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Göteborgs universitets publikationer

Induction of long term mucosal immunological memory in humans by an oral inactivated multivalent enterotoxigenic Escherichia coli vaccine

Författare och institution:
Anna Lundgren (Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi); Marianne Jertborn (Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi); Ann-Mari Svennerholm (Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi)
Publicerad i:
Vaccine, 34 ( 27 ) s. 3132-3140
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
We have evaluated the capacity of an oral multivalent enterotoxigenic Escherichia call (ETEC) vaccine (MEV) to induce mucosal immunological memory. MEV consists of four inactivated E. coli strains over expressing the major colonization factors (CFs) CFA/I, CS3, CS5 and CS6 and the LTB-related toxoid LCTBA. Memory responses were analyzed by comparing the magnitudes and kinetics of intestine-derived antibody-secreting cell responses to a single dose of MEV in three groups of adult Swedish volunteers (n = 16-19 subjects per group) in a Phase I trial: non-immunized controls (I) and subjects who in a previous Phase I trial 13-23 months earlier had received two biweekly doses of MEV (II) or MEV + double mutant LT (dmLT) adjuvant (III). Responses against CFs and LTB were analyzed in antibodies in lymphocyte secretions (ALS) of blood mononuclear cells collected before (day 0) and 4/5 and 7 days after immunization. Specific circulating memory B cells present at the time of the single dose vaccination were also studied to determine if such cells may reflect mucosal memory. Considerably higher and significantly more frequent IgA ALS responses against all CFs and LTB were induced by the single vaccine dose in the previously immunized than in non-immunized volunteers. Furthermore, peak IgA ALS responses against all antigens were observed on days 4/5 in most of the previously immunized subjects whereas only a few previously non-vaccinated individuals responded before day 7. Priming with adjuvant did not influence memory responses. Circulating vaccine specific IgA memory B cells were not detected, whereas anti-toxin IgG memory B cells were identified 13-23 months after priming vaccination. We conclude that MEV induces functional mucosal immunological memory which remains at least 1-2 years. Furthermore, our results support that analysis of antibody-secreting cell responses after booster vaccination may be a useful approach to evaluate longstanding mucosal immunological memory in humans. Clinical trials registration: ISRCTN27096290.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Klinisk medicin
ETEC, Oral vaccine, Immunological memory, Mucosal immunity, IgA, b-subunit vaccine, intestinal immune-responses, antibody-secreting cell, cholerae o1 infection, colonization factors, bangladeshi adults, dmlt, adjuvant, etec vaccine, double-blind, phase-i, Immunology, Research & Experimental Medicine
Postens nummer:
Posten skapad:
2016-07-25 16:54

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