Skip to main content

What Are the Primary Limitations in B-Cell Affinity Maturation, and How Much Affinity Maturation Can We Drive with Vaccination? Breaking through Immunity's Glass Ceiling.

Publication ,  Journal Article
Kelsoe, G; Haynes, BF
Published in: Cold Spring Harb Perspect Biol
May 1, 2018

A key goal of HIV-1 vaccine development is the induction of broadly neutralizing antibodies (bnAbs) targeted to the vulnerable regions of the HIV envelope. BnAbs develop over time in ∼50% of HIV-1-infected individuals. However, to date, no vaccines have induced bnAbs and few or none of these vaccine-elicited HIV-1 antibodies carry the high frequencies of V(D)J mutations characteristic of bnAbs. Do the high frequencies of mutations characteristic of naturally induced bnAbs represent a fundamental barrier to the induction of bnAbs by vaccines? Recent studies suggest that high frequencies of V(D)J mutations can be achieved by serial vaccination strategies. Rather, it appears that, in the absence of HIV-1 infection, physiologic immune tolerance controls, including a germinal center process termed affinity reversion, may limit vaccine-driven bnAb development by clonal elimination or selecting for mutations incompatible with bnAb activity.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Cold Spring Harb Perspect Biol

DOI

EISSN

1943-0264

Publication Date

May 1, 2018

Volume

10

Issue

5

Location

United States

Related Subject Headings

  • Vaccination
  • Humans
  • HIV-1
  • HIV Antibodies
  • B-Lymphocytes
  • Antigens
  • Antibody Formation
  • Antibody Affinity
  • Antibodies, Neutralizing
  • 3105 Genetics
 

Citation

APA
Chicago
ICMJE
MLA
NLM

Published In

Cold Spring Harb Perspect Biol

DOI

EISSN

1943-0264

Publication Date

May 1, 2018

Volume

10

Issue

5

Location

United States

Related Subject Headings

  • Vaccination
  • Humans
  • HIV-1
  • HIV Antibodies
  • B-Lymphocytes
  • Antigens
  • Antibody Formation
  • Antibody Affinity
  • Antibodies, Neutralizing
  • 3105 Genetics