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Review
. 2010 Sep;5(5):421-7.
doi: 10.1097/COH.0b013e32833d2d45.

Strategies for eliciting HIV-1 inhibitory antibodies

Georgia D Tomaras  1 , Barton F Haynes
Affiliations
Review

Strategies for eliciting HIV-1 inhibitory antibodies

Georgia D Tomaras et al. Curr Opin HIV AIDS. 2010 Sep.

Abstract

Purpose of review: Major roadblocks persist in the development of vaccines that elicit potent neutralizing antibodies targeting diverse HIV-1 strains, similar to known broadly neutralizing HIV-1 human monoclonal antibodies. Alternatively, other types of anti-HIV-1 envelope antibodies that may not neutralize HIV-1 in traditional neutralization assays but have other anti-HIV-1 activities (hereafter termed HIV-1 inhibitory antibodies) can be elicited by current vaccine strategies, and numerous studies are exploring their roles in preventing HIV-1 acquisition. We review examples of strategies for eliciting potentially protective HIV-1 inhibitory antibodies.

Recent findings: Heterologous prime-boost strategies can yield anti-HIV immune responses, although only one (canarypox prime, Env protein boost) has been tested and shown positive results in an efficacy trial (RV144). Although the immune correlates of protection are as yet undefined, the reduced rate of acquisition without a significant effect on initial viral loads or CD4 T-cell counts, have raised the hypothesis of an RV144 vaccine-elicited transient protective B-cell response.

Summary: In light of the RV144 trial, there is a critical need to define the entire functional spectrum of anti-HIV-1 antibodies, how easily each can be elicited, and how effective different types of antibody effector mechanisms can be in prevention of HIV-1 transmission.

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References

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References and recommended reading

    1. Scheid JF, Mouquet H, Feldhahn N, Seaman MS, Velinzon K, Pietzsch J, Ott RG, Anthony RM, Zebroski H, Hurley A, et al. Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals. Nature. 2009;458:636–640. *A key study that isolated HIV-1 neutralizing antibodies from HIV-1 specific memory B cells using HIV-1 gp140 protein to identify and capture the B cells.

    1. Walker LM, Phogat SK, Chan-Hui PY, Wagner D, Phung P, Goss JL, Wrin T, Simek MD, Fling S, Mitcham JL, et al. Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science. 2009;326:285–289. * A novel study that isolated two broadly neutralizing antibodies that now represent new targets for vaccine design.

    1. Wu X, Yang Z-Y, Li Y, Hogerkorp C-M, Schief WR, Seaman MS, Zhou T, Schmidt SD, Wu L, Xi L, et al. Rational design of envelope surface identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science. 2010 In Press. *An elegant study that identified CD4bs antibodies with extensive neutralization breadth and also provides proof of concept that bNAb to the conserved receptor binding site of Env can be elicited in humans.

    1. Tudor D, Derrien M, Diomede L, Drillet AS, Houimel M, Moog C, Reynes JM, Lopalco L, Bomsel M. HIV-1 gp41-specific monoclonal mucosal IgAs derived from highly exposed but IgG-seronegative individuals block HIV-1 epithelial transcytosis and neutralize CD4(+) cell infection: an IgA gene and functional analysis. Mucosal Immunol. 2009;2:412–426. *An important study that identifies and isolates a potentially protective IgA antibody that was naturally elicited.

    1. Lai SK, Hida K, Shukair S, Wang YY, Figueiredo A, Cone R, Hope TJ, Hanes J. Human immunodeficiency virus type 1 is trapped by acidic but not by neutralized human cervicovaginal mucus. J Virol. 2009;83:11196–11200. * A novel study that demonstrates how HIV-1 can be inhibited by cervical mucus.

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