Cross-reactive monoclonal antibodies to multiple HIV-1 subtype and SIVcpz envelope glycoproteins.
The extraordinarily high level of genetic variation of HIV-1 env genes poses a challenge to obtain antibodies that cross-react with multiple subtype Env glycoproteins. To determine if cross-reactive monoclonal antibodies (mAbs) to highly conserved epitopes in HIV-1 envelope glycoproteins can be induced, we immunized mice with wild-type or consensus HIV-1 Env proteins and characterized a panel of ten mAbs that reacted with varying breadth to subtypes A, B, C, D, F, G, CRF01_AE, and a highly divergent SIVcpzUS Env proteins by ELISA and Western blot analysis. Two mAbs (3B3 and 16H3) cross-reacted with all tested Env proteins, including SIVcpzUS Env. Surface plasmon resonance analyses showed both 3B3 and 16H3 bound Env proteins with high affinity. However, neither neutralized primary HIV-1 pseudoviruses. These data indicate that broadly reactive non-neutralizing monoclonal antibodies can be elicited, but that the conserved epitopes that they recognize are not present on functional virion trimers. Nonetheless, such mAbs represent valuable reagents to study the biochemistry and structural biology of Env protein oligomers.
Gao
Feng
F
Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA. fgao@duke.edu
Scearce
Richard M
RM
Alam
S Munir
SM
Hora
Bhavna
B
Xia
Shimao
S
Hohm
Julie E
JE
Parks
Robert J
RJ
Ogburn
Damon F
DF
Tomaras
Georgia D
GD
Park
Emily
E
Lomas
Woodrow E
WE
Maino
Vernon C
VC
Fiscus
Susan A
SA
Cohen
Myron S
MS
Moody
M Anthony
MA
Hahn
Beatrice H
BH
Korber
Bette T
BT
Liao
Hua-Xin
HX
Haynes
Barton F
BF
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification; D000915:Antibody Affinity; D003429:Cross Reactions; D015483:HIV Antibodies / Q000276:immunology* / Q000302:isolation & purification; D015497:HIV-1 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011485:Protein Binding; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D020349:Surface Plasmon Resonance; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus