DNA VECTOR CONSTRUCTS THAT PRIME HEPATITIS-B SURFACE ANTIGEN-SPECIFICCYTOTOXIC T-LYMPHOCYTE AND ANTIBODY-RESPONSES IN MICE AFTER INTRAMUSCULAR INJECTION
W. Bohm et al., DNA VECTOR CONSTRUCTS THAT PRIME HEPATITIS-B SURFACE ANTIGEN-SPECIFICCYTOTOXIC T-LYMPHOCYTE AND ANTIBODY-RESPONSES IN MICE AFTER INTRAMUSCULAR INJECTION, Journal of immunological methods, 193(1), 1996, pp. 29-40
We tested the efficiency of induction of immune responses to the small
hepatitis B surface antigen (HBsAg) in mice by intramuscular DNA immu
nization using different vector constructs that allow high levels of H
BsAg expression in mouse cells. The HBsAg-specific responses of class
I-restricted cytotoxic T lymphocytes (CTL) and of B cells (serum antib
ody titers) were measured. Following the intramuscular inoculation of
'naked' DNA, five different vector constructs of 4-8 kb, that containe
d or did not contain an intron and/or the neo gene, in which HBsAg exp
ression was driven by promoter sequences derived from the immediate ea
rly region of HCMV, the SV40 enhancer/promoter region, or a retroviral
3' LTR efficiently primed responses of class I-restricted CD8(+) CTL
precursors. In contrast, the constructs in which HBsAg expression was
driven by HCMV-derived promoter sequences stimulated significantly hig
her levels of HBsAg-specific serum antibody titers after intramuscular
DNA injection than the SV40 or MPSV vector constructs. Large (15 kb)
episomal vector constructs did not stimulate CTL or antibody responses
, The data demonstrate that: (i) intramuscular DNA immunization repres
ents an efficient technique for priming CTL and antibody responses to
HBsAg; (ii) many vectors can be constructed that express an immunogeni
c product after intramuscular inoculation of 'naked' DNA; (iii) the ef
ficiency of the tested vector constructs to prime after DNA immunizati
on, either a CTL response, or an antibody response, differs.