Longitudinal landscapes of serum antibody repertoires after influenza infection and vaccination

Vaccination is the most effective means of infectious disease prevention. Despite its success, however, we still lack a clear understanding of vaccine responses in humans. For example, influenza vaccines still leave a large fraction of population vulnerable. Over the past decade, single B-cell analysis and next-generation sequencing (NGS) technologies have become invaluable tools for studying the antibody repertoire to influenza. Such studies have led to discoveries of broadly-neutralizing antibodies (bNAbs), which can neutralize across multiple strains of influenza virus, promoting the notion of designing a universal vaccine that will elicit such antibodies. One of such isolated bNAbs, called FI6, showed remarkable ability to neutralize all of the influenza A virus strains through targeting the conserved epitope in the stem of hemagglutinin (HA). However, it remains unclear whether such bNAbs actually play a role in conferring protection against influenza since antibody proteins (not B-cells) need to circulate at physiologically relevant concentrations in serum to have implications in protection. Using high-resolution proteomics coupled with NGS, we quantitatively determined the serological antibody repertoire to CA09 HA (H1) at the individual clonotype-level in a donor (whom FI6 was isolated from) following influenza infection (in 2010 with pandemic CA09) and vaccination across five years (2010-2014 with seasonal flu vaccine). We analyzed the temporal changes of head-targeting and stem-binding antibodies, illustrating the gradual increase of stem-targeting antibodies following repeated exposures to CA09 HA. Following vaccination in 2014, \u3e60% of the repertoire consisted of one single clonotype of stem-binding antibody that was present at very low abundance in 2010. Our data demonstrate that the repetitive exposure to influenza skews the serological repertoire toward antibodies that target conserved epitopes, and these antibodies continue to be boosted every time the same epitopes are encountered. Once elicited, stem-binding antibodies displayed a tendency to persist in serum across multiple years while head-specific antibodies decayed quicker. The differential longevity of stem-binding and head-specific antibodies presented here has direct implications for the design of the future universal vaccine

Endemic fungal infections in solid organ and hematopoietic cell transplant recipients enrolled in the Transplant‐Associated Infection Surveillance Network ( TRANSNET )

Background Invasive fungal infections are a major cause of morbidity and mortality among solid organ transplant ( SOT ) and hematopoietic cell transplant ( HCT ) recipients, but few data have been reported on the epidemiology of endemic fungal infections in these populations. Methods Fifteen institutions belonging to the Transplant‐Associated Infection Surveillance Network prospectively enrolled SOT and HCT recipients with histoplasmosis, blastomycosis, or coccidioidomycosis occurring between March 2001 and March 2006. Results A total of 70 patients (64 SOT recipients and 6 HCT recipients) had infection with an endemic mycosis, including 52 with histoplasmosis, 9 with blastomycosis, and 9 with coccidioidomycosis. The 12‐month cumulative incidence rate among SOT recipients for histoplasmosis was 0.102%. Occurrence of infection was bimodal; 28 (40%) infections occurred in the first 6 months post transplantation, and 24 (34%) occurred between 2 and 11 years post transplantation. Three patients were documented to have acquired infection from the donor organ. Seven SOT recipients with histoplasmosis and 3 with coccidioidomycosis died (16%); no HCT recipient died. Conclusions This 5‐year multicenter prospective surveillance study found that endemic mycoses occur uncommonly in SOT and HCT recipients, and that the period at risk extends for years after transplantation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106980/1/tid12186.pd

Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium.

BACKGROUND: Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential. METHODS: To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved. RESULTS: There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses. CONCLUSIONS: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk

Measurements of the Branching Fractions and Helicity Amplitudes in B --> D* rho Decays

Using 9.1 fb-1 of e+ e- data collected at the Upsilon(4S) with the CLEO detector using the Cornell Electron Storage Ring, measurements are reported for both the branching fractions and the helicity amplitudes for the decays B- -> D*0 rho- and B0bar -> D*+ rho-. The fraction of longitudinal polarization in B0bar -> D*+ rho- is found to be consistent with that in B0bar -> D*+ l- nubar at q^2 = M^2_rho, indicating that the factorization approximation works well. The longitudinal polarization in the B- mode is similar. The measurements also show evidence of non-trivial final-state interaction phases for the helicity amplitudes.Comment: 11 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PR

Branching Fractions of tau Leptons to Three Charged Hadrons

From electron-positron collision data collected with the CLEO detector operating at CESR near \sqrt{s}=10.6 GeV, improved measurements of the branching fractions for tau decays into three explicitly identified hadrons and a neutrino are presented as {\cal B}(\tau^-\to\pi^-\pi^+\pi^-\nu_\tau)=(9.13\pm0.05\pm0.46)%, {\cal B}(\tau^-\to K^-\pi^+\pi^-\nu_\tau)=(3.84\pm0.14\pm0.38)\times10^{-3}, {\cal B}(\tau^-\to K^-K^+\pi^-\nu_\tau)=(1.55\pm0.06\pm0.09)\times10^{-3}, and {\cal B}(\tau^-\to K^-K^+K^-\nu_\tau)<3.7\times10^{-5} at 90% C.L., where the uncertainties are statistical and systematic, respectively.Comment: 10 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, to appear in Phys. Rev. Let

First Observation of barB0 to D*0 pi+pi+pi-pi- Decays

We report on the observation of B0bar -> D*0 pi+ pi+ pi- pi- decays. The branching ratio is (0.30 +/- 0.07 +/- 0.06)%. Interest in this particular mode was sparked by Ligeti, Luke and Wise who propose it as a way to check the validity of factorization tests in B0bar -> D*+ pi+ pi- pi- pi0 decays.Comment: 11 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, Version to appear in Phys. Rev.

The Search for eta(1440) --> K^0_S K^pm \pi^mp in Two-Photon Fusion at CLEO

We analyze 13.8 \rm fb^{-1} of the integrated e^+e^- luminosity collected at 10.6 GeV center-of-mass energy with the CLEO II and CLEO II.V detectors to study exclusive two-photon production of hadrons with masses below 1.7{\rm \ GeV/c^2} decaying into the K^0_S K^\pm \pi^\mp final state. We observe two statistically significant enhancements in the \eta(1440) mass region. These enhancements have large transverse momentum which rules them out as being due to pseudoscalar resonances but is consistent with the production of axial-vector mesons. We use tagged two-photon events to study the properties of the observed enhancements and associate them with the production of f_1(1285) and f_1(1420). Our non-observation of \eta(1440) is inconsistent by more than two standard deviations with the first observation of this resonance in two-photon collisions by the L3 experiment. We present our estimates for 90% confidence level upper limits on the products of two-photon partial widths of pseudoscalar hadrons and their branching fractions into K^0_S(\pi^+\pi^-)K^\pm\pi^\mp.Comment: 24 pages postscript,also available through http://www.lns.cornell.edu/public/CLNS/2004/, submitted to PR

New Measurements of Upsilon(1S) Decays to Charmonium Final States

Using substantially larger data samples collected by the CLEO III detector, we report on new measurements of the decays of Upsilon(1S) to charmonium final states, including J/Psi, psi(2S), and chi_cJ. The latter two are first observations of these decays. We measure the branching fractions as follows: B(Y(1S)--> J/Psi+X)=(6.4+-0.4+-0.6)x10^-4, B(Y(1S)--> psi(2S)+X)/B(Y(1S)--> J/Psi+X)=0.41+-0.11+-0.08, B(Y(1S)--> chi_c1+X)/B(Y(1S)--> J/Psi+X)=0.35+-0.08+-0.06, B(Y(1S)--> chi_c2+X)/B(Y(1S)--> J/Psi+X)=0.52+-0.12+-0.09, and B(Y(1S)--> chi_c0+X)/B(Y(1S)--> J/Psi+X)<7.4% at 90% confidence level. We also report on the momentum and angular spectra of J/Psi's in Upsilon(1S) decay. The results are compared to predictions of the color octet and color singlet models.Comment: 27 pages postscript,also available through http://w4.lns.cornell.edu/public/CLNS/, submitted to PR