Engineered Bispecific Antibodies with Exquisite HIV-1-Neutralizing Activity.
While the search for an efficacious HIV-1 vaccine remains elusive, emergence of a new generation of virus-neutralizing monoclonal antibodies (mAbs) has re-ignited the field of passive immunization for HIV-1 prevention. However, the plasticity of HIV-1 demands additional improvements to these mAbs to better ensure their clinical utility. Here, we report engineered bispecific antibodies that are the most potent and broad HIV-neutralizing antibodies to date. One bispecific antibody, 10E8V2.0/iMab, neutralized 118 HIV-1 pseudotyped viruses tested with a mean 50% inhibitory concentration (IC50) of 0.002 μg/mL. 10E8V2.0/iMab also potently neutralized 99% of viruses in a second panel of 200 HIV-1 isolates belonging to clade C, the dominant subtype accounting for ∼50% of new infections worldwide. Importantly, 10E8V2.0/iMab reduced virus load substantially in HIV-1-infected humanized mice and also provided complete protection when administered prior to virus challenge. These bispecific antibodies hold promise as novel prophylactic and/or therapeutic agents in the fight against HIV-1.
Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
Yaoxing
Y
Huang
Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
Jian
J
Yu
Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
Anastasia
A
Lanzi
Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
Xin
X
Yao
Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
Chasity D
CD
Andrews
Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
Lily
L
Tsai
Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
Mili R
MR
Gajjar
Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
Ming
M
Sun
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Michael S
MS
Seaman
Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
Neal N
NN
Padte
Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA. Electronic address: dho@adarc.org.
David D
DD
Ho
D000818:Animals; D018033:Antibodies, Bispecific / Q000737:chemistry / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000737:chemistry; D057134:Antibodies, Neutralizing / Q000737:chemistry / Q000276:immunology*; D019302:HIV Envelope Protein gp160 / Q000737:chemistry / Q000276:immunology*; D015658:HIV Infections / Q000517:prevention & control / Q000628:therapy; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007116:Immunization, Passive; D051379:Mice
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D019302:HIV Envelope Protein gp160