Enzymatic removal of mannose moieties can increase the immune response to HIV-1 gp120 in vivo.
The Env glycoproteins gp120 and gp41 are used in humoral immunity-based vaccines against human immunodeficiency virus (HIV-1) infection. One among many obstacles to such a vaccine is the structural defenses of Env glycoproteins that limit their immunogenicity. For example, gp120 mannose residues can induce immunosuppressive responses in vitro, including IL-10 expression, via mannose C-type lectin receptors on antigen-presenting cells. Here, we have investigated whether mannose removal alters gp120 immunogenicity in mice. Administering demannosylated gp120 (D-gp120) in the T(H)2-skewing adjuvant Alum induced approximately 50-fold higher titers of anti-gp120 IgG, compared to unmodified gp120. While the IgG subclass profile was predominantly T(H)2-associated IgG1, Abs of the T(H)1-associated IgG2a and IgG3 subclasses were also detectable in D-gp120 recipients. Immunizing with D-gp120 also improved T-cell responses. Giving an IL-10 receptor blocking MAb together with unmodified gp120 in Alum increased the anti-gp120 IgG titer, implicating IL-10 as a possible mediator of auto-suppressive responses to gp120.
Banerjee
Kaustuv
K
Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, USA.
Andjelic
Sofija
S
Klasse
Per Johan
PJ
Kang
Yun
Y
Sanders
Rogier W
RW
Michael
Elizabeth
E
Durso
Robert J
RJ
Ketas
Thomas J
TJ
Olson
William C
WC
Moore
John P
JP
D016915:AIDS Vaccines / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D008358:Mannose / Q000378:metabolism*; D008361:Mannosidases / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D053701:Receptors, Interleukin-10 / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G; D053701:Receptors, Interleukin-10; D016753:Interleukin-10; D008361:Mannosidases; D008358:Mannose