Protective mucosal immunity elicited by targeted lymph node immunization with a subunit SIV envelope and core vaccine in macaques.
Prevention of sexually transmitted HIV infection was first investigated in non-human primates by mucosal immunization via the rectal, vaginal or male urethral route. This was compared with subcutaneous targeted iliac lymph node (TILN) and systemic intramuscular immunization in non-human primates. TILN immunization elicited the most consistent mucosal sIgA and IgG antibody response in the rectum, vagina, urine and seminal fluid, as well as in blood. Both mucosal and TILN immunization induced a specific CD4+ T cell proliferative response in the iliac lymph nodes which drain these mucosal surfaces, and in the splenic and circulating T cells. In the next experiment macaques were immunized by the TILN route with SIV gp120 and p27 in alum. Rectal mucosal challenge with SIVmac 32H J5 molecular clone (or cell-free virus) induced total protection in four out of seven macaques, compared with infection in 13 of 14 unimmunized macaques or immunized by other routes (p = 0.025). The remaining three macaques immunized by the TILN route showed either decrease in viral load (> 90%) or transient viraemia, indicating that all seven TILN immunized macaques showed total or partial protection of rectal transmission by SIV (p = 0.001). Protection was associated with significant increase in the iliac lymph nodes IgA antibody secreting cells to p27 (p < 0.02), CD8-suppressor factor inhibiting replication of SIV in CD4+ T cells (p < 0.01) and the chemokines RANTES and MIP-1 beta (p < 0.01). We suggest that administration of gp120 and p27 by the TILN route may elicit protective B and T cell immunity which can significantly prevent rectal transmission of SIV or HIV.
Lehner
T
T
Department of Immunology, United Medical School of Guy's Hospital, London, UK.
Wang
Y
Y
Cranage
M
M
Bergmeier
L A
LA
Mitchell
E
E
Tao
L
L
Hall
G
G
Dennis
M
M
Cook
N
N
Jones
I
I
Doyle
C
C
D000818:Animals; D018925:Chemokines / Q000378:metabolism; D015683:Gene Products, gag / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D018928:Immunity, Mucosal; D007114:Immunization / Q000379:methods; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology*; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D008297:Male; D008562:Membrane Glycoproteins; D012007:Rectum; D018449:SAIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D013491:Suppressor Factors, Immunologic / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014759:Viral Envelope Proteins
D018925:Chemokines; C066594:Gag protein p27, Simian immunodeficiency virus; D015683:Gene Products, gag; D015699:HIV Envelope Protein gp120; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D018449:SAIDS Vaccines; D013491:Suppressor Factors, Immunologic; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus