Mucosal AIDS vaccine reduces disease and viral load in gut reservoir and blood after mucosal infection of macaques.
Given the mucosal transmission of HIV-1, we compared whether a mucosal vaccine could induce mucosal cytotoxic T lymphocytes (CTLs) and protect rhesus macaques against mucosal infection with simian/human immunodeficiency virus (SHIV) more effectively than the same vaccine given subcutaneously. Here we show that mucosal CTLs specific for simian immunodeficiency virus can be induced by intrarectal immunization of macaques with a synthetic-peptide vaccine incorporating the LT(R192G) adjuvant. This response correlated with the level of T-helper response. After intrarectal challenge with pathogenic SHIV-Ku2, viral titers were eliminated more completely (to undetectable levels) both in blood and intestine, a major reservoir for virus replication, in intrarectally immunized animals than in subcutaneously immunized or control macaques. Moreover, CD4+ T cells were better preserved. Thus, induction of CTLs in the intestinal mucosa, a key site of virus replication, with a mucosal AIDS vaccine ameliorates infection by SHIV in non-human primates.
Belyakov
I M
IM
Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, Bethesda, Maryland, USA. belyakov@box-b.nih.gov
Hel
Z
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Kelsall
B
B
Kuznetsov
V A
VA
Ahlers
J D
JD
Nacsa
J
J
Watkins
D I
DI
Allen
T M
TM
Sette
A
A
Altman
J
J
Woodward
R
R
Markham
P D
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Clements
J D
JD
Franchini
G
G
Strober
W
W
Berzofsky
J A
JA
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000163:Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D000285:Administration, Rectal; D000595:Amino Acid Sequence; D000818:Animals; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D015684:Gene Products, pol / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000821:virology*; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D012007:Rectum / Q000821:virology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D013602:T-Lymphocytes, Cytotoxic; D006377:T-Lymphocytes, Helper-Inducer; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000627:therapeutic use; D019562:Viral Load
D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; C066594:Gag protein p27, Simian immunodeficiency virus; D015683:Gene Products, gag; D015684:Gene Products, pol; D015395:Histocompatibility Antigens Class I; C110764:Mamu-A 01 antigen; D014614:Vaccines, Synthetic