Cross-Neutralizing Antibodies to Pandemic 2009 H1N1 and Recent Seasonal H1N1 Influenza A Strains Influenced by a Mutation in Hemagglutinin Subunit 2

Pandemic 2009 H1N1 influenza A virus (2009 H1N1) differs from H1N1 strains that circulated in the past 50 years, but resembles the A/New Jersey/1976 H1N1 strain used in the 1976 swine influenza vaccine. We investigated whether sera from persons immunized with the 1976 swine influenza or recent seasonal influenza vaccines, or both, neutralize 2009 H1N1. Using retroviral pseudovirions bearing hemagglutinins on their surface (HA-pseudotypes), we found that 77% of the sera collected in 1976 after immunization with the A/New Jersey/1976 H1N1 swine influenza vaccine neutralized 2009 H1N1. Forty five percent also neutralized A/New Caledonia/20/1999 H1N1, a strain used in seasonal influenza vaccines during the 2000/01–2006/07 seasons. Among adults aged 48–64 who received the swine influenza vaccine in 1976 and recent seasonal influenza vaccines during the 2004/05–2008/09 seasons, 83% had sera that neutralized 2009 H1N1. However, 68% of age-matched subjects who received the same seasonal influenza vaccines, but did not receive the 1976 swine influenza vaccine, also had sera that neutralized 2009 H1N1. Sera from both 1976 and contemporary cohorts frequently had cross-neutralizing antibodies to 2009 H1N1 and A/New Caledonia/20/1999 that mapped to hemagglutinin subunit 2 (HA2). A conservative mutation in HA2 corresponding to a residue in the A/Solomon Islands/3/2006 and A/Brisbane/59/2007 H1N1 strains that circulated in the 2006/07 and 2007/08 influenza seasons, respectively, abrogated this neutralization. These findings highlight a cross-neutralization determinant influenced by a point mutation in HA2 and suggest that HA2 may be evolving under direct or indirect immune pressure

I kappa B kinase alpha (IKKα) activity is required for functional maturation of dendritic cells and acquired immunity to infection

Dendritic cells (DC) are required for priming antigen-specific T cells and acquired immunity to many important human pathogens, including Mycobacteriuim tuberculosis (TB) and influenza. However, inappropriate priming of auto-reactive T cells is linked with autoimmune disease. Understanding the molecular mechanisms that regulate the priming and activation of naïve T cells is critical for development of new improved vaccines and understanding the pathogenesis of autoimmune diseases. The serine/threonine kinase IKKα (CHUK) has previously been shown to have anti-inflammatory activity and inhibit innate immunity. Here, we show that IKKα is required in DC for priming antigen-specific T cells and acquired immunity to the human pathogen Listeria monocytogenes. We describe a new role for IKKα in regulation of IRF3 activity and the functional maturation of DC. This presents a unique role for IKKα in dampening inflammation while simultaneously promoting adaptive immunity that could have important implications for the development of new vaccine adjuvants and treatment of autoimmune diseases

Housing change of chronic schizophrenic patients: A consequence of the revolving door

A study of 119 chronic schizophrenics discharged to the community revealed that by 1 year post release, 50% have changed their living arrangement at least once. Housing changes, which typically involved movement from one non-institutional living situation to another, followed rehospitalization episodes and appear to be a consequence of the revolving door phenomenon. By virtue of its impact on rehospitalization, interpersonal stress in the patient's living environment has an indirect effect on housing change. The remarkable frequency with which housing changes occur among the mentally ill in both sheltered care and non-institutional living settings deserves consideration in the planning of mental health and social welfare service for this constituency.

Childhood Experiences and Current Adjustment of Offspring of Indigent Patients With Schizophrenia

OBJECTIVE: This study reports the childhood experiences, current life situation and level of adjustment, and prior mental health service use of offspring of indigent people with schizophrenia. METHODS: Sixty-eight patient-parents were asked for consent for researchers to contact their adolescent and adult offspring. Thirty-nine consenting offspring were interviewed with an assessment battery that included measures of current occupational and social functioning, psychiatric status, and mental health service use. RESULTS: Interviewed offspring were raised in an average of three different settings from birth to 18 years of age. Relatives, particularly grandparents and aunts, were more likely to provide surrogate parenting than were nonkin foster parents and were more significant nurturing figures than biological parents. The typical offspring had a high school diploma, was gainfully employed, and was involved with a spouse or household partner or had a close friend. Twenty-three of the 39 offspring had children, and most were raising their children alone. Ten offspring had a diagnosis of major depression, schizoaffective disorder, or drug or alcohol abuse, but none had a diagnosis of schizophrenia. Four of the ten offspring with a psychiatric diagnosis had never been treated. CONCLUSIONS: Findings underscore the need for long-term studies of families with a parent who is a psychiatric patient. Rehabilitation efforts should include extended family who play a critical role in raising offspring during periods when patient-parents are unable to do so. Offspring should be included in efforts to educate families about schizophrenia