HIV-1 vaccine
A method for inducing an immune response against HIV in a subject includes the step of preparing an HIV-1 gp120 envelope protein coding sequence particle having an N425K mutation, introducing the HIV-1 gp120 protein coding sequence particle having an N425K mutation into an expression construct using yeast homologous recombination, transfecting a cell with the expression construct, wherein the HIV-1 particle is secreted by the cell, and administering the secreted HIV-1 particle and a pharmaceutically acceptable carrier to the subject, wherein the secreted HIV-1 particle stimulates an immune response in the subject.
1. A vaccine for HIV-1 comprising:
a vector, the vector including an HIV-1 backbone coding sequence;
a replication defective polynucleotide encoding a gp120 HIV-1 envelope protein having an N425K mutation, based on HBX2 reference virus numbering, wherein the gp120 HIV-1 envelope protein having an N425K mutation binds to CD4; and
a pharmaceutically acceptable carrier.
2. The vaccine of claim 1 , wherein the gp120 HIV-1 envelope protein including an N425K mutation induces an immune response to HIV-1 when administered to a subject.
3. The vaccine of claim 2 , the immune response comprising the generation of broadly neutralizing induced CD4 (CD4i) HIV-1 antibodies directed to a CD4 coreceptor binding site of HIV-1.
4. The vaccine of claim 1 , the vector comprising a NL4-3 backbone HIV-1 vector.
5. The vaccine of claim 1 , the vector comprising a SHIV vector.
6. The vaccine of claim 1 , wherein the replication defective polynucleotide encoding a gp120 HIV-1 envelope protein having an N425K mutation is prepared from an HIV-1 virus having the mutation.
7. A method of producing broadly neutralizing CD4i HIV-1 antibodies in a host subject, the method comprising:
administering to the host subject a vaccine for HIV-1, the vaccine including a vector, the vector including an HIV-1 backbone coding sequence and a replication defective polynucleotide encoding a gp120 HIV-1 envelope protein having an N425K mutation, wherein the gp120 HIV-1 envelope protein having an N425K mutation binds to CD4, and a pharmaceutically acceptable carrier;
obtaining a biological sample from the host subject, the sample including broadly neutralizing CD4i antibodies directed to a CD4 coreceptor biding site of HIV-1 generated by the host in response to the vaccine; and
isolating the broadly neutralizing CD4i antibodies from the sample.
8. The method of claim 7 , wherein the host subject is a CD4 human CD4+B cell transgenic mouse.
9. The method of claim 7 , the biological sample comprising a blood sample.