Immunogenicity of HIV-1 Env and Gag in baboons using a DNA prime/protein boost regimen.
OBJECTIVE
To evaluate the immunogenicity of sequence-modified HIV env and gag in baboons using DNA prime and protein boost strategy.


METHODS
Synthetic sequence-modified HIV gene cassettes were constructed that expressed three different forms of Env proteins, gp140, gp140mut and gp140TM, plus or minus a mutation in the protease-cleavage site. These plasmids were used to immunize baboons (Papio cynocephalus). A group of baboons was also immunized with both env and gag DNA followed by p55Gag virus-like particles (VLP) boost.


RESULTS
Modest antibody responses and low or no lymphoproliferative responses were observed following multiple DNA immunizations. In contrast, strong antibodies and substantial antigen-specific lymphoproliferative responses were seen following booster immunizations with oligomeric Env protein (o-gp140US4) in MF59. Neutralizing antibody responses were scored against T cell line adapted HIV-1 strains after the protein boosters, but neutralizing responses were low or absent against homologous and heterologous primary isolate strains. In the group receiving both gag and env vaccines, modest antigen-specific antibody and lymphoproliferative responses were scored after the DNA immunizations; these responses were enhanced several-fold upon boosting with the VLP preparations. The addition of Gag antigen did not interfere with Env-specific antibody responses, but there was a negative effect on the levels of Env-specific lymphoproliferation.


CONCLUSIONS
These results highlight the importance of improving the potency of HIV DNA vaccines by enhanced DNA delivery and prime-boost vaccine technologies to generate more robust immune responses in larger animal models. In addition, care must be taken when immunizations with Env and Gag antigens are performed together.
Leung
Louisa
L
Chiron Corp., Emeryville, California 94608, USA.
Srivastava
Indresh K
IK
Kan
Elaine
E
Legg
Harold
H
Sun
Yide
Y
Greer
Catherine
C
Montefiori
David C
DC
zur Megede
Jan
J
Barnett
Susan W
SW
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D000915:Antibody Affinity; D002455:Cell Division / Q000276:immunology; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology*; D015683:Gene Products, gag / Q000276:immunology; D015483:HIV Antibodies / Q000096:biosynthesis; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D007114:Immunization / Q000379:methods; D007117:Immunization, Secondary / Q000379:methods; D016254:Mutagenesis, Insertional; D010215:Papio; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D004279:DNA, Viral; D015686:Gene Products, env; D015683:Gene Products, gag; D015483:HIV Antibodies; D019444:Vaccines, DNA; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1