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Cross-reactivity and avidity of antibody responses induced in humans by the oral inactivated multivalent enterotoxigenic Escherichia coli (ETEC) vaccine ETVAX

Artikel i vetenskaplig tidskrift
Författare Susannah Leach
Anna Lundgren
N. Carlin
Madeleine Löfstrand
Ann-Mari Svennerholm
Publicerad i Vaccine
Volym 35
Nummer/häfte 32
Sidor 3966-3973
ISSN 0264-410X
Publiceringsår 2017
Publicerad vid Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi
Sidor 3966-3973
Språk en
Länkar dx.doi.org/10.1016/j.vaccine.2017.0...
Ämnesord ETEC vaccine, Colonisation factors, Antibodies, Mucosal IgA, Cross-reactivity, Avidity, factor-antigen-i, colonization-factor, immunological memory, immune-responses, bangladeshi children, developing-countries, diarrheal, patients, cell responses, dmlt adjuvant, immunogenicity, Immunology, Research & Experimental Medicine
Ämneskategorier Immunologi

Sammanfattning

We investigated whether the oral inactivated, multivalent enterotoxigenic Escherichia coli (ETEC) vaccine ETVAX, consisting of four E. coli strains over-expressing the colonisation factors (CFs) CFA/I, CS3, CS5 and CS6, combined with the toxoid LCTBA, could induce cross-reactive antibodies to CFs related to the CFA/I and CS5 families. We also evaluated the avidity of vaccine induced antibodies against the toxoid and CFs. Cross-reactivity was analysed in mucosal (faecal and antibodies in lymphocyte supernatants, ALS) samples, and antibody avidity in serum and ALS samples, from two phase I trials: a primary vaccination study, where two oral doses of ETVAX were given the double mutant heat labile toxin (dmLT) adjuvant at a 2-week interval, and a booster vaccination study, where a single booster dose of ETVAX was given 13-23 months after primary vaccinations. We found that 65-90% of subjects who had responded to CFA/I in ALS or faecal specimens also developed cross-reactive antibodies to the related CFs tested, i.e. CS1, CS14 and CS17, and that approximately 80% of those responding to CS5 also responded to the closely related CS7. For subjects who had developed cross-reactive antibodies, the magnitudes of responses against vaccine CFs and related non-vaccine CFs were comparable. Using both a simple method of antibody avidity determination based on limiting antigen dilution, as well as a chaotropic ELISA method, we found that the avidity of serum and ALS antibodies to key vaccine antigens increased after a late booster dose compared to after primary vaccination. Our results suggest that the cross-reactive antibody responses against multiple CFs may result in expanded ETEC strain coverage of ETVAX and that repeated vaccinations induce vaccine-specific antibodies with increased binding capacity.

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