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Antibody response to influenza A(H1N1)pdm09 in vaccinated, serologically infected and unaffected pregnant women and their newborns.

ABSTRACT: To evaluate the serological response in pregnant Danish women immunized during the 2009 pandemic by serologic infection or by vaccination with influenza A(H1N1) Pandemrix(®) and describe levels of passively acquired maternal antibody in their offspring.Observational cohort study.Department of Obstetrics, Aarhus University Hospital, Skejby, Denmark, October to December 2009.Pregnant women and their offspringSerological analysis of antibodies to influenza A(H1N1)pdm09 by hemagglutination inhibition assay in 197 women and their offspring. Blood samples were collected consecutively at delivery from the mother and the umbilical cord. In a subgroup of 124 of the 197 women, an additional blood sample from gestational weeks 9-12 was available for analysis.Seroconversion, geometric mean titer, geometric mean-fold rise and protective antibodies.33 of the 124 subgroup women (27%) seroconverted during pregnancy, 79% after vaccination and 17% after serologic infection (p < 0.001). The geometric mean titer after delivery in non-vaccinated, non-serologically infected women was 17.1 (95%CI 15.7-18.6). The geometric mean titer increased significantly after serologic infection with H1N1 [76.5 (95%CI 51.3-113.9), p < 0.001] and after vaccination [589.6 (95%CI 339.3-1024.7), p < 0.001]. The geometric mean-fold rise (mother at delivery/mother early pregnancy) was significantly higher after vaccination [2.23 (1.93-2.54)] than after serologic infection [1.73 (1.59-1.87), p = 0.013]. In newborns of vaccinated mothers, 89.5% had protective antibody levels compared with 15.8% in newborns of serologically infected mothers (p < 0.001).Influenza vaccination during pregnancy confers passive immunity to the newborn.

SUBMITTER: Helmig RB

PROVIDER: S-EPMC4745092 | biostudies-other | 2015 Aug

REPOSITORIES: biostudies-other

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Project description:Influenza viruses cause seasonal outbreaks and pose a continuous pandemic threat. Although vaccines are available for influenza control, their efficacy varies each season and a vaccine for a novel pandemic virus manufactured using current technology will not be available fast enough to mitigate the effect of the first pandemic wave. Antivirals can be effective against many different influenza viruses but have not thus far been used extensively for outbreak control. Baloxavir, a recently licensed antiviral drug that targets the influenza virus endonuclease, has been shown to reduce virus shedding more effectively than oseltamivir, a widely used neuraminidase inhibitor drug. Thus it is possible that treatment with baloxavir might also interrupt onward virus transmission. To test this, we utilized the ferret model, which is the most commonly used animal model to study influenza virus transmission. We established a subcutaneous baloxavir administration method in ferrets which achieved similar pharmacokinetics to the approved human oral dose. Transmission studies were then conducted in two different locations with different experimental setups to compare the onward transmission of A(H1N1)pdm09 virus from infected ferrets treated with baloxavir, oseltamivir or placebo to naïve sentinel ferrets exposed either indirectly in adjacent cages or directly by co-housing. We found that baloxavir treatment reduced infectious viral shedding in the upper respiratory tract of ferrets compared to placebo, and reduced the frequency of transmission amongst sentinels in both experimental setups, even when treatment was delayed until 2 days post-infection. In contrast, oseltamivir treatment did not substantially affect viral shedding or transmission compared to placebo. We did not detect the emergence of baloxavir-resistant variants in treated animals or in untreated sentinels. Our results support the concept that antivirals which decrease viral shedding could also reduce influenza transmission in the community.

Project description:ObjectivesTo review neurological complications after the influenza A (H1N1) pdm09, highlighting the clinical differences between patients with post-vaccine or viral infection.DesignA search on Medline, Ovid, EMBASE, and PubMed databases using the keywords “neurological complications of Influenza AH1N1” or “post-vaccine Influenza AH1N1.”SettingOnly papers written in English, Spanish, German, French, Portuguese, and Italian published from March 2009 to December 2012 were included.SampleWe included 104 articles presenting a total of 1636 patient cases. In addition, two cases of influenza vaccine-related neurological events from our neurological care center, arising during the period of study, were also included.Main outcome measuresDemographic data and clinical diagnosis of neurological complications and outcomes: death, neurological sequelae or recovery after influenza A (H1N1) pdm09 vaccine or infection.ResultsThe retrieved cases were divided into two groups: the postvaccination group, with 287 patients, and the viral infection group, with 1349 patients. Most patients in the first group were adults. The main neurological complications were Guillain-Barre syndrome (GBS) or polyneuropathy (125), and seizures (23). All patients survived. Pediatric patients were predominant in the viral infection group. In this group, 60 patients (4.7%) died and 52 (30.1%) developed permanent sequelae. A wide spectrum of neurological complications was observed.ConclusionsFatal cases and severe, permanent, neurological sequelae were observed in the infection group only. Clinical outcome was more favorable in the post-vaccination group. In this context, the relevance of an accurate neurological evaluation is demonstrated for all suspicious cases, as well as the need of an appropriate long-term clinical and imaging follow-up of infection and post-vaccination events related to influenza A (H1N1) pdm09, to clearly estimate the magnitude of neurological complications leading to permanent disability.

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.

Project description:BackgroundNon-neutralizing antibodies inducing complement-dependent lysis (CDL) and antibody-dependent cell-mediated cytotoxicity (ADCC) activity may contribute to protection against influenza infection. We investigated CDL and ADCC responses in healthy adults randomized to receive either non-adjuvanted or AS03-adjuvanted monovalent A(H1N1)pdm09 vaccine (containing 15 µg/3.75 ?g of hemagglutinin, respectively) on a 2-dose schedule 21 days apart.MethodsWe conducted an exploratory analysis of a subset of 106 subjects having no prior history of A(H1N1)pdm09 infection or seasonal influenza vaccination enrolled in a previously reported study (NCT00985673). Antibody responses against the homologous A/California/7/2009 (H1N1) vaccine strain and a related A/Brisbane/59/2007 (H1N1) seasonal influenza strain were analyzed up to Day 42.ResultsBaseline seropositivity determined with hemagglutination inhibition (HI), CDL and ADCC antibody titers against viral strains was high; A/California/7/2009 (HI [40.4-48.1%]; CDL [34.6-36.0%]; ADCC [92.1-92.3%]); A/Brisbane/59/2007 (HI [73.1-88.9%]; CDL [38.0-42.0%]; ADCC [86.8-97.0%]). CDL seropositivity increased following vaccination with both adjuvanted and non-adjuvanted formulations (A/California/7/2009 [95.9-100%]; A/Brisbane/59/2007 [75.5-79.6%]). At Day 21, increases in CDL and ADCC antibody geometric mean titers against both strains were observed for both formulations. After 2 doses of AS03-adjuvanted vaccine, vaccine responses of 95.8% (?9-fold increase from baseline in CDL titers) and 34.3% (?16-fold increase from baseline in ADCC titers) were seen against A/California/7/2009; and 22.4% and 42.9%, respectively, against A/Brisbane/59/2007. Vaccine responses after 2 doses of the non-adjuvanted vaccine were broadly similar.ConclusionsBroadly comparable non-neutralizing immune responses were observed following vaccination with non-adjuvanted and AS03-adjuvanted A(H1N1)pdm09 formulations; including activity against a related vaccine strain.

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Antibody response to influenza A(H1N1)pdm09 in vaccinated, serologically infected and unaffected pregnant women and their newborns.

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