Multiprotein HIV type 1 clade B DNA/MVA vaccine: construction, safety, and immunogenicity in Macaques.
Recently, a simian/human immunodeficiency virus (SHIV) vaccine consisting of priming with a Gag-Pol-Env-expressing DNA and boosting with a Gag-Pol-Env-expressing recombinant modified vaccinia Ankara (rMVA) has successfully controlled a virulent SHIV challenge in a macaque model. In this, and the accompanying paper, we report on the construction and testing of a Gag-Pol-Env DNA/MVA vaccine for HIV-1/AIDS. The DNA vaccine, pGA2/JS2, expresses aggregates of Gag proteins and includes safety mutations that render it integration, reverse transcription, and packaging defective. The rMVA vaccine, MVA/HIV 48, is integration and reverse transcription defective and has a truncated Env to enhance expression on the plasma membrane. In a study in rhesus macaques, priming with pGA2/JS2 and boosting with MVA/HIV 48 raised high frequencies of T cells for Gag and Env and lower frequencies of T cells for PR, RT, and Tat. Stimulations with five peptide pools for Gag and seven peptide pools for Env revealed epitopes for cellular immune responses throughout Gag and Env. On average, CD4 T cells from the vaccinated animals recognized 7.1 peptide pools and CD8 T cells, 3.2 peptide pools. Both the height and the breadth of the elicited cellular response provide hope that this multiprotein DNA/MVA vaccine will successfully control clade B isolates of HIV-1, as well as contribute to the control of other clades and recombinant forms of HIV-1/AIDS.
Smith
James M
JM
Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia 30329, USA.
Amara
Rama Rao
RR
McClure
Harold M
HM
Patel
Milloni
M
Sharma
Sunita
S
Yi
Hong
H
Chennareddi
Lakshmi
L
Herndon
James G
JG
Butera
Salvatore T
ST
Heneine
Walid
W
Ellenberger
Dennis L
DL
Parekh
Bharat
B
Earl
Patricia L
PL
Wyatt
Linda S
LS
Moss
Bernard
B
Robinson
Harriet L
HL
D016915:AIDS Vaccines / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000032:analysis; D017353:Gene Deletion; D015686:Gene Products, env / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D015752:Genes, env; D015750:Genes, gag; D015751:Genes, pol; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000517:prevention & control; D054303:HIV Reverse Transcriptase / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D007117:Immunization, Secondary; D008253:Macaca mulatta; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D011995:Recombination, Genetic; D015302:Simian Immunodeficiency Virus / Q000235:genetics; D014611:Vaccination; D019444:Vaccines, DNA / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*
D016915:AIDS Vaccines; D016207:Cytokines; D015686:Gene Products, env; D015683:Gene Products, gag; D015483:HIV Antibodies; D019444:Vaccines, DNA; D054303:HIV Reverse Transcriptase