Dataset Information

Targeting the N332-supersite of the HIV-1 envelope for vaccine design.

ABSTRACT: Introduction: Broadly neutralizing antibodies (bNAbs) that are able to target diverse global viruses are widely believed to be crucial for an HIV-1 vaccine. Several conserved targets recognized by these antibodies have been identified on the HIV-1 envelope glycoprotein. One such target that shows particular promise for vaccination is the N332-supersite.Areas covered: This review describes the potential of the N332-supersite epitope as an immunogen design platform. We discuss the structure of the epitope and the bNAbs that target it, emphasizing their diverse modes of binding. Furthermore, the successes and limitations of recent N332-supersite immunization studies are discussed.Expert opinion: During HIV-1 infection, some of the broadest and most potent bNAbs target the N332-supersite. Furthermore, some of these antibodies require less affinity maturation than the high levels typical of many bNAbs, making these potentially more achievable vaccine targets. In addition, bNAbs bind this epitope with multiple angles of approach and glycan dependencies, perhaps increasing the probability of eliciting such responses by vaccination. Animal studies have shown that N332-supersite bNAb precursors can be activated by novel immunogens. While follow-up studies must establish whether boosting strategies can drive the maturation of bNAbs from these precursors, the development of targeted N332-supersite immunogens expands our arsenal of potential HIV-1 vaccine candidates.

SUBMITTER: Moyo T

PROVIDER: S-EPMC7530370 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:IntroductionThe development of a human immunodeficiency virus 1 (HIV-1) vaccine remains a formidable challenge. An effective vaccine likely requires the induction of broadly neutralizing antibodies (bNAbs), which likely involves the use of native-like HIV-1 envelope (Env) trimers at some or all stages of vaccination. Development of such trimers has been very difficult, but much progress has been made in the past decade, starting with the BG505 SOSIP trimer, elucidation of its atomic structure and implementing subsequent design iterations. This progress facilitated understanding the weaknesses of the Env trimer, fuelled structure-guided HIV-1 vaccine design and assisted in the development of new vaccine designs. This review summarizes the relevant literature focusing on studies using structural biology to reveal and define HIV-1 Env sites of vulnerability; to improve Env trimers, by creating more stable versions; understanding antibody responses in preclinical vaccination studies at the atomic level; understanding the glycan shield; and to improve "on-target" antibody responses versus "off-target" responses.MethodsThe authors conducted a narrative review of recently published articles that made a major contribution to HIV-1 structural biology and vaccine design efforts between the years 2000 and 2021.DiscussionThe field of structural biology is evolving at an unprecedented pace, where cryo-electron microscopy (cryo-EM) and X-ray crystallography provide complementary information. Resolving protein structures is necessary for defining which Env surfaces are accessible for the immune system and can be targeted by neutralizing antibodies. Recently developed techniques, such as electron microscopy-based polyclonal epitope mapping (EMPEM) are revolutionizing the way we are analysing immune responses and shed light on the immunodominant targets on new vaccine immunogens. Such information accelerates iterative vaccine design; for example, by reducing undesirable off-target responses, while improving immunogens to drive the more desirable on-target responses.ConclusionsResolving high-resolution structures of the HIV-1 Env trimer was instrumental in understanding and improving recombinant HIV-1 Env trimers that mimic the structure of viral HIV-1 Env spikes. Newly emerging techniques in structural biology are aiding vaccine design efforts and improving immunogens. The role of structural biology in HIV-1 vaccine design has indeed become very prominent and is unlikely to diminish any time soon.

Dataset Information

Targeting the N332-supersite of the HIV-1 envelope for vaccine design.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets