Perspective

A critical question for HIV vaccine development: Which antibodies to induce?

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Science  11 Jul 2014:
Vol. 345, Issue 6193, pp. 167-168
DOI: 10.1126/science.1256526

Tables

  • Table 1 Comparison of conventional and exceptional broadly neutralizing antibodies.

    CharacteristicsConventional antibodiesExceptional broadly neutralizing antibodies
    Neutralizing potency in vitro
    Tier 1 pseudoviruses
    <0.02 to >50 ug/ml (57)
    <0.04 to 26 ug/ml (58)
    <<1 ug/ml
    Tier 2 pseudoviruses0.6 to >50 ug/ml (57)
    15 to >50 ug/ml (58)
    0.02 to 27 ug/ml (6264)
    Percentage VH chain somatic hypermutation from germline1 to 12% (59, 60)17 to 48% (16, 62, 65)
    Breadth of neutralization
    Tier 1 pseudoviruses
    29 to 42% (57);
    50 to 90% (26);
    7 to 50% (58)
    100%
    Tier 2 pseudoviruses1 to 4% (57)
    0 to 9% (58)
    72 to 100% (62, 6567)
    Vaccine strategy requiredPrime (ALVAC) + Boost (gp120) (43)
    Prime (DNA or pox vector) + Boost (gp120 protein) or recombinant protein alone (61)
    Prime (DNA) + Boost (epitope-scaffold protein immunogen) (20)
    Starting with a bnAb, infer the full antibody lineage, including the unmutated ancestor and early intermediates and use their sequences as templates for the design of HIV-1 immunogens with high-affinity binding to design sequential immunogens to guide the Ab response to produce bnAbs.
    Prevalence in infectionPresent in virtually all infected individuals1 to 25% (13)
    Time needed to evolveWeeks to months (41, 42)Months to years (11, 12)

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