Generation of human anti-HIV-1 ENV monoclonal antibodies with neutralizing activity from humanized mice infected with HIV-1

A method of producing human antibodies or antibody fragments thereof comprising the steps of:

• a) administering a virus or virus-like particle to a non-human mammal comprising heterologous human immune cells, wherein the virus or virus-like particle comprises a nucleotide sequence encoding an HIV-1 env gene as set forth in SEQ ID NO:15, and wherein the non-human mammal is a transgenic mouse that lacks mature lymphocytes and natural killer (NK) cells and comprises one or more engrafted human tissues selected from the group consisting of human fetal thymus tissue, human fetal liver tissue, and human CD34+ fetal liver cells;
• and
• b) isolating a population of mammalian immunoglobulin-producing cells from the non-human mammal, thereby producing the human antibodies or antibody fragments thereof, wherein the human antibodies are anti-HIV-1 antibodies.