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Recombinant Semliki Forest virus vectors encoding hepatitis B virus small surface and pre‐S1 antigens induce broadly reactive neutralizing antibodies
Author(s) -
NiedreOtomere B.,
Bogdanova A.,
Skrastina D.,
Zajakina A.,
Bruvere R.,
Ose V.,
Gerlich W. H.,
Garoff H.,
Pumpens P.,
Glebe D.,
Kozlovska T.
Publication year - 2012
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/j.1365-2893.2012.01594.x
Subject(s) - virology , semliki forest virus , antibody , antigen , biology , immunogen , hepatitis b virus , neutralizing antibody , virus , epitope , antiserum , gene , immunology , rna , monoclonal antibody , biochemistry
Summary. Most hepatitis B virus (HBV) vaccines consist of viral small surface (S) protein subtype adw2 expressed in yeast cells. In spite of good efficacy, HBV‐genotype and subtype differences, escape mutants and insufficient Th1 activation remain potential problems. To address these problems, we generated recombinant Semliki Forest virus (rSFV) vectors encoding S protein, subtype adw2 or ayw2, or a fragment of the large surface protein, amino acids 1–48 of the pre‐S1 domain, fused to S (pre‐S1.1–48/S). The antigen loop in S protein and the selected pre‐S1 sequences are known targets of neutralizing antibodies. BALB/c mice were immunized intravenously with 10 7 rSFV particles and 10 8 rSFV particles 3 weeks later. Antibodies induced by rSFV encoding S proteins reacted preferentially with subtype determinants of yeast‐derived S antigen but equally well with patient‐derived S antigen. Immunization with rSFV encoding pre‐S1.1–48/S resulted in formation of pre‐S1‐ and S‐specific immunoglobulin G (IgG), while immunization with the isogenic mutant without S start codon induced pre‐S1 antibodies only. Neutralizing antibodies were determined by mixing with plasma‐derived HBV/ayw2 and subsequent inoculation of susceptible primary hepatocyte cultures from Tupaia belangeri. S/adw2 antisera neutralized HBV/ayw2 as effectively as antisera raised with S/ayw2. The pre‐S1 antibodies also completely neutralized HBV infectivity. The IgG1/IgG2a ratios ranged from 0.28 to 0.88 in the four immunized groups and were lowest for the pre‐S1.1–48/S vector, indicating the strongest Th1 response. This vector type may induce subtype‐independent and S‐escape‐resistant neutralizing antibodies against HBV.