bird being ND seropositive at least once over the study period.The bird-level incidence rate for the period between the first and the second sampling and between the second and the third sampling was 5.6 (95% CI 4.1–7.5) and 0.5 (95% CI 0.5–3.8) per 10,000 bird-years-at-risk, respectively.A total of 1134 serum samples from the last sampling period between June and August 2009 was tested for antibodies against AI virus. Only 4 samples tested Influenza A positive, indicating a bird-level seroprevalence level for Influenza A of 0.4% (CI 0.0–0.7%). These Influenza A positive samples were further tested for HI antibodies against AI virus subtypes of H5N1, H5N3, H7N3 and H9N2, but all tested negative, suggesting that the influenza antibodies in those four birds resulted from exposure to low pathogenic AI viruses of different H subtypes.Our results indicate that village chickens in Timor-Lesté are exposed to ND virus; there was a higher risk of infection during the early months of 2009 than either immediately prior or subsequent to this. No evidence of infection of village chickens with H5, H7 or H9 AI viruses was detected in this study.

A Dual-Gate Field-Effect Transistor for Label-Free Electrical Detection of Avian Influenza

A dual-gate silicon nanowire field-effect transistor (FET) fabricated on a bulk substrate is designed to perform label-free electrical detection of the avian influenza antibody. A region of a FET channel that is conventionally covered by a gate electrode is intentionally left open in the dual-gate configuration, to provide a binding site for biological species. As a result, the channel potential at this open area is affected by the polarity and charge of the biological species that binds to the opened channel. The proposed device can be used as a biosensor by comparing its electrical characteristics before and after exposing the device to biological species of interest. This detection mechanism is verified using numerical simulation and by attaching charged polyelectrolytes (PAH and PSS) to the opened channel. Additionally, the avian influenza antibody is successfully detected without a labeling step using the proposed dual-gate FET. As a biomedical diagnostic tool, the proposed biosensor offers the advantages of label-free detection capability, low-cost compatibility with the complementary metal–oxide semiconductor fabrication process, and a read-out system for on-chip integration.

Evaluation of Oyster Mushroom (<i>Pleurotus Ostreatus</i>) as a Biological Growth Promoter on Performance, Humoral Immunity, and Blood Characteristics of Broiler Chicks

This study was conducted to determine the impacts of two levels of oyster mushroom (Pleurotus ostreatus) powder on productive and carcass traits, humoral immune responses, and blood characteristics of Ross 308 male broiler chicks reared to 42 d of age in comparison with a prebiotic supplement. Two hundred and forty, day-old male broiler chicks (Ross 308) were randomly assigned to one of four treatments with four replicates of 15 chicks based on a completely randomized design. The dietary treatments consisted of the basal diet as control, prebiotic group receiving 1 g/kg A-Max (Mannan-oligosaccharides), 10, and 20 g/kg oyster mushroom powder added to the basal diet. The obtained results showed that inclusion of 20 g/kg mushroom powder significantly improved body weight over the starter and grower (P<0.05) while feed efficiency was improved only over the starter (P<0.05) period compared to the control group. Considering the entire experimental period, (1-42 d) birds receiving prebiotic supplemented diets exhibited the highest body weight and lowest feed conversion ratio relative to the other treatments (P<0.05). Carcass yield and internal organs relative weights were not influenced by dietary treatments, but prebiotic supplementation significantly (P<0.05) decreased abdominal fat pad compared to the control group. Newcastle, influenza and sheep red blood cell antibody responses of chicks did not differ significantly at either level of inclusion of supplements. Chicks fed supplemented diets had the lowest serum triglyceride concentration at 42 day (P<0.05) compared to the control chicks, but other biochemical and hematological values tested including protein, albumin, globulin, high-density lipoprotein, low-density lipoprotein, and total cholesterol, red blood cell, white blood cell, hemoglobin and hematocrit were not markedly affected by treatments. In conclusion the obtained results indicated that oyster mushroom powder at an inclusion level of 20 g/kg of diet had favorable effects on performance criteria of chicks reared to 28 day of age while, prebiotic supplementation revealed its beneficial impact on chicks productive traits at slaughter age, besides reducing carcass abdominal fat and serum triglyceride concentration at 42 day.

Influenza vaccination during pregnancy: a systematic review of effectiveness and adverse effects.

Review question/objective Objectives: 1. To synthesise the best available evidence on the effectiveness of influenza vaccination during pregnancy, for pregnant women, her foetus and the child up to six months of age. 2. To synthesise the best available evidence on the types and frequency of adverse events for pregnant women, her foetus and the child up to six months of age, associated with influenza vaccination during pregnancy. Review questions: 1. What are the beneficial effects of influenza vaccination during pregnancy for pregnant women, her foetus and child up to six months of age? 2. What are the adverse effects of influenza vaccination during pregnancy for pregnant women, her foetus and child up to six months of age? Inclusion criteria Types of participants This study will focus on pregnant women with or without risk factors for complications from influenza infection, their unborn child that is being carried at the time of the vaccination, and children up to the age of 6 months. Types of intervention(s) Inactivated influenza vaccination, irrespective of antigenic configuration or adjuvant, administered via any route, any dose, to pregnant women of any trimester. Studies investigating the monovalent H1N1 vaccine will be assessed separately, as well as in combination with the standard trivalent vaccine. Comparator: Pregnant women not vaccinated against influenza. Types of outcomes •Number and severity of influenza and influenza-like episodes and hospitalisation from influenza for pregnant women and their infant less than six months. •Adverse effects for pregnant women, including but not limited to local reaction, fever, anaphylaxis, Guillain Barre Syndrome and maternal death. •Effects on the foetus, including but not limited to spontaneous abortion, stillbirth, premature birth, birth weight, foetal growth and congenital malformation. •Adverse effects of maternal immunisation on the infant up to six months of age. The case definition of influenza will be accepted as a collection of respiratory and systemic symptoms as defined by the author, and/or laboratory confirmed influenza using viral isolation and/or serology. Severity for the mother and infants will be assessed by hospitalisation and/or death, and/or severe disease such as pneumonia.

Integration of field effect transistor-based biosensors with a digital microfluidic device for a lab-on-a-chip application

A new platform for lab-on-a-chip system is suggested that utilizes a biosensor array embedded in a digital microfluidic device. With field effect transistor (FET)-based biosensors embedded in the middle of droplet-driving electrodes, the proposed digital microfluidic device can electrically detect avian influenza antibody (anti-AI) in real time by tracing the drain current of the FET-based biosensor without a labeling process. Digitized transport of a target droplet enclosing anti-AI from an inlet to the embedded sensor is enabled by the actuation of electrowetting-on-dielectrics (EWOD). A reduction of the drain current is observed when the target droplet is merged with a pre-existing droplet on the embedded sensor. This reduction of the drain current is attributed to the specific binding of the antigen and the antibody of the AI. The proposed hybrid device consisting of the FET-based sensor and an EWOD device, built on a coplanar substrate by monolithic integration, is fully compatible with current fabrication technology for control and read-out circuitry. Such a completely electrical manner of inducing the transport of bio-molecules, the detection of bio-molecules, the recording of signals, signal processing, and the data transmission process does not require a pump, a fluidic channel, or a bulky transducer. Thus, the proposed platform can contribute to the construction of an all-in-one chip.

Avian influenza H5 subtype antibodies in village chickens in four local government areas of Kaduna state, Nigeria

Aim: Biosecurity measures are rarely implemented in traditional farming systems especially in the villages. Given the importance of the village chickens as a source of income for rural families and its public health concern due to the frequent contact that exist between these birds and humans a study was conducted to assess the presence of antibodies to the H5 avian influenza virus subtype in village chickens in some Local Government Areas (LGAs) in Kaduna State. Materials and Methods: A total of 480 sera samples were obtained from apparently healthy local chickens in five LGAs where the avian influenza outbreak has not been reported. The sera were subjected to the Haemagglutination inhibition (HI) test using the H5N2 avian influenza antigen. Results: An overall prevalence of 2.9% with an individual seroprevalence of 10%, 0.8%, 4.1% and 3.3% in Jaba, Jemma\'a, Kaura and Zango Kataf local government areas respectively. There was no association between presence of pigs and detection of avian influenza antibodies, p=0.8723, OR 0.9153 (95% CI: 0.3108–2.695), but there was an association between presence of water birds (Gesse and Ducks) and detection of avian influenza antibodies, p= 0.0203, OR 3.488 (95% CI: 1.146–10.61). Conclusions: This result highlights the important role apparently healthy village chickens may play in virus perpetuation (reservoir) and in the spread of avian influenza to other animals and humans. An enhanced and sustained virological surveillance for the virus in village chickens was recommended.

Maternal Immune Response and Neonatal Seroprotection From a Single Dose of a Monovalent Nonadjuvanted 2009 Influenza A(H1N1) Vaccine

Pregnant women and infants who get influenza are at increased risk for severe illness. To evaluate the immunogenicity and transplacental antibody transfer of 2009 pandemic influenza A(H1N1) vaccine administered during pregnancy. Prospective, multicenter, single-group clinical trial. (ClinicalTrials.gov registration number: NCT01024400) Five level-3 perinatal centers in France. 107 pregnant women between 22(0/7) and 32(0/7) weeks of gestation. An intramuscular dose of a nonadjuvanted H1N1 vaccine that contained 15 mcg of hemagglutinin. Proportion of women with an influenza antibody titer of 1:40 or greater at days 21 and 42 after vaccination, delivery, and 3 months after delivery. Seroconversion rate, fold increase in the geometric mean titer 21 days after vaccination, and proportion of neonates with an antibody titer of 1:40 or greater at birth were also assessed. At baseline, 19% of the women had an antibody titer of 1:40 or greater. At day 21, 98% of the women had an antibody titer of 1:40 or greater, the seroconversion rate was 93%, and the fold increase in geometric mean titer was 67.4. At day 42, delivery, and 3 months after delivery, 98%, 92%, and 90% of the women, respectively, had an antibody titer of 1:40 or greater. Ninety-five percent of the cord serum samples obtained from 88 neonates showed an antibody titer of 1:40 or greater. The median neonate-mother antibody titer ratio was 1.4. Only healthy pregnant women were selected. Data on hemagglutination inhibition antibody titers of infants were reported only at birth. A single dose of a nonadjuvanted influenza A(H1N1) vaccine with 15 mcg of hemagglutinin triggered a strong immune response in pregnant women and a high rate of neonatal seroprotection. French National Institute of Health and Medical Research.

Immune response to influenza vaccination in children treated with methotrexate or/and tumor necrosis factor-α inhibitors

In children treated with immunosuppressive medication such as methotrexate and tumor necrosis factor-alpha (TNF-α) inhibitors, additional immunizations are recommended because of increased susceptibility to infections. However, it is unclear if adequate antibody response to vaccinations can be established in children receiving methotrexate and/or TNF-α inhibitors. In a prospective open label study, we assessed seroprotection and seroconversion following influenza vaccination during 2 seasons (6 strains) in 36 children with autoimmune disease treated either with methotrexate (n=18), TNF-α inhibitors (n=10) or both (n=8) and a control group of 16 immunocompetent children. Influenza antibody titers were determined by hemagglutinin inhibition assay, before and 4-8 weeks after vaccination. Post-vaccination seroprotection (defined as a titer ³1:40) did not significantly differ between immunosuppressed and immunocompetent subjects. Seroconversion, defined as the change from a nonprotective (

Obesity is associated with impaired immune response to influenza vaccination in humans

Background:Obesity is an independent risk factor for morbidity and mortality from pandemic influenza H1N1. Influenza is a significant public health threat, killing an estimated 250 000–500 000 people worldwide each year. More than one in ten of the world's adult population is obese and more than two-thirds of the US adult population is overweight or obese. No studies have compared humoral or cellular immune responses to influenza vaccination in healthy weight, overweight and obese populations despite clear public health importance.Objective:The study employed a convenience sample to determine the antibody response to the 2009–2010 inactivated trivalent influenza vaccine (TIV) in healthy weight, overweight and obese participants at 1 and 12 months post vaccination. In addition, activation of CD8+ T cells and expression of interferon-γ and granzyme B were measured in influenza-stimulated peripheral blood mononuclear cell (PBMC) cultures.Results:Body mass index (BMI) correlated positively with higher initial fold increase in IgG antibodies detected by enzyme-linked immunosorbent assay to TIV, confirmed by HAI antibody in a subset study. However, 12 months post vaccination, higher BMI was associated with a greater decline in influenza antibody titers. PBMCs challenged ex vivo with vaccine strain virus, demonstrated that obese individuals had decreased CD8+ T-cell activation and decreased expression of functional proteins compared with healthy weight individuals.Conclusion:These results suggest obesity may impair the ability to mount a protective immune response to influenza virus.

Immunogenicity of Trivalent Influenza Vaccine in Extremely Low-birth-weight, Premature Versus Term Infants

Influenza vaccine immunogenicity in premature infants is incompletely characterized. To assess the immunogenicity of trivalent, inactivated influenza vaccine (TIV) in extremely low-birth-weight (≤ 1000 g birth weight) premature (<30 weeks gestation) infants. We hypothesized that geometric mean titers of influenza antibody would be lower in premature than in full-term (FT) (≥ 37 week) infants. In this prospective multicenter study, former premature and FT infants who were 6 to 17 months of age received 2 doses of TIV during the 2006-2007 or 2007-2008 influenza seasons. Sera were drawn before dose 1, and 4 to 6 weeks after dose 2. Antibody was measured by hemagglutination inhibition. Over 2 years, 41 premature and 42 FT infants were enrolled; 36 and 33 of these infants, respectively, had postvaccination titers available. Premature infants weighed less (mean, 1.3-1.8 kg difference) at the time of immunization than FT infants. Prevaccination titers did not differ between groups. Premature infants had higher postvaccination antibody geometric mean titers than FT infants to H1 (2006-2007, 1:513 vs. 1:91, P = 0.03; 2007-2008, 1:363 vs. 1:189, P = 0.02) and B/Victoria (2006-2007, 1:51 vs. 1:10, P = 0.02). More premature than FT infants had antibody titers ≥ 1:32 to B/Victoria (85% vs. 60%, P = 0.04) in 2007-2008. Two (5%) premature and 8 (19%) FT infants had adverse events, primarily fever, within 72 hours after vaccination. No child had medically diagnosed influenza. Former premature infants had antibody responses to 2 TIV doses higher than or equal to those of FT children. Two TIV doses are immunogenic and well tolerated in extremely low-birth-weight, premature infants 6 to 17 months old.

Maternal Influenza Vaccination and Effect on Influenza Virus Infection in Young Infants

It is recommended that pregnant women receive influenza vaccine because of their increased risk for influenza complications. Several prospective US-based observational studies concluded that maternal influenza vaccination delays the age at first infection and reduces severity of influenza illness; one randomized trial reported that vaccination reduced the incidence of laboratory-confirmed influenza. This nonrandomized, prospective, observational cohort study investigated the effect of seasonal influenza vaccination in pregnant women on the occurrence of influenza virus infection in infants to 6 months of age. Participants were 1160 mother-infant pairs with mothers who delivered one infant during 3 influenza seasons between 2002 and 2005 at the Navajo and White Mountain Apache Indian reservations. Serum specimens from the infants of women who were unvaccinated (n = 587) and vaccinated (n = 573) were collected and analyzed. The primary study outcome measures in infants were laboratory-confirmed influenza, with influenza-like illness (ILI), ILI hospitalization, and elevated influenza hemagglutinin inhibition antibody titers. Among the 1160 infants, 193 (17%) were hospitalized for ILI, 412 (36%) had only an outpatient ILI visit, and 555 (48%) had no ILI episodes. The ILI incidence rate was 7.2 per 1000 person-days for infants born to unvaccinated women and 6.7 per 1000 person-days for those born to vaccinated women. Compared with infants of unvaccinated women, there was a 41% reduction in the risk of laboratory-confirmed influenza virus infection (relative risk, 0.59; 95% confidence interval, 0.37–0.93) and a 39% reduction in the risk of hospitalization for ILI (relative risk, 0.61; 95% confidence interval, 0.45–0.84) among infants of vaccinated women. Moreover, hemagglutinin inhibition antibody titers to each of the 8 influenza virus antigens tested at birth and at 2 to 3 months of age were significantly higher in infants born to mothers vaccinated during pregnancy. These findings show that maternal influenza vaccination increased influenza antibody titers in infants through 2 to 3 months of age, reducing their risk of both influenza virus infection and ILI hospitalization during the first 6 months of life. These data demonstrate the public health importance of maternal influenza vaccination.

Persistence of influenza vaccine-induced antibodies in lung transplant patients between seasons

Immunization policy-making bodies advised against immunizing too early before the influenza season because vaccine-specific antibody may wane before the end of the influenza season. Lung transplant patients are included in the group of high-risk patients for whom this recommendation had been made. We hypothesized that immunosuppressed lung transplant patients would maintain protective concentrations of influenza antigen-specific antibodies between seasons. As part of a planned 5-year study of influenza vaccine responses in lung transplant patients, we measured influenza antibody concentrations by hemagglutination inhibition assay before influenza immunization annually. The fraction of lung transplant patients who maintained seroprotective levels (≥ 40 hemagglutination units) approximately 11 months from last season immunization was calculated. Antibody concentrations and response rates in lung transplant patients were compared with healthy individuals and those waiting for lung transplantation. The majority of lung transplant patients maintained seroprotective influenza antigen-specific antibody concentrations for approximately 11 months after immunization. Seroprotection rates varied greatly with influenza antigens (healthy 68-100%, pretransplant 44-100%, transplant 64-100%), and were similar when groups were compared. More than 70% of lung transplant patients maintained seroprotective antibody concentrations to 10 of 11 vaccine antigens. Seroprotective influenza antibody concentrations are maintained at very high rates among immunosuppressed lung transplant patients and depend more on the vaccine virus than the immunostatus of the vaccine recipient. Early seasonal influenza immunization of lung transplant patients is appropriate.

Evaluation of Nobuto Filter Paper Strips for the Detection of Avian Influenza Virus Antibody in Waterfowl

The utility of using Nobuto paper strips for the detection of avian influenza antibodies was examined in mallards (Anas platyrhynchos) experimentally infected with low pathogenic avian influenza viruses. Blood was collected 2 wk after infection and was preserved either as serum or whole blood absorbed onto Nobuto strips. Analysis of samples using a commercially available blocking enzyme-linked immunosorbent assay revealed comparable results (> or = 96% sensitivity for all methods) between sera stored at -30 C and the Nobuto strip preservation method even when the Nobuto strips were stored up to 3 mo at room temperature (RT). Significant differences were detected in the ratio of sample absorbance to negative control absorbance for Nobuto strips stored at RT compared with sera stored at -30 C, although these differences did not affect the ability of the test to reliably detect positive and negative samples. Nobuto strips are a convenient and sensitive alternative to the collection of serum samples when maintaining appropriate storage temperatures is difficult.