Extensive CD4 and CD8 T Cell Cross-Reactivity between Alphaherpesviruses.

The Alphaherpesvirinae subfamily includes HSV types 1 and 2 and the sequence-divergent pathogen varicella zoster virus (VZV). T cells, controlled by TCR and HLA molecules that tolerate limited epitope amino acid variation, might cross-react between these microbes. We show that memory PBMC expansion with either HSV or VZV enriches for CD4 T cell lines that recognize the other agent at the whole-virus, protein, and peptide levels, consistent with bidirectional cross-reactivity. HSV-specific CD4 T cells recovered from HSV-seronegative persons can be explained, in part, by such VZV cross-reactivity. HSV-1-reactive CD8 T cells also cross-react with VZV-infected cells, full-length VZV proteins, and VZV peptides, as well as kill VZV-infected dermal fibroblasts. Mono- and cross-reactive CD8 T cells use distinct TCRB CDR3 sequences. Cross-reactivity to VZV is reconstituted by cloning and expressing TCRA/TCRB receptors from T cells that are initially isolated using HSV reagents. Overall, we define 13 novel CD4 and CD8 HSV-VZV cross-reactive epitopes and strongly imply additional cross-reactive peptide sets. Viral proteins can harbor both CD4 and CD8 HSV/VZV cross-reactive epitopes. Quantitative estimates of HSV/VZV cross-reactivity for both CD4 and CD8 T cells vary from 10 to 50%. Based on these findings, we hypothesize that host herpesvirus immune history may influence the pathogenesis and clinical outcome of subsequent infections or vaccinations for related pathogens and that cross-reactive epitopes and TCRs may be useful for multi-alphaherpesvirus vaccine design and adoptive cellular therapy.

Vaccinated children and adolescents with pertussis infections experience reduced illness severity and duration, Oregon, 2010-2012.

BACKGROUND: Bordetella pertussis causes severe respiratory illness among infants and adolescents. High proportions of breakthrough infection have been observed. To understand the effect of vaccination in the era of acellular pertussis vaccines (DTaP and Tdap), we assessed if vaccination status is associated with disease severity and duration. METHODS: The Multnomah County Health Department conducts enhanced pertussis surveillance for 1.7 million residents in the Portland, Oregon, metropolitan area. Surveillance activities include ascertaining demographics, clinical presentation, cough duration, vaccination history, and other health outcomes. Utilizing Advisory Committee on Immunization Practices (ACIP) routine vaccination recommendations, we analyzed a cohort of persons aged 6 weeks to 18 years with confirmed pertussis to assess illness severity and duration by vaccination status. Analysis was conducted using both logistic regression (disease severity) and survival analysis (cough duration). RESULTS: During 2010-2012, 98.7% (n = 624) of patients with confirmed pertussis in our cohort had vaccination, treatment, demographic, and outcome information. Among these patients, 45% (n = 286) were ACIP up to date with vaccinations. Ever-vaccinated cases were significantly less likely to be hospitalized or develop severe illness (adjusted odds ratio [aOR], 0.2; 95% confidence interval [CI], .1-.8 and aOR, 0.4; 95% CI, .2-.9, respectively). ACIP up-to-date patients stopped coughing significantly more rapidly than unvaccinated patients (adjusted hazard ratio, 1.7; 95% CI, 1.3-2.2). CONCLUSIONS: Patients with pertussis vaccination had decreased morbidity characterized by less severe illness and significantly reduced illness duration. Therefore, vaccination is recommended among at-risk individuals, and research into the nature of the residual vaccine immunity is warranted.

Travel-associated antimicrobial drug-resistant nontyphoidal Salmonellae, 2004-2009.

To evaluate trends in and risk factors for acquisition of antimicrobial-drug resistant nontyphoidal Salmonella infections, we searched Oregon surveillance data for 2004-2009 for all culture-confirmed cases of salmonellosis. We defined clinically important resistance (CIR) as decreased susceptibility to ampicillin, ceftriaxone, ciprofloxacin, gentamicin, or trimethoprim/sulfamethoxazole. Of 2,153 cases, 2,127 (99%) nontyphoidal Salmonella isolates were obtained from a specific source (e.g., feces, urine, blood, or other normally sterile tissue) and had been tested for drug susceptibility. Among these, 347 (16%) isolates had CIR. The odds of acquiring CIR infection significantly increased each year. Hospitalization was more likely for patients with than without CIR infections. Among patients with isolates that had been tested, we analyzed data from 1,813 (84%) who were interviewed. Travel to eastern or Southeast Asia was associated with increased CIR. Isolates associated with outbreaks were less likely to have CIR. Future surveillance activities should evaluate resistance with respect to international travel.

A 2-substituted prodiginine, 2-(p-hydroxybenzyl)prodigiosin, from Pseudoalteromonas rubra.

In the course of work aimed at the discovery of new pharmaceutical lead compounds from marine bacteria, a lipophilic extract of the bacterium Pseudoalteromonas rubra displayed significant cytotoxicity against SKOV-3, a human ovarian adenocarcinoma cell line. Bioassay-directed fractionation of this extract resulted in the isolation of a series of known and new prodiginine-type azafulvenes. The structure of the major metabolite was elucidated by interpretation of spectroscopic data as a 2-substituted prodigiosin, which we named 2-(p-hydroxybenzyl)prodigiosin (HBPG).