Boosting of HIV-1 neutralizing antibody responses by a distally related retroviral envelope protein.

Uchtenhagen H, Schiffner T, Bowles E, Heyndrickx L, LaBranche C, Applequist SE, Jansson M, De Silva T, Back JW, Achour A, Scarlatti G, Fomsgaard A, Montefiori D, Stewart-Jones G, Spetz AL

J. Immunol. 192 (12) 5802-5812 [2014-06-15; online 2014-05-14]

Our knowledge of the binding sites for neutralizing Abs (NAb) that recognize a broad range of HIV-1 strains (bNAb) has substantially increased in recent years. However, gaps remain in our understanding of how to focus B cell responses to vulnerable conserved sites within the HIV-1 envelope glycoprotein (Env). In this article, we report an immunization strategy composed of a trivalent HIV-1 (clade B envs) DNA prime, followed by a SIVmac239 gp140 Env protein boost that aimed to focus the immune response to structurally conserved parts of the HIV-1 and simian immunodeficiency virus (SIV) Envs. Heterologous NAb titers, primarily to tier 1 HIV-1 isolates, elicited during the trivalent HIV-1 env prime, were significantly increased by the SIVmac239 gp140 protein boost in rabbits. Epitope mapping of Ab-binding reactivity revealed preferential recognition of the C1, C2, V2, V3, and V5 regions. These results provide a proof of concept that a distally related retroviral SIV Env protein boost can increase pre-existing NAb responses against HIV-1.

Affiliated researcher

PubMed 24829409

DOI 10.4049/jimmunol.1301898

Crossref 10.4049/jimmunol.1301898

pii: jimmunol.1301898
pmc: PMC4112278
mid: NIHMS585099
GENBANK: KJ579955