Vaccination with different group 2 influenza subtypes alters epitope targeting and breadth of hemagglutinin stem-specific human B cells.

The conserved influenza hemagglutinin stem, which is a target of cross-neutralizing antibodies, is now used in vaccine strategies focused on protecting against influenza pandemics. Antibody responses to group 1 stem have been extensively characterized, but little is known about group 2. Here, we characterized the stem-specific repertoire of individuals vaccinated with one of three group 2 influenza subtypes (H3, H7, or H10).

A multidonor class of highly glycan-dependent HIV-1 gp120-gp41 interface-targeting broadly neutralizing antibodies.

Antibodies that target the gp120-gp41 interface of the HIV-1 envelope (Env) trimer comprise a commonly elicited category of broadly neutralizing antibodies (bNAbs). Here, we isolate and characterize VRC44, a bNAb lineage with up to 52% neutralization breadth. The cryoelectron microscopy (cryo-EM) structure of antibody VRC44.

HIV-1-envelope trimer transitions from prefusion-closed to CD4-bound-open conformations through an occluded-intermediate state.

HIV-1 infection is initiated by the interaction between the gp120 subunit in the envelope (Env) trimer and the cellular receptor CD4 on host cells. This interaction induces substantial structural rearrangement of the Env trimer. Currently, static structural information for prefusion-closed trimers, CD4-bound prefusion-open trimers, and various antibody-bound trimers is available.

Vaccine-elicited and naturally elicited antibodies differ in their recognition of the HIV-1 fusion peptide.

Broadly neutralizing antibodies have been proposed as templates for HIV-1 vaccine design, but it has been unclear how similar vaccine-elicited antibodies are to their naturally elicited templates. To provide insight, here we compare the recognition of naturally elicited and vaccine-elicited antibodies targeting the HIV-1 fusion peptide, which comprises envelope (Env) residues 512-526, with the most common sequence being AVGIGAVFLGFLGAA. Naturally elicited antibodies bound peptides with substitutions to negatively charged amino acids at residue positions 517-520 substantially better than the most common sequence, despite these substitutions rarely appearing in HIV-1; by contrast, vaccine-elicited antibodies were less tolerant of sequence variation, with no substitution of residues 512-516 showing increased binding.