Immunologic profiling of the infant immune response to whole-cell and acellular pertussis vaccines.

Despite robust antibody responses, immunity induced by acellular pertussis vaccine (DTaP) wanes over time and risk of pertussis seems to be lower in children who receive whole-cell vaccine (DTP) as their first dose. To interrogate the early immunologic response to pertussis vaccine, we enrolled 56 healthy infants who received either DTP or DTaP at 2-, 4-, 6-, and 18-months of age. RNA-sequencing and ribosome profiling of PBMC were performed prior to vaccination (Day 1) and on either Day 2 or Day 8.

Structural mapping of polyclonal IgG responses to HA after influenza virus vaccination or infection.

Cellular and molecular characterization of immune responses elicited by influenza virus infection and seasonal vaccination have informed efforts to improve vaccine efficacy, breadth, and longevity. Here, we use negative stain electron microscopy polyclonal epitope mapping (nsEMPEM) to structurally characterize the humoral IgG antibody responses to hemagglutinin (HA) from human patients vaccinated with a seasonal quadrivalent flu vaccine or infected with influenza A viruses. Our data show that both vaccinated and infected patients had humoral IgGs targeting highly conserved regions on both H1 and H3 subtype HAs, including the stem and anchor, which are targets for universal influenza vaccine design.

Structural Mapping of Polyclonal IgG Responses to HA After Influenza Virus Vaccination or Infection.

Cellular and molecular characterization of immune responses elicited by influenza virus infection and seasonal vaccination have informed efforts to improve vaccine efficacy, breadth, and longevity. Here, we use negative stain electron microscopy polyclonal epitope mapping (nsEMPEM) to structurally characterize the humoral IgG antibody responses to hemagglutinin (HA) from human patients vaccinated with a seasonal quadrivalent flu vaccine or infected with influenza A viruses. Our data show that both vaccinated and infected patients had humoral IgGs targeting highly conserved regions on both H1 and H3 subtype HAs, including the stem and anchor, which are targets for universal influenza vaccine design.

Metabolomic Signatures Differentiate Immune Responses in Avian Influenza Vaccine Recipients.

Background: Avian influenza viruses pose significant risk to human health. Vaccines targeting the hemagglutinin of these viruses are poorly immunogenic without the use of adjuvants.

Methods: Twenty healthy men and women (18-49 years of age) were randomized to receive 2 doses of inactivated influenza A/H5N1 vaccine alone (IIV) or with AS03 adjuvant (IIV-AS03) 1 month apart.

Safety and immunogenicity of live, attenuated intranasal Bordetella pertussis vaccine (BPZE1) in healthy adults.

Background: BPZE1 is a live, attenuated pertussis vaccine derived from B. pertussis strain Tohama I modified by genetic removal or inactivation of 3 B. pertussis toxins: pertussis toxin, dermonecrotic toxin, and tracheal cytotoxin.

Neutralizing COVID-19 Convalescent Plasma in Adults Hospitalized With COVID-19: A Blinded, Randomized, Placebo-Controlled Trial.

Background: Convalescent plasma has been one of the most common treatments for COVID-19, but most clinical trial data to date have not supported its efficacy.

Research Question: Is rigorously selected COVID-19 convalescent plasma with neutralizing anti-SARS-CoV-2 antibodies an efficacious treatment for adults hospitalized with COVID-19?

Study Design And Methods: This was a multicenter, blinded, placebo-controlled randomized clinical trial among adults hospitalized with SARS-CoV-2 infection and acute respiratory symptoms for < 14 days. Enrolled patients were randomly assigned to receive one unit of COVID-19 convalescent plasma (n = 487) or placebo (n = 473).

Humoral and cellular immune responses to the SARS-CoV-2 BNT162b2 vaccine among a cohort of solid organ transplant recipients and healthy controls.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with increased morbidity and mortality in solid organ transplant (SOT) recipients. Despite exclusion from SARS-CoV-2 vaccine clinical trials, these individuals were identified as high-risk and prioritized for vaccination in public health guidelines.

Methods: We prospectively evaluated humoral and cellular immune responses to two doses of the SARS-CoV-2 mRNA vaccine, BNT162b2, in 56 SOT recipients and 26 healthy controls (HCs).

Balanced Cellular and Humoral Immune Responses Targeting Multiple Antigens in Adults Receiving a Quadrivalent Inactivated Influenza Vaccine.

The role of T cell immunity has been acknowledged in recent vaccine development and evaluation. We tested the humoral and cellular immune responses to Flucelvax, a quadrivalent inactivated seasonal influenza vaccine containing two influenza A (H1N1 Singapore/GP1908/2015 IVR-180 and H3N2 North Carolina/04/2016) and two influenza B (Iowa/06/2017 and Singapore/INFTT-16-0610/2016) virus strains, using peripheral blood mononuclear cells stimulated by pools of peptides overlapping all the individual influenza viral protein components. Baseline reactivity was detected against all four strains both at the level of CD4 and CD8 responses and targeting different proteins.

A high-throughput liquid bead array assay confirms strong correlation between SARS-CoV-2 antibody level and COVID-19 severity.

A detailed understanding of the adaptive host response to SARS-CoV-2 infection in humans is urgently needed. We developed a sensitive, high-throughput, and efficient assay using liquid bead array technology. We observed advantages over traditional ELISA for the detection and quantification of binding IgG against the receptor binding domain (RBD) of SARS-CoV-2.

Reactogenicity and immunogenicity of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) in pregnant and nonpregnant women.

Objective: Tetanus toxoid, reduced diphtheria toxoid, and acellular pertusiss (Tdap) vaccine is recommended during each pregnancy, regardless of prior receipt. Data on reactogenicity and immunogenicity, particularly after repeated Tdap, are limited. We compared local injection-site and systemic reactions and serologic response following Tdap in (1) pregnant and nonpregnant women and (2) pregnant women by self-reported prior Tdap receipt.

A randomized, placebo-controlled phase I trial of live, attenuated herpes zoster vaccine in subjects with end-stage renal disease immunized prior to renal transplantation.

Background: Solid organ transplant recipients are at increased risk for reactivation of herpes zoster, or shingles, and have a higher frequency of serious complications including post-herpetic neuralgia. A live, attenuated shingles vaccine is effective and approved for individuals 50 years and older. The vaccine is contraindicated following transplantation, but may be used in patients with renal failure.

Pertussis seroepidemiology in women and their infants in Sarlahi District, Nepal.

Background: Infants are at greatest risk for pertussis morbidity and mortality. Maternal vaccination during pregnancy has been shown to prevent pertussis in young infants in high- and middle-income countries. However, data on the levels of maternal pertussis antibodies and the efficiency of transplacental transfer in low-income South Asian settings are limited.

Greater activation of peripheral T follicular helper cells following high dose influenza vaccine in older adults forecasts seroconversion.

Background: Influenza related morbidity and mortality disproportionately impacts older adults. The serologic response to vaccine is diminished in older adults; however, high dose inactivated influenza vaccine (HD IIV) has shown improved rates of seroconversion compared to standard dose (SD IIV). We hypothesize this may be due to the superior ability of high dose vaccine to activate T follicular helper (Tfh) cells and provide B cell dependent T cell help.

H7N9 influenza virus neutralizing antibodies that possess few somatic mutations.

Avian H7N9 influenza viruses are group 2 influenza A viruses that have been identified as the etiologic agent for a current major outbreak that began in China in 2013 and may pose a pandemic threat. Here, we examined the human H7-reactive antibody response in 75 recipients of a monovalent inactivated A/Shanghai/02/2013 H7N9 vaccine. After 2 doses of vaccine, the majority of donors had memory B cells that secreted IgGs specific for H7 HA, with dominant responses against single HA subtypes, although frequencies of H7-reactive B cells ranged widely between donors.

Tissue-specific regulatory T cells: biomarker for acute graft-vs-host disease and survival.

Regulatory T cells (Tregs) are a subset of CD4(+) T cells that are characterized by the expression of CD25 and Foxp3 and are capable of suppressing alloimmune responses. We assessed whether high frequencies of circulating skin or gut tissue-specific Tregs at engraftment could predict acute graft-vs-host disease (aGVHD) incidence and survival in a cohort of hematopoietic cell transplant (HCT) recipients. Tregs were analyzed at engraftment in 74 patients receiving HCT.

Predicting posttransplantation diabetes mellitus by regulatory T-cell phenotype: implications for metabolic intervention to modulate alloreactivity.

Chronic inflammation and decreased frequency of regulatory T cells (Tregs) in visceral adipose tissue contribute to the propagation of insulin resistance to diabetes mellitus. We tested the hypothesis that new-onset posttransplantation diabetes mellitus (PTDM) is associated with measurable changes in Treg subsets after allogeneic hematopoietic stem cell transplantation (HSCT). PTDM before day 100 and Treg phenotype at engraftment were determined in 36 HSCT recipients without preceding history of diabetes mellitus.

Comparative study of different sources of pertussis toxin (PT) as coating antigens in IgG anti-PT enzyme-linked immunosorbent assays.

In an effort to improve the reliability and reproducibility of serological assays for Bordetella pertussis, a collaborative study was conducted to compare four different sources of pertussis toxin (PT) as coating antigens in the immunoglobulin G (IgG) anti-PT enzyme-linked immunosorbent assay (ELISA). Four sources of PT were used as coating antigens in the IgG anti-PT ELISA in four different testing laboratories (labs A to D) to determine whether the different antigen preparations and different laboratories influenced assay results. A panel of 60 sera consisting of deidentified human specimens from previous vaccination trials of healthy adults and infants and clinical specimens from outbreak settings was tested.

Identification of potential human respiratory syncytial virus and metapneumovirus T cell epitopes using computational prediction and MHC binding assays.

Human respiratory syncytial virus (RSV) and human metapneumovirus (MPV) are two of the most common causes of serious viral lower respiratory tract illness in humans. CD8+ T cells have been shown to be important in animal models and human clinical studies for the clearance of viral infection, and they may contribute in part to protection against severe disease during reinfections. Precise enumeration and accurate phenotyping of RSV- or MPV-specific CD8+ T cells in humans is currently limited by the relatively small number of T cell epitopes that have been mapped with accompanying identification of MHC restriction patterns.

Antibodies recognizing protective pertussis toxin epitopes are preferentially elicited by natural infection versus acellular immunization.

Despite more than 50 years of vaccination, disease caused by the bacterium Bordetella pertussis persists, with rates increasing in industrialized countries over the past decade. This rise may be attributed to several factors, including increased surveillance, emergence of vaccine escape variants, waning immunity in adults, and the introduction of acellular subunit vaccines, which include chemically detoxified pertussis toxin (PTd). Two potently protective epitopes on pertussis toxin (PTx) are recognized by the monoclonal antibodies 1B7 and 11E6, which inhibit catalytic and cell-binding activities, respectively.

Effect of allergen challenge on the percentage of natural killer T cells in patients with atopic asthma.

Background: Invariant natural killer T (iNKT) cells produce cytokines that can influence the immune response to infection or allergen. Controversy surrounds their role in exacerbations of human atopic asthma.

Objectives: To determine the effect of allergen challenge on iNKT cells' mobilization to the airways and blood and to establish the relationship between airway iNKT cells and bronchial sensitivity to methacholine and allergen in patients with atopic asthma.

Cellular immunity in adolescents and adults following acellular pertussis vaccine administration.

Cell-mediated immune (CMI) responses to an acellular pertussis vaccine administered to 49 subjects, a subset of participants in the National Institutes of Health-funded adult acellular pertussis vaccine efficacy trial, were evaluated and compared with antibody responses to vaccine antigens. Levels of proliferation of and cytokine secretion from lymphocytes cultured in the presence of pertussis toxin, filamentous hemagglutinin, or pertactin were measured before vaccination and 1 month and 1 year after vaccination. Statistically significant increases in lymphocyte stimulation indices and cytokine secretion were noted at both 1 month and 1 year after vaccination.