Jean Handy

Obesity is associated with impaired immune response to influenza vaccination in humans

Background:Obesity is an independent risk factor for morbidity and mortality from pandemic influenza H1N1. Influenza is a significant public health threat, killing an estimated 250 000–500 000 people worldwide each year. More than one in ten of the worlds adult population is obese and more than two-thirds of the US adult population is overweight or obese. No studies have compared humoral or cellular immune responses to influenza vaccination in healthy weight, overweight and obese populations despite clear public health importance.Objective:The study employed a convenience sample to determine the antibody response to the 2009–2010 inactivated trivalent influenza vaccine (TIV) in healthy weight, overweight and obese participants at 1 and 12 months post vaccination. In addition, activation of CD8+ T cells and expression of interferon-γ and granzyme B were measured in influenza-stimulated peripheral blood mononuclear cell (PBMC) cultures.Results:Body mass index (BMI) correlated positively with higher initial fold increase in IgG antibodies detected by enzyme-linked immunosorbent assay to TIV, confirmed by HAI antibody in a subset study. However, 12 months post vaccination, higher BMI was associated with a greater decline in influenza antibody titers. PBMCs challenged ex vivo with vaccine strain virus, demonstrated that obese individuals had decreased CD8+ T-cell activation and decreased expression of functional proteins compared with healthy weight individuals.Conclusion:These results suggest obesity may impair the ability to mount a protective immune response to influenza virus.

Host nutritional status: the neglected virulence factor.

The emergence of new infectious diseases and old diseases with new pathogenic properties is a burgeoning worldwide problem. Severe acute respiratory syndrome (SARS) and acquired immune deficiency syndrome (AIDS) are just two of the most widely reported recent emerging infectious diseases. What are the factors that contribute to the rapid evolution of viral species? Various hypotheses have been proposed, all involving opportunities for virus spread (for example, agricultural practices, climate changes, rainforest clearing or air travel). However, the nutritional status of the host, until recently, has not been considered a contributing factor to the emergence of infectious disease. In this review, we show that host nutritional status can influence not only the host response to the pathogen, but can also influence the genetic make-up of the viral genome. This latter finding markedly changes our concept of host–pathogen interactions and creates a new paradigm for the study of such phenomena.

The Role of Oxidative Stress in Viral Infections

Abstract: Oxidative stress is implicated as a pathogenic factor in a number of viral infections. Our work has shown that nutritionally induced oxidative stress exacerbates the pathogenesis of coxsackievirus B3 (CVB3) infection in mice. Of particular note, mice fed on a diet deficient in antioxidants developed myocarditis when infected with a normally benign strain of CVB3. This change in virulence was found to be due to changes in the viral genome. Immune functions of the oxidatively stressed mice were also altered. Another example of the effect of oxidative stress on a viral pathogen took place in Cuba in the 1990s. An epidemic of optic and peripheral neuropathy in the population occurred that was associated with a lack of dietary antioxidants and with smoking (a pro‐oxidant). A coxsackie‐like virus was isolated from the cerebrospinal fluid from 84% of patients cultured. Thus, oxidative stress can have profound effects, not only on the host, but on the pathogen as well.

Overweight and obese adult humans have a defective cellular immune response to pandemic H1N1 influenza A virus

Obese adults have a greater risk of morbidity and mortality from infection with pandemic H1N1 influenza A virus (pH1N1). The objective of the present study was to elucidate the specific mechanisms by which obesity and overweight impact the cellular immune response to pH1N1.

Cytomegalovirus viremia, mortality, and end-organ disease among patients with AIDS receiving potent antiretroviral therapies.

Objective:To determine the association of cytomegalovirus (CMV) viremia with CMV disease and death in patients with AIDS. Design and setting:Prospective, observational cohort study conducted at a university hospital. Methods:A cohort of 190 subjects with AIDS who were CMV seropositive and had no history or evidence of CMV disease were longitudinally evaluated for signs and symptoms of CMV disease and CMV viremia with plasma CMV DNA polymerase chain reaction (PCR) and whole blood CMV hybrid capture. Results:A total of 187 subjects had at least 1 study visit following entry. At baseline, the median CD4+ cell count and plasma HIV RNA level were 110/μL (range = 3-620/μL) and 47,973 copies/mL (<30- >750,000 copies/mL), respectively. Highly active antiretroviral therapy (HAART) use increased from 87.5% during the 1st study year to 98.5% by the end of the study. During a median follow-up of 334 days, 16% (30) of the subjects died and 2 (6%) developed CMV disease. No deaths were attributable to CMV disease; 4 subjects who died developed CMV prior to death. Baseline HIV viral load and final CD4+ cell count were significantly and independently associated with mortality. Detectable plasma CMV DNA PCR was an independent predictor of death even after adjusting for HIV RNA level and CD4+ cell count prior to death (P = 0.038). In contrast, whole blood CMV hybrid capture did not predict mortality. The CMV assays neither collectively nor individually were found to be associated with the few cases of CMV disease. Conclusions:In patients with AIDS and seropositive for CMV, detection of CMV viremia with plasma CMV DNA PCR was predictive of death and provided additional prognostic information on the risk of all cause-mortality beyond that obtained with CD4+ cell count and HIV viral load testing alone. Detection of CMV viremia by plasma with CMV DNA PCR in patients with AIDS, particularly those with low CD4+ cell counts, provides additional rationale for optimization of antiretroviral therapy and consideration for preemptive anti-CMV therapy.

Functional markers of selenium status: UK Food Standards Agency workshop report.

The workshop was organised to discuss the validity and limitations of existing functional markers of Se status in human subjects and to identify future research priorities in this area. Studies presented as part of this workshop investigated: the bioavailability of Se from different dietary sources; potential functional markers of Se status; individual variation in response to Se; the effect of marginal Se status on immune function. The workshop highlighted the need to define the relationship between functional markers of Se status and health outcomes.

Psychoimmunology and aids: Psychological distress and herpes simplex virus in human immunodeficiency virus infected individuals

Abstract No studies investigating the relationship of herpesviruses and psychological distress in Human Immunodeficiency Virus (HIV) infection are available in the literature. Antibody titers for Cytomegalovirus (CMV), Epstein-Barr (EBV) and Herpes Simplex virus (HSV) were assessed from sera drawn at the lime of psychological testing for one hundred HIV seropositive subjects. Increased psychological distress was correlated with increased titers of antibody to HSV, but not to CMV or EBV. Psychological distress may play a role in the devastating HSV infections experienced by immune deficient individuals. A stress mediated reactivation/potentiation hypothesis is discussed, where distress reactivates latent HSV which in turn potentiates HIV replication. These results may have implications for treatment of individuals co-infected with HIV and HSV.

The antibody response to influenza vaccination is not impaired in type 2 diabetics

BACKGROUND Diabetics are considered to be at high risk for complications from influenza infection and type 2 diabetes is a significant comorbidity of obesity. Obesity is an independent risk factor for complications from infection with influenza. Annual vaccination is considered the best strategy for protecting against influenza infection and its complications. Our previous study reported intact antibody responses 30 days post vaccination in an obese population. This study was designed to determine the antibody response to influenza vaccination in type 2 diabetics. METHODS Subjects enrolled were 18 or older without immunosuppressive diseases or taking immunosuppressive medications. A pre-vaccination blood draw was taken at time of enrollment, the subjects received the influenza vaccine and returned 28-32 days later for a post-vaccination blood draw. Height and weight were also obtained at the first visit and BMI was calculated. Antibody levels to the vaccine were determined by both ELISA and hemagglutination inhibition (HAI) assays. RESULTS As reported in our previous work, obesity positively correlates with the influenza antibody response (p=0.02), while age was negatively correlated with antibody response (p<0.001). In both year 1 and year 2 of our study there was no significant difference in the percentage of the type 2 diabetic subjects classified as seroprotected or a responder to the influenza vaccine compared to the non-diabetic subjects. CONCLUSIONS These data are important because they demonstrate that diabetics, considered a high risk group during influenza season, are able to mount an antibody response to influenza vaccination that may protect them from influenza infection.