H5N1 Influenza Vaccine Formulated with AS03A Induces Strong Cross-Reactive and Polyfunctional CD4 T-Cell Responses

Objective Adjuvantation of an H5N1 split-virion influenza vaccine with AS03(A) substantially reduces the antigen dose required to produce a putatively protective humoral response and promotes cross-clade neutralizing responses. We determined the effect of adjuvantation on antibody persistence and B- and T-cell-mediated immune responses. Methods Two vaccinations with a split-virion A/Vietnam/1194/2004 (H5N1, clade 1) vaccine containing 3.75-30 mu g hemagglutinin and formulated with or without adjuvant were administered to groups of 50 volunteers aged 18-60 years. Results Adjuvantation of the vaccine led to better persistence of neutralizing and hemagglutination-inhibiting antibodies and higher frequencies of antigen-specific memory B cells. Cross-reactive and polyfunctional H5N1-specific CD4 T cells were detected at baseline and were amplified by vaccination. Expansion of CD4 T cells was enhanced by adjuvantation. Conclusion Formulation of the H5N1 vaccine with AS03(A) enhances antibody persistence and induces stronger T- and B-cell responses. The cross-clade T-cell immunity indicates that the adjuvanted vaccine primes individuals to respond to either infection and/or subsequent vaccination with strains drifted from the primary vaccine strain

The burden of varicella from a parent's perspective and its societal impact in The Netherlands: an Internet survey

<p>Abstract</p> <p>Background</p> <p>Varicella is a common childhood disease. Only 5% of first varicella-zoster-virus infections occur asymptomatically. Most data on the burden of varicella stem from health service databases. This study aims to provide insight in the burden of varicella from a parent's perspective including cases outside the healthcare system.</p> <p>Methods</p> <p>An internet questionnaire was developed for parents in the Netherlands to report health care resource use and productivity losses during the varicella episode in their child younger than 6 years. 11,367 invitations were sent out to members with children of an internet panel of a market research agency. 4,168 (37%) parents started the questionnaire (response rate), of which 360 (9%) stopped before completion and 1,838 (44%) were out of the target group. In total 1,970 parents completed the questionnaire. The questionnaire provided a symptom list ranging from common symptoms, such as skin vesicles, itching to fits or convulsions. A posteriori, in the analyses, the symptoms 'skin infections', 'fits/convulsions', 'unconsciousness', and 'balance and movement disorders' were labelled as complications. There was no restriction to time since the varicella episode for inclusion in the analyses.</p> <p>Results</p> <p>The 1,970 respondents had in total 2,899 children aged younger than six years, of which 2,564 (88%) children had had varicella. In 62% of the episodes the parent did not seek medical help. In 18% of all episodes symptoms labelled as complications were reported; in 11% of all episodes parents visited a medical doctor (MD) for a complication. Reporting of complications did not differ (X²; p = 0.964) between children with a recent (≤ 12 months ago) or a more distant (> 12 months) history of varicella. Prescription drugs were used in 12% of the children with varicella; OTC drugs in 72%. Parents reported work loss in 17% of the varicella-episodes (23% when MD visit; 14% when no MD-visit) for on average 14 hours, which equals to 2.5 hours of work loss for any given varicella-episode.</p> <p>Conclusions</p> <p>This study shows the full spectrum of varicella-episodes and associated healthcare use, including the large proportion of cases not seeking medical care and the societal impact associated with those cases.</p

T-chronic lymphocytic leukaemia presenting as primary hypogammaglobulinaemia--evidence of a proliferation of T-suppressor cells.

A 63 year old man with late onset hypogammaglobulinaemia is described. Splenectomy, carried out because of marked splenomegaly and pancytopenia, demonstrated marked T lymphocytic infiltration in the splenic red pulp with prominent germinal centres. A persistent peripheral blood and bone marrow lymphocytosis ensued (10 X 10(9)/l and 40% respectively) and this was consistent with T-chronic lymphocytic leukaemia (T-CLL). Over 88% of his blood lymphocytes were E+, OKT3+, OKT8+ and OKT11+; 54% of the T lymphocytes had receptors for IgG (T gamma cells). Functional studies showed that the T lymphocytes of this patient lacked killer and natural killer cell function but they effectively suppressed the differentiation of normal B cells in a PWM stimulated system. It is suggested that the T-CLL in this patient resulted from the proliferation of the T suppressor subset which was responsible for his hypogammaglobulinaemia

Safety of a Two-Dose Regimen of a Combined Measles, Mumps, Rubella and Varicella Live Vaccine Manufactured with Recombinant Human Albumin.

Abstract BACKGROUND: ProQuad - a vaccine containing antigens from M-M-RVAXPRO (measles, mumps and rubella vaccine) and VARIVAX (varicella vaccine) - is indicated for simultaneous vaccination against measles, mumps, rubella and varicella (MMRV) in individuals from 12 months of age. To eliminate blood-derived products of human origin from the manufacturing process of the MMRV vaccine, recombinant human albumin (rHA) was selected as a replacement for human serum albumin (HSA). METHODS: This open-label, multicentre clinical trial (clinicaltrials.gov identifier NCT00560755) was designed to describe the safety profile of a two-dose schedule of the MMRV vaccine at a 1-month interval in healthy children aged 12-22 months. RESULTS: In total, 3,388 children received at least one dose of the MMRV vaccine. Overall, 3,376 (99.65%) children were included in the post-Dose 1 safety analysis, and 3,342 (98.64%) in the post-Dose 2 safety analysis. After Doses 1 and 2, the frequencies of children experiencing solicited injection-site reactions (Post-Dose 1: erythema 14.31%; swelling 5.57%; pain 10.31%; Post-Dose 2: erythema 30.46%; swelling 13.23%; pain 11.49%), rashes of interest (Post-Dose 1: 11.4%; Post-Dose 2: 2.78%), vaccine-related non-serious systemic adverse events (Post-Dose 1: 34.86; Post-Dose 2: 13.4%) and temperature ≥39.4°C (Post-Dose 1: 25.24%; Post-Dose 2: 12.06%) were consistent with those observed in previous studies of the MMRV vaccine manufactured with HSA. Neither serious allergic-type adverse events nor anaphylactic reactions were reported. CONCLUSION: The results confirm the good safety profiles of MMRV and of MMR vaccines manufactured with rHA