Axial CT scan of the neck showing the grossly enlarged and irregular epiglottis with bilateral cervical lymphadenopathy

<p><b>Copyright information:</b></p><p>Taken from "Atypical presentation of HIV in a pregnant patient"</p><p></p><p>The Ulster medical journal 2006;75(2):160-161.</p><p>Published online Jan 2006</p><p>PMCID:PMC1891733.</p><p>© The Ulster Medical Society, 2006</p

Heterologous Prime-Boost Vaccination with MF59-Adjuvanted H5 Vaccines Promotes Antibody Affinity Maturation towards the Hemagglutinin HA1 Domain and Broad H5N1 Cross-Clade Neutralization

In an open label clinical study (2007), MF59-adjuvanted hemagglutinin (HA) vaccine from H5N1-A/Vietnam/1194/2004 (clade 1) was administered to subjects previously vaccinated (primed) with clade 0 H5N3 (A/duck/Singapore/97) vaccine at least 6 years earlier (in 1999 or 2001). The primed individuals responded rapidly and generated high neutralizing antibody titers against the H5N1-Vietnam strain within 7 days of a single booster vaccination. Furthermore, significant cross-neutralization titers were measured against H5N1 clade 0, 1, and 2 viruses. In the current study, the impact of MF59 adjuvant during heterologous priming on the quality of humoral polyclonal immune response in different vaccine arms were further evaluated using real time kinetics assay by surface plasmon resonance (SPR). Total anti-H5N1 HA1 polyclonal sera antibody binding from the heterologous prime-boost groups after a single MF59-H5N1 boost was significantly higher compared with sera from unprimed individuals that received two MF59-H5N1 vaccinations. The antigen-antibody complex dissociation rates (surrogate for antibody affinity) of the polyclonal sera against HA1 of H5N1-A/Vietnam/1194/2004 from the MF59-H5N3 primed groups were significantly higher compared to sera from unadjuvanted primed groups or unprimed individuals that received two MF59-H5N1 vaccines. Furthermore, strong inverse correlations were observed between the antibody dissociation off-rates of the immune sera against HA1 (but not HA2) and the virus neutralization titers against H5 vaccine strains and heterologous H5N1 strains. These findings supports the use of oil-in-water-adjuvanted pandemic influenza vaccines to elicit long term memory B cells with high affinity BCR capable of responding to potential variant pandemic viruses likely to emerge and adapt to human transmissions

Geometric Mean and Standard deviations for the end-point microneutralization titers of three vaccine groups against diverse H5N1 virus strains.

a<p>MN Data are shown for post-H5N1 vaccination sera collected on day 21 following single H5N1 booster vaccination from the MF59-adjuvanted primed and nonadjuvanted primed or after two vaccinations in the unprimed control vaccine group.</p>b<p>Percentage of responders (fraction of subjects) demonstrating MN titers of ≥1∶40 are shown in the parenthesis.</p

Binding of post-H5N1 vaccination polyclonal human serum to properly folded HA1 protein.

<p>Steady-state equilibrium analysis of the total binding antibodies in the polyclonal human vaccine sera to properly folded functional H5N1-A/Vietnam/1203/2004 HA1-His₆ was measured by SPR. Ten-fold diluted individual post-boost H5N1 vaccination sera from the three vaccine groups were injected simultaneously onto HA1 immobilized on a sensor chip through the free amine group and onto a blank flow cell, free of peptide. Maximum resonance unit (Max RU) values for HA1 binding by serum antibodies obtained from multiple individuals from either MF59-adjuvanted H5N3-primed (red symbols; average-1703 RU) or unadjuvanted H5N3-primed (green symbols; average-1408 RU) on day 21 following single booster vaccination or unprimed controls after 2 doses of MF-59-adjuvanted H5N1 vaccine (blue symbols; average-982 RU). The binding antibodies in the H5N3-primed vaccine groups were significantly higher compared to the unprimed vaccine group.</p

Serum antibody off-rates to H5-Viet-rHA1 (but not rHA2) following heterologous prime-boost strongly correlate with the <i>in-vitro</i> neutralizing capacity against the homologous H5 vaccine viruses.

<p>Antibody off-rate constants were determined directly from the plasma sample interaction with H5N1 rHA1 or rHA2 protein using SPR in the dissociation phase. SPR analysis of post-boost vaccination human sera from all vaccine groups included in the vaccine trial was performed with rHA1 (A and B) or rHA2 (C and D) of the H5N1- A/Vietnam/1203/2004 strain. Each symbol represents one individual. Serum samples on day 21 following single H5N1 booster vaccination from the MF59-H5N3 adjuvanted primed (red symbols) or unadjuvanted H5N3 primed (green symbols) or after two MF59-H5N1 vaccinations in the unprimed control (blue symbols) vaccine group is shown. Antibody affinity of post-H5N1 vaccinated human sera against HA1 (but not HA2) of H5N1- A/Vietnam/1203/2004 correlated with the homologous MN titers against the A/Vietnam/1203/2004 (H5N1) booster vaccine virus (A) as well as A/duck/Singapore/1997 (H5N3) priming vaccine virus (B).</p

Multi-Centre Observational Study of Transplacental Transmission of Influenza Antibodies following Vaccination with AS03(A)-Adjuvanted H1N1 2009 Vaccine

Introduction: Illness and death from influenza increase during pregnancy. In the United Kingdom pregnant women were targeted in a national programme for vaccination during the H1N1 2009–10 pandemic. Methods: In this study, pregnant women were recruited in labour from November 9, 2009 to March 10, 2010. Pandemic vaccination status was determined. Venous cord blood collected at delivery was evaluated for transplacental transfer of antibodies by measurement of haemagglutination inhibition and microneutralization titres. Results: Samples were collected from 77 vaccinated and 27 unvaccinated women. Seroprotection (HI titre ≥1:40) was detected in 58 (75.3%, 95% CI 64.2–84.4) cord blood samples from vaccinated women and 5 (18.5%, 95% CI 6.3–38.1) from unvaccinated women (P<0.0001). There was evidence of transplacental seroprotection 8 days after maternal immunization (77.9%, 95 CI 66.2–87.1), maintained in most cases for at least 16 weeks. Discussion: Immunization of pregnant women with AS03A-adjuvanted vaccine is followed by transplacental transfer of passive immunity at titres consistent with clinical protection in three-quarters of new-born infants. The findings support national and international pandemic H1N1 2009 recommendations for immunization during pregnancy

Multi-Centre Observational Study of Transplacental Transmission of Influenza Antibodies following Vaccination with AS03_A-Adjuvanted H1N1 2009 Vaccine

<div><h3>Introduction</h3><p>Illness and death from influenza increase during pregnancy. In the United Kingdom pregnant women were targeted in a national programme for vaccination during the H1N1 2009–10 pandemic.</p> <h3>Methods</h3><p>In this study, pregnant women were recruited in labour from November 9, 2009 to March 10, 2010. Pandemic vaccination status was determined. Venous cord blood collected at delivery was evaluated for transplacental transfer of antibodies by measurement of haemagglutination inhibition and microneutralization titres.</p> <h3>Results</h3><p>Samples were collected from 77 vaccinated and 27 unvaccinated women. Seroprotection (HI titre ≥1∶40) was detected in 58 (75.3%, 95% CI 64.2–84.4) cord blood samples from vaccinated women and 5 (18.5%, 95% CI 6.3–38.1) from unvaccinated women (P<0.0001). There was evidence of transplacental seroprotection 8 days after maternal immunization (77.9%, 95 CI 66.2–87.1), maintained in most cases for at least 16 weeks.</p> <h3>Discussion</h3><p>Immunization of pregnant women with AS03_A-adjuvanted vaccine is followed by transplacental transfer of passive immunity at titres consistent with clinical protection in three-quarters of new-born infants. The findings support national and international pandemic H1N1 2009 recommendations for immunization during pregnancy.</p> </div

Boxplot GMT haemagglutinination inhibition titre by interval from maternal vaccination to delivery.

<p>(Titres are expressed as reciprocal of the dilution and are given on a log₂ scale.).</p

Baseline characteristics of vaccinated and unvaccinated mothers [33].

<p>Data are means for: years/birth weight/gestational age (95% confidence interval) or number (%) for all other parameters.</p

Reverse cumulative distribution curves of haemagglutinination inhibition and microneutralization antibody titres in cord blood serum samples.

<p>(Titres are expressed as reciprocal of the dilution and are given on a log₂ scale.) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0047448#pone.0047448-Puleston1" target="_blank">[33]</a>.</p