Year in Review | Published:

VACCINES IN 2018

Advancing an HIV vaccine; advancing vaccinology

Of any pathogen, HIV provides perhaps the greatest challenge to successful vaccine development. Nevertheless, progress continued to be made in 2018; new vaccine concepts entered the clinic and new insights were obtained in basic research that will ultimately help to guide rational vaccine design against many ‘difficult’ pathogens.

Key advances

  • The fusion peptide of HIV Envelope (Env) has emerged as a potential vaccine target.

  • Naive B cell precursor frequencies and antigen affinities are crucial in considering the likelihood of success with a germline-targeting immunogen.

  • Off-target responses to immunogens can be reduced by glycan masking of irrelevant epitopes.

  • Neutralization, but not other immune parameters, correlates with HIV trimer vaccine-induced protection against viral challenge in a monkey model.

  • Electron microscopy is a rapid method to determine the specificities present in a polyclonal antibody response following vaccination or infection.

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References

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    Escolano, A., Dosenovic, P. & Nussenzweig, M. C. Progress toward active or passive HIV-1 vaccination. J. Exp. Med. 214, 3–16 (2017).

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    HIV Prevention Trials Network & HIV Vaccine Trials Network. AMP HIV Prevention Study. AMP Study https://ampstudy.org (2018).

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    Andrabi, R., Bhiman, J. N. & Burton, D. R. Strategies for a multi-stage neutralizing antibody-based HIV vaccine. Curr. Opin. Immunol. 53, 143–151 (2018).

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    Xu, K. et al. Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1. Nat. Med. 24, 857–867 (2018).

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    Jardine, J. G. et al. HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen. Science 351, 1458–1463 (2016).

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    Abbott, R. K. et al. Precursor frequency and affinity determine B cell competitive fitness in germinal centers, tested with germline-targeting HIV vaccine immunogens. Immunity 48, 133–146 (2018).

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    Dosenovic, P. et al. Anti-HIV-1 B cell responses are dependent on B cell precursor frequency and antigen-binding affinity. Proc. Natl Acad. Sci. USA 115, 4743–4748 (2018).

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    Duan, H. et al. Glycan masking focuses immune responses to the HIV-1 CD4-binding site and enhances elicitation of VRC01-class precursor antibodies. Immunity 49, 301–311 (2018).

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    Pauthner, M. P. et al.Vaccine-induced protection from homologous tier 2 SHIV challenge in nonhuman primates depends on serum-neutralizing antibody titers. Immunity https://doi.org/10.1016/j.immuni.2018.11.011 (2018).

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    Bianchi, M. et al. Electron-microscopy-based epitope mapping defines specificities of polyclonal antibodies elicited during HIV-1 BG505 envelope trimer immunization. Immunity 49, 288–300 (2018).

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Acknowledgements

Thanks to S. Crotty, L. Hangartner, J. Mascola and A. Ward for comments on the manuscript and to the National Institute of Allergy and Infectious Diseases (NIAID), International AIDS Vaccine Initiative (IAVI) and the Bill & Melinda Gates Foundation for financial support.

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Competing interests

The author declares no competing interests.

Correspondence to Dennis R. Burton.

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Fig. 1: A sequential HIV immunization strategy.