Andy DeLaitsch
@delaitsch.bsky.social
antibodies, viruses, cryo-EM -- habitually curious -- BMB graduate student at Caltech
Huge thanks to Florian Klein's lab for this excellent collaboration and to the various lab members who provided so much help seeing this through!
October 6, 2025 at 8:43 PM
Huge thanks to Florian Klein's lab for this excellent collaboration and to the various lab members who provided so much help seeing this through!
All these antibodies exhibit canonical gp120 interactions made by CD4 and CD4bs bNAbs. Interestingly, the VH1-2-encoded N58 is mutated to K58 in the best of these bNAbs, which mimics interactions made between K35 of CD4 and gp120. www.nature.com/articles/s41...
Profiling of HIV-1 elite neutralizer cohort reveals a CD4bs bnAb for HIV-1 prevention and therapy - Nature Immunology
Klein and colleagues characterize 04_A06, a new VH1-2-encoded broadly neutralizing antibody that has marked breadth and potency against extended multiclade HIV-1 pseudovirus panels and can maintain full viral suppression in HIV-1-infected humanized mice.
www.nature.com
October 6, 2025 at 8:32 PM
All these antibodies exhibit canonical gp120 interactions made by CD4 and CD4bs bNAbs. Interestingly, the VH1-2-encoded N58 is mutated to K58 in the best of these bNAbs, which mimics interactions made between K35 of CD4 and gp120. www.nature.com/articles/s41...
The third bNAb, 05_B08, does not have any insertions and does not contact the adjacent gp120. This antibody, exhibited just over 50% breadth, which is much lower than the others.
October 6, 2025 at 8:32 PM
The third bNAb, 05_B08, does not have any insertions and does not contact the adjacent gp120. This antibody, exhibited just over 50% breadth, which is much lower than the others.
Another of the bNAbs, 01_D03, has two separate insertions and a 20-residue long CDRH3, which together allow it to contact conserved residues on the adjacent gp120. This antibody has a 4-residue long FWRH3 insertion in the same location as a 4-residue insertion in 3BNC60/3BNC117.
October 6, 2025 at 8:32 PM
Another of the bNAbs, 01_D03, has two separate insertions and a 20-residue long CDRH3, which together allow it to contact conserved residues on the adjacent gp120. This antibody has a 4-residue long FWRH3 insertion in the same location as a 4-residue insertion in 3BNC60/3BNC117.
Interestingly, a crystal structure of this antibody alone revealed this protruding loop was pre-organized for binding, which is expected to lower the entropic cost for binding.
October 6, 2025 at 8:32 PM
Interestingly, a crystal structure of this antibody alone revealed this protruding loop was pre-organized for binding, which is expected to lower the entropic cost for binding.
These bNAbs differ in the length and position of insertions. The best-in-class bNAb, 04_A06, has an 11-residue long FWRH1 insertion which manifests in a long CDRH1 that reaches over to contact highly conserved residues on the adjacent gp120.
October 6, 2025 at 8:32 PM
These bNAbs differ in the length and position of insertions. The best-in-class bNAb, 04_A06, has an 11-residue long FWRH1 insertion which manifests in a long CDRH1 that reaches over to contact highly conserved residues on the adjacent gp120.
I second this bet.
And then Shankar Balasubramanian for chemistry.
And then Shankar Balasubramanian for chemistry.
October 4, 2025 at 1:58 PM
I second this bet.
And then Shankar Balasubramanian for chemistry.
And then Shankar Balasubramanian for chemistry.
“On Being The Right Size” is a true classic, highly recommend! www.phys.ufl.edu/courses/phy3...
www.phys.ufl.edu
July 28, 2025 at 2:29 PM
“On Being The Right Size” is a true classic, highly recommend! www.phys.ufl.edu/courses/phy3...
Cool demo! Also, it’s nice to see your IgG binds bivalently!
April 15, 2025 at 6:18 PM
Cool demo! Also, it’s nice to see your IgG binds bivalently!
For those interested: iubemcenter.indiana.edu/doc/ruska/ru...
iubemcenter.indiana.edu
December 10, 2024 at 5:28 AM
For those interested: iubemcenter.indiana.edu/doc/ruska/ru...