Antibody responses to influenza A(H1N1)pdm infection.
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ABSTRACT:
SUBMITTER: Wraith S
PROVIDER: S-EPMC7707244 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Human antibody responses against the 2009 pandemic H1N1 (pH1N1) virus are predominantly directed against conserved epitopes in the stalk and receptor-binding domain of the hemagglutinin (HA) protein. This is in stark contrast to pH1N1 antibody responses generated in ferrets, which are focused on the variable Sa antigenic site of HA. Here, we show that most humans born between 1983 and 1996 elicited pH1N1 antibody responses that are directed against an epitope near the HA receptor-binding domain. Importantly, most individuals born before 1983 or after 1996 did not elicit pH1N1 antibodies to this HA epitope. The HAs of most seasonal H1N1 (sH1N1) viruses that circulated between 1983 and 1996 possess a critical K133 amino acid in this HA epitope, whereas this amino acid is either mutated or deleted in most sH1N1 viruses circulating before 1983 or after 1996. We sequentially infected ferrets with a 1991 sH1N1 virus and then a pH1N1 virus. Sera isolated from these animals were directed against the HA epitope involving amino acid K133. These data suggest that the specificity of pH1N1 antibody responses can be shifted to epitopes near the HA receptor-binding domain after sequential infections with sH1N1 and pH1N1 viruses that share homology in this region.
| S-EPMC3727314 | biostudies-literature
Project description:Although some adults infected with influenza 2009 A(H1N1)pdm09 viruses mounted high hemagglutination inhibition (HAI) antibody response, they still suffered from severe disease, or even death. Here, we analyzed antibody profiles in patients (n = 31, 17-65 years) admitted to intensive care units (ICUs) with lung failure and invasive mechanical ventilation use due to infection with A(H1N1)pdm09 viruses during 2009-2011. We performed a comprehensive analysis of the quality and quantity of antibody responses using HAI, virus neutralization, biolayer interferometry, enzyme-linked-lectin and enzyme-linked immunosorbent assays. At time of the ICU admission, 45% (14/31) of the patients had HAI antibody titers ≥ 80 in the first serum (S1), most (13/14) exhibited narrowly-focused HAI and/or anti-HA-head binding antibodies targeting single epitopes in or around the receptor binding site. In contrast, 42% (13/31) of the patients with HAI titers ≤ 10 in S1 had non-neutralizing anti-HA-stem antibodies against A(H1N1)pdm09 viruses. Only 19% (6/31) of the patients showed HA-specific IgG1-dominant antibody responses. Three of 5 fatal patients possessed highly focused cross-type HAI antibodies targeting the (K130 + Q223)-epitopes with extremely low avidity. Our findings suggest that narrowly-focused low-quality antibody responses targeting specific HA-epitopes may have contributed to severe infection of the lower respiratory tract.
| S-EPMC9440095 | biostudies-literature
Project description:Following the emergence and global spread of a novel H1N1 influenza virus in 2009, two A(H1N1)pdm/09 influenza vaccines produced from the A/California/07/09 H1N1 strain were selected and used for the national immunisation programme in the United Kingdom: an adjuvanted split virion vaccine and a non-adjuvanted whole virion vaccine. In this study, we assessed the immune responses generated in inbred large white pigs (Babraham line) following vaccination with these vaccines and after challenge with A(H1N1)pdm/09 virus three months post-vaccination. Both vaccines elicited strong antibody responses, which included high levels of influenza-specific IgG1 and haemagglutination inhibition titres to H1 virus. Immunisation with the adjuvanted split vaccine induced significantly higher interferon gamma production, increased frequency of interferon gamma-producing cells and proliferation of CD4(-)CD8(+) (cytotoxic) and CD4(+)CD8(+) (helper) T cells, after in vitro re-stimulation. Despite significant differences in the magnitude and breadth of immune responses in the two vaccinated and mock treated groups, similar quantities of viral RNA were detected from the nasal cavity in all pigs after live virus challenge. The present study provides support for the use of the pig as a valid experimental model for influenza infections in humans, including the assessment of protective efficacy of therapeutic interventions.
| S-EPMC3302873 | biostudies-literature
Project description:IntroductionThe 2009 swine-origin H1N1 influenza virus (swH1N1) provided an opportunity to study immune responses to a new influenza strain in the context of seasonal influenza vaccination. Our goals were: to assess whether analyzing multiple parameters of immune responsiveness to influenza has an advantage over evaluating hemagglutination inhibition (HAI) titer alone, to determine whether vaccination with the seasonal vaccine induced cross-reactive immunity to swH1N1 in some individuals, and to determine whether the immune response against swH1N1 is higher after infection than vaccination.MethodsAntibody and T cell responses were studied in ten subjects who were first immunized with the 2009-2010 seasonal influenza subunit vaccine, then 6 weeks later with the swH1N1 monovalent subunit vaccine. The amount of antibody against native virus glycoproteins, overall avidity of these antibodies, and HAI titer were measured. T cells were evaluated for proliferation and IFNγ secretion in response to the vaccine in vitro. Individuals with influenza-like illness were also evaluated, adding a microplate neuraminidase inhibition (NAI) test.ResultsThe immune response to influenza was highly variable and immune parameters did not increase in parallel. The seasonal vaccine induced antibodies recognizing the pandemic virus in 50% of subjects. Antibody affinity and NAI activity to swH1N1 were higher after natural infection than vaccination.ConclusionsThe evaluation of several immune parameters gives a more complete measure of immune responsiveness to influenza infection or vaccination than the HAI test alone.
| S-EPMC3197711 | biostudies-literature
Project description:The vaccination program against the 2009 pandemic H1N1 influenza virus (2009 H1N1) provided a unique opportunity to determine if immune responses to the 2009 H1N1 vaccine were affected by a recent, prior vaccination against seasonal influenza virus. In the present study, we studied the immune responses to the 2009 H1N1 vaccine in subjects who either received the seasonal influenza virus vaccination within the prior 3 months or did not. Following 2009 H1N1 vaccination, subjects previously given a seasonal influenza virus vaccination exhibited significantly lower antibody responses, as determined by hemagglutination inhibition assay, than subjects who had not received the seasonal influenza virus vaccination. This result is compatible with the phenomenon of "original antigenic sin," by which previous influenza virus vaccination hampers induction of immunity against a new variant. Our finding should be taken into account for future vaccination programs against pandemic influenza virus outbreaks.
| S-EPMC3165229 | biostudies-literature
Project description:After the influenza H1N1 pandemic of 2009, the seasonal A/Brisbane/59/2007 strain was replaced by the A/California/07/2009 strain for the influenza virus vaccine composition. After several seasons with no indications on the occurrence of antigenic drift, A/Michigan/45/2015 was chosen as the H1N1 vaccine strain for the 2017/2018 season. Since the immune response to influenza is shaped by the history of exposure to antigenically similar strains, the potential cross-protection between seasonal human influenza vaccine strains and the emerging pandemic strains was investigated. Human serum samples were tested by hemagglutination inhibition and single radial hemolysis assays against A/Brisbane/59/2007, A/California/07/2009, and A/Michigan/45/2015 strains. Strong cross-reactions between A/California/07/2009 and A/Michigan/45/2015 strains were observed in 2009/2010, most likely induced by the start of the 2009 pandemic, and the subsequent post-pandemic seasons from 2010/2011 onward when A/California/07/2009 became the predominant strain. In the 2014/2015 season, population immunity against A/California/07/2009 and A/Michigan/45/2015 strains increased again, associated with strong cross-reactions. Whereas hemagglutination inhibition assay has a higher sensitivity for detection of new seasonal drift, the single radial hemolysis assay is an excellent tool for determining the presence of pre-existing immunity, allowing a potential prediction on the booster potential of influenza vaccines against newly emerging drifted strains.
| S-EPMC7712556 | biostudies-literature
Project description:Immune imprinting is a driver known to shape the anti-hemagglutinin (HA) antibody landscape of individuals born within the same birth cohort. With the HA and neuraminidase (NA) proteins evolving at different rates under immune selection pressures, anti-HA and anti-NA antibody responses since childhood influenza virus infections have not been evaluated in parallel at the individual level. This is partly due to the limited knowledge of changes in NA antigenicity, as seasonal influenza vaccines have focused on generating neutralizing anti-HA antibodies against HA antigenic variants. Here, we systematically characterized the NA antigenic variants of seasonal A(H1N1) viruses from 1977 to 1991 and completed the antigenic profile of N1 NAs from 1977 to 2015. We identified that NA proteins of A/USSR/90/77, A/Singapore/06/86, and A/Texas/36/91 were antigenically distinct and mapped N386K as a key determinant of the NA antigenic change from A/USSR/90/77 to A/Singapore/06/86. With comprehensive panels of HA and NA antigenic variants of A(H1N1) and A(H1N1)pdm09 viruses, we determined hemagglutinin inhibition (HI) and neuraminidase inhibition (NI) antibodies from 130 subjects born between 1950 and 2015. Age-dependent imprinting was observed for both anti-HA and anti-NA antibodies, with the peak HI and NI titers predominantly detected from subjects at 4 to 12 years old during the year of initial virus isolation, except the age-independent anti-HA antibody response against A(H1N1)pdm09 viruses. More participants possessed antibodies that reacted to multiple antigenically distinct NA proteins than those with antibodies that reacted to multiple antigenically distinct HA proteins. Our results support the need to include NA proteins in seasonal influenza vaccine preparations. IMPORTANCE Seasonal influenza vaccines have aimed to generate neutralizing anti-HA antibodies for protection since licensure. More recently, anti-NA antibodies have been established as an additional correlate of protection. While HA and NA antigenic changes occurred discordantly, the anti-HA and anti-NA antibody profiles have rarely been analyzed in parallel at the individual level, due to the limited knowledge on NA antigenic changes. By characterizing NA antigenic changes of A(H1N1) viruses, we determined the anti-HA and anti-NA antibody landscape against antigenically distinct A(H1N1) and A(H1N1)pdm09 viruses using sera of 130 subjects born between 1950 and 2015. We observed age-dependent imprinting of both anti-HA and anti-NA antibodies against strains circulated during the first decade of life. A total of 67.7% (88/130) and 90% (117/130) of participants developed cross-reactive antibodies to multiple HA and NA antigens at titers ≥1:40. With slower NA antigenic changes and cross-reactive anti-NA antibody responses, including NA protein in influenza vaccine preparation may enhance vaccine efficacy.
| S-EPMC10294682 | biostudies-literature
Project description:BackgroundThe ability of influenza vaccines to elicit CD4(+) T cells and the relationship between induction of CD4(+) T cells and vaccine-induced neutralizing antibody responses has been controversial. The emergence of swine-origin 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) provided a unique opportunity to examine responses to an influenza vaccine composed of both novel and previously encountered antigens and to probe the relationship between B-cell and T-cell responses to vaccination.MethodsWe tracked CD4(+) T-cell and antibody responses of human subjects vaccinated with monovalent subunit A(H1N1)pdm09 vaccine. The specificity and magnitude of the CD4(+) T-cell response was evaluated using cytokine enzyme-linked immunosorbent spot assays in conjugation with peptide pools representing distinct influenza virus proteins.ResultsOur studies revealed that vaccination induced readily detectable CD4(+) T cells specific for conserved portions of hemagglutinin (HA) and the internal viral proteins. Interestingly, expansion of HA-specific CD4(+) T cells was most tightly correlated with the antibody response.ConclusionsThese results indicate that CD4(+) T-cell expansion may be a limiting factor in development of neutralizing antibody responses to pandemic influenza vaccines and suggest that approaches to facilitate CD4(+) T-cell recruitment may increase the neutralizing antibody produced in response to vaccines against novel influenza strains.
| S-EPMC3532833 | biostudies-literature
Project description:Proteomics data from lungs and trachea of ferrets (Mustela putorius furo) infected intranasally with either influenza A/California/04/2009 (CA04) virus or influenza A/Brevig Mission/1/1918 (1918) virus. Sections of trachea and lung collected were at 1, 3 and 8 days post-infection.
2015-04-24 | MSV000079114 | MassIVE
Project description:Reliable discrimination of recent influenza A infection from previous exposure using hemagglutination inhibition (HI) or virus neutralization tests is currently not feasible. This is due to low sensitivity of the tests and the interference of antibody responses generated by previous infections. Here we investigate the diagnostic characteristics of a newly developed antibody (HA1) protein microarray using data from cross-sectional serological studies carried out before and after the pandemic of 2009. The data are analysed by mixture models, providing a probabilistic classification of sera (susceptible, prior-exposed, recently infected). Estimated sensitivity and specificity for identifying A/2009 infections are low using HI (66% and 51%), and high when using A/2009 microarray data alone or together with A/1918 microarray data (96% and 95%). As a heuristic, a high A/2009 to A/1918 antibody ratio (>1.05) is indicative of recent infection, while a low ratio is indicative of a pre-existing response, even if the A/2009 titer is high. We conclude that highly sensitive and specific classification of individual sera is possible using the protein microarray, thereby enabling precise estimation of age-specific infection attack rates in the population even if sample sizes are small.
| S-EPMC4236143 | biostudies-literature