Effects of various adjuvants and a viral infection on the antibody specificity toward native or cryptic epitopes of a protein antigen

K A GÓMEZ; S A LONGHI; V J MARINO; P A MATHIEU; M E LOUREIRO; J-P COUTELIER; L P ROGUIN; L A RETEGUI

SCANDINAVIAN JOURNAL OF IMMUNOLOGY

Blackwell Publishing Ltd.

Año: 2003 vol. 57 p. 144 - 150

0300-9475

An immunization protocol that induces antibodies (Abs) directed to cryptic epitopes of a protein antigen (Ag) reduces the efficacy of vaccines that ideally should induce Abs against native epitopes. We have shown earlier that viral infections concomitant with immunization against a protein tend to shift the specificity toward cryptic epitopes and tend to induce the production auto-antibodies (autoAbs). Here, we show the effectos of three adjuvants on the Ab specificity in the absence or presence of a viral infecton (lactate dehydrogenase elevating virus or LDV) with human growth hormone (hGH) being, as before, the protein Ag.Pathogen-free CBA-Ht and BALB/c mice were immunized with hGH in the presence of complete Freund's adjuvant (CFA), monophosphoryl lipid A (MPL) or alum, with the animals being either infected with LDV or not infected with LDV. Conventional and competition enzyme-linked immunosorbent assays (ELISAs) indicated that in non infected mice, CFA induced higher titres of anti-hGH Ab that did MPL or alum, with the Ab being almost totally directed to cryptic hGH epitopes. Strikingly, CFA plus LDV infection in CBA/Ht mice shifted the specificity of the anti-hGH Ab toward native epitopes, whereas the virus decreased the Ab titre when MPL or alum was used. Western blot results showed that 70% of mice immunized with hGH in the presence of any adjuvant produced autoAbs against a variety of tissue Ags. The amount of autoAb and the concentration of Abs to hGH cryptic epitopes did correlate, suggestin a relationship between both kind of Ab. Significant differences were observed in the various effects of adjuvants and the viral infection between the two mouse strains used in this work.