Immunogenicity of virosomal adjuvanted trivalent influenza vaccination in allogeneic stem cell transplant recipients.

BACKGROUND: Influenza vaccination is generally recommended to hematopoietic stem cell transplant (HSCT) recipients. However, the seasonal subunit vaccination response is frequently suboptimal, and alternate more efficient vaccination systems must be examined. We compared the immunogenicity of an adjuvanted virosomal influenza and subunit vaccine in HSCT recipients. METHODS: The immunogenicity after a single dose (0.5 mL) of adjuvanted trivalent virosomal vaccination was evaluated in a study cohort of 21 HSCT recipients and compared to a control cohort of 30 HSCT recipients who received a single dose (0.5 mL) of non-adjuvanted seasonal trivalent subunit vaccination over 4 seasons from 2010 to 2014. Whole blood interferon-gamma (IFN-γ) release assays were tested, both before and 30 days after vaccination, in response to influenza pandemic (pdm) H1N1, H3N2, and B antigens. HLA-A*02 dextramers, to gauge for the absolute number of antigen-specific CD8(+) T-cells, and pdm 2009 hemagglutinin inhibition (HI) assays, to test for neutralizing antibodies, were used as immunological readouts. RESULTS: The pdm HI titers were poor in both cohorts with only 23% (5/21) after virosomal vaccination and 13.3% (4/30) in the seasonal vaccine cohort having protective titers (≥40). The delta change of IFN-γ production in response to influenza pdm H1N1 (P = 0.005) and influenza B antigens (P = 0.01) were significantly elevated in blood from individuals who received the virosomal as compared to the seasonal vaccine. The IFN-γ response to pdm H1N1 was stronger (P < 0.001), as compared to seasonal vaccination, in patients vaccinated >6 month post HSCT. We detected a significant increase in the frequency of matrix 1 (GILGFVTL) dextramer-specific CD8(+) T-cells after the virosomal vaccine (P = 0.01). No differences were seen in the hemagglutinin-specific CD8(+) T-cells between the 2 cohorts. CONCLUSION: Vaccination using a virosomal delivery system is beneficial in eliciting robust cellular immune responses to pdm H1N1 influenza in SCT recipients.

Evaluation of pretransplant influenza vaccination in hematopoietic SCT: a randomized prospective study.

Pretransplant influenza vaccination of the donor or allogeneic hematopoietic SCT (HSCT) candidate was evaluated in a randomized study. One hundred and twenty-two HSCT recipients and their donors were assigned to three randomization groups: no pretransplant vaccination (n=38), donor pretransplant vaccination (n=44) or recipient pretransplant vaccination (n=40). Specific IgG was assessed by both hemagglutinin inhibition (HI) and, in 57 patients, by an indirect influenza-specific ELISA at specified times after HSCT. Vaccinated donors had seroprotective HI titers for Ags H1 and H3 (P<0.001) compared with the other groups at the time of donation. The titers against H1 (P=0.028) and H3 (P<0.001) were highest in the pretransplant recipient vaccination group until day 180 after transplantation. A significant difference was found in the specific Ig levels against pandemic H1N1 at 6 months after SCT (P=0.02). The mean IgG levels against pandemic H1N1 and generic H1N1 and H3N2 were highest in the pretransplant recipient vaccination group. We conclude that pretransplant recipient vaccination improved the influenza-specific seroprotection rates.

Increased ß-haemolytic group A streptococcal M6 serotype and streptodornase B-specific cellular immune responses in Swedish narcolepsy cases.

BACKGROUND: Type 1 narcolepsy is a neurological disorder characterized by excessive daytime sleepiness and cataplexy associated with the HLA allele DQB1*06:02. Genetic predisposition along with external triggering factors may drive autoimmune responses, ultimately leading to the selective loss of hypocretin-positive neurons. OBJECTIVE: The aim of this study was to investigate potential aetiological factors in Swedish cases of postvaccination (Pandemrix) narcolepsy defined by interferon-gamma (IFNγ) production from immune cells in response to molecularly defined targets. METHODS: Cellular reactivity defined by IFNγ production was examined in blood from 38 (HLA-DQB1*06:02(+) ) Pandemrix-vaccinated narcolepsy cases and 76 (23 HLA-DQB1*06:02(+) and 53 HLA-DQB1*06:02(-) ) control subjects, matched for age, sex and exposure, using a variety of different antigens: ß-haemolytic group A streptococcal (GAS) antigens (M5, M6 and streptodornase B), influenza (the pandemic A/H1N1/California/7/09 NYMC X-179A and A/H1N1/California/7/09 NYMC X-181 vaccine antigens, previous Flu-A and -B vaccine targets, A/H1N1/Brisbane/59/2007, A/H1N1/Solomon Islands/3/2006, A/H3N2/Uruguay/716/2007, A/H3N2/Wisconsin/67/2005, A/H5N1/Vietnam/1203/2004 and B/Malaysia/2506/2004), noninfluenza viral targets (CMVpp65, EBNA-1 and EBNA-3) and auto-antigens (hypocretin peptide, Tribbles homolog 2 peptide cocktail and extract from rat hypothalamus tissue). RESULTS: IFN-γ production was significantly increased in whole blood from narcolepsy cases in response to streptococcus serotype M6 (P = 0.0065) and streptodornase B protein (P = 0.0050). T-cell recognition of M6 and streptodornase B was confirmed at the single-cell level by intracellular cytokine (IL-2, IFNγ, tumour necrosis factor-alpha and IL-17) production after stimulation with synthetic M6 or streptodornase B peptides. Significantly, higher (P = 0.02) titres of serum antistreptolysin O were observed in narcolepsy cases, compared to vaccinated controls. CONCLUSION: ß-haemolytic GAS may be involved in triggering autoimmune responses in patients who developed narcolepsy symptoms after vaccination with Pandemrix in Sweden, characterized by a Streptococcus pyogenes M-type-specific IFN-γ cellular immune response.

Non-T, non-B acute lymphoblastic leukemia (L3) with t(8;22) and two 14q+ chromosomes.

A patient with L3 leukemia is reported whose leukemic cells were characterized cytogenetically by a duplication of the long arm segment 1q25 leads to q42, trisomy for chromosome 7, t(8;22)(q24;q11), and two 14q+ chromosomes. Immunologic marker analysis revealed the leukemic cells to be of the non-T, non-B ("null") type. This observation, when considered in conjunction with a previous report of heterogeneity in cell lineages of L3 leukemias, raises the possibility of some lymphoid neoplasms arising in stem cells.