Premium
Improved Humoral and Cellular Immune Responses Against the gp120 V3 Loop of HIV‐1 Following Genetic Immunization with a Chimeric DNA Vaccine Encoding the V3 Inserted into the Hepatitis B Surface Antigen
Author(s) -
Anders Fomsgaard,
Nielsen Hv,
Karin Bryder,
Christoffer Tandrup Nielsen,
Roberto Machuca,
Lone Bruun,
Jan Erik Hansen,
Søren Buus
Publication year - 1998
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.1998.00323.x
Subject(s) - virology , immunogenicity , hbsag , v3 loop , epitope , ctl* , biology , dna vaccination , antigen , antibody , immune system , vaccination , hepatitis b virus , immunization , virus , immunology , cd8
The gp120‐derived V3 loop of HIV‐1 is involved in co‐receptor interaction, it guides cell tropism, and contains an epitope for antibody neutralization. Thus, HIV‐1 V3 is an attractive vaccine candidate. The V3 of the MN strain (MN V3) contains both B‐ and T‐cell epitopes, including a known mouse H‐2 d ‐restricted cytotoxic T lymphocyte (CTL) epitope. In an attempt to improve the immunogenicity of V3 in DNA vaccines, a plasmid expressing MN V3 as a fusion protein with the highly immunogenic middle (pre‐S2 + S) surface antigen of hepatitis B virus (HBsAg) was constructed. Epidermal inoculation by gene gun was used for genetic immunization in a mouse model. Antibody and CTL responses to MN V3 and HBsAg were measured and compared with the immune responses obtained after vaccination with plasmids encoding the complete HIV‐1 MN gp160 and HBsAg (pre‐S2 + S), respectively. DNA vaccination with the HIV MN gp160 envelope plasmid induced a slow and low titred anti‐MN V3 antibody response at 12 weeks post‐inoculation (p.i.) and a late appearing (7 weeks), weak and variable CTL response. In contrast, DNA vaccination with the HBsAg‐encoding plasmid induced a rapid and high titred anti‐HBsAg antibody response and a uniform strong anti‐HBs CTL response already 1 week p.i. in all mice. DNA vaccination with the chimeric MN V3/HBsAg plasmid elicited humoral responses against both viruses within 3–6 weeks which peaked at 6–12 weeks and remained stable for at least 25 weeks. In addition, specific CTL responses were induced in all mice against both MN V3 and HBsAg already within the first 3 weeks, lasting at least 11 weeks. Thus, HBsAg acts as a ‘genetic vaccine adjuvant’ augmenting and accelerating the cellular and humoral immune response against the inserted MN V3 loop. Such chimeric HIV–HBsAg plasmid constructs may be useful in DNA immunizations as a ‘carrier’ of protein regions or minimal epitopes which are less exposed or poorly immunogenic.