Effects of Human Respiratory Syncytial Virus, Metapneumovirus, Parainfluenza Virus 3 and Influenza Virus on CD4+ T Cell Activation by Dendritic Cells

BACKGROUND: Human respiratory syncytial virus (HRSV), and to a lesser extent human metapneumovirus (HMPV) and human parainfluenza virus type 3 (HPIV3), re-infect symptomatically throughout life without antigenic change, suggestive of incomplete immunity. One causative factor is thought to be viral interference with dendritic cell (DC)-mediated stimulation of CD4+ T cells. METHODOLOGY, PRINCIPAL FINDINGS: We infected human monocyte-derived DC with purified HRSV, HMPV, HPIV3, or influenza A virus (IAV) and compared their ability to induce activation and proliferation of autologous CD4+ T cells in vitro. IAV was included because symptomatic re-infection without antigenic change is less frequent, suggesting that immune protection is more complete and durable. We examined virus-specific memory responses and superantigen-induced responses by multiparameter flow cytometry. Live virus was more stimulatory than inactivated virus in inducing DC-mediated proliferation of virus-specific memory CD4+ T cells, suggesting a lack of strong suppression by live virus. There were trends of increasing proliferation in the order: HMPV<HRSV<HPIV3<IAV, and greater production of interferon-γ and tumor necrosis factor-α by proliferating cells in response to IAV, but differences were not significant. Exposure of DC to HRSV, HPIV3, or IAV reduced CD4+ T cell proliferation in response to secondary stimulus with superantigen, but the effect was transitory and greatest for IAV. T cell cytokine production was similar, with no evidence of Th2 or Th17 skewing. CONCLUSIONS, SIGNIFICANCE: Understanding the basis for the ability of HRSV in particular to symptomatically re-infect without significant antigenic change is of considerable interest. The present results show that these common respiratory viruses are similar in their ability to induce DC to activate CD4+ T cells. Thus, the results do not support the common model in which viral suppression of CD4+ T cell activation and proliferation by HRSV, HMPV, and HPIV3 is a major factor in the difference in re-infectability compared to IAV

Biological characterization of clones derived from the edmonston strain of measles virus in comparison with schwarz and CAM-70 vaccine strains

Four virus clones were derived from the Edmonston strain of measles virus by repeated plaque purification. These clones were compared with the vaccine strains Schwarz and CAM-70 in terms of biological activities including plaque formation, hemagglutination, hemolysis and replication in Vero cells and chick embryo fibroblasts (CEF). Two clones of intermediate plaque yielded mixed plaque populations on subcultivation whereas the other two, showing small and large plaque sizes, showed stable plaque phenotypes. The vaccine strains showed consistent homogeneous plaque populations. All the Edmonston clones showed agglutination of monkey erythrocytes in isotonic solution while both vaccine strains hemagglutinated only in the presence of high salt concentrations. Variation in the hemolytic activity was observed among the four clones but no hemolytic activity was detected for the vaccine virus strains. Vaccine strains replicated efficiently both in Vero cells and CEF. All four clones showed efficient replication in Vero cells but different replication profiles in CEF. Two of them replicated efficiently, one was of intermediate efficiency and the other showed no replication in CEF. Two of the clones showed characteristics similar to vaccine strains. One in terms of size and homogeneity of plaques, the other for a low hemolytic activity and both for the efficiency of propagation in CEF

Drug Saf

INTRODUCTION: Hepatitis B (HB) vaccination programs were set up worldwide in the early 1990s. Despite their major focus on reducing the burden of HB infection, they have seldom achieved the targeted population coverage in most countries, including the USA, with around 24.5% of adults being vaccinated against HB. Among proposed reasons for this is the persisting doubt about a possible link between HB vaccination and the occurrence of cases of multiple sclerosis (MS). OBJECTIVE: Our objective was to evaluate a potential safety signal between MS and HB vaccination. We conducted a disproportionality analysis (DPA) using the cases reported to the Vaccine Adverse Event Reporting System (VAERS). METHODS: We calculated the proportional reporting rate (PRR) and reporting odds ratio (ROR) of MS having occurred within the 120 days following HB immunization in adults aged 19-49 years when compared with other vaccines using the reports recorded in the VAERS database. Both ratios were estimated globally and then according to the origin of reports (USA vs. non-USA). We then performed a sensitivity analysis using a broader category of demyelinating events. FINDINGS: MS cases following HB vaccination were more likely to originate from outside the USA and to be reported before 2000 than those associated with other immunizations. All computed ratios were found to be statistically significant, with PRRs ranging from 3.48 to 5.56 and RORs ranging from 3.48 to 5.62. When considering the geographical origin, similar RORs were obtained for both US and non-US cases. CONCLUSION: In VAERS, MS cases were up to five times more likely to be reported after an HB vaccination than after any other vaccination. Since DPA is mainly suited for hypothesis generation, further studies evaluating the nature of the link between MS and HB vaccination would be of considerable importance

Drug Saf

INTRODUCTION: Hepatitis B (HB) vaccination programs were set up worldwide in the early 1990s. Despite their major focus on reducing the burden of HB infection, they have seldom achieved the targeted population coverage in most countries, including the USA, with around 24.5% of adults being vaccinated against HB. Among proposed reasons for this is the persisting doubt about a possible link between HB vaccination and the occurrence of cases of multiple sclerosis (MS). OBJECTIVE: Our objective was to evaluate a potential safety signal between MS and HB vaccination. We conducted a disproportionality analysis (DPA) using the cases reported to the Vaccine Adverse Event Reporting System (VAERS). METHODS: We calculated the proportional reporting rate (PRR) and reporting odds ratio (ROR) of MS having occurred within the 120 days following HB immunization in adults aged 19-49 years when compared with other vaccines using the reports recorded in the VAERS database. Both ratios were estimated globally and then according to the origin of reports (USA vs. non-USA). We then performed a sensitivity analysis using a broader category of demyelinating events. FINDINGS: MS cases following HB vaccination were more likely to originate from outside the USA and to be reported before 2000 than those associated with other immunizations. All computed ratios were found to be statistically significant, with PRRs ranging from 3.48 to 5.56 and RORs ranging from 3.48 to 5.62. When considering the geographical origin, similar RORs were obtained for both US and non-US cases. CONCLUSION: In VAERS, MS cases were up to five times more likely to be reported after an HB vaccination than after any other vaccination. Since DPA is mainly suited for hypothesis generation, further studies evaluating the nature of the link between MS and HB vaccination would be of considerable importance