Editors' ChoiceHIV

All systems go for HIV vaccine development

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Science Translational Medicine  25 Nov 2015:
Vol. 7, Issue 315, pp. 315ec203
DOI: 10.1126/scitranslmed.aad5913

An effective HIV vaccine would protect against what remains a life-long infection for millions of men, women, and children. Unfortunately, no roadmap exists for HIV vaccine development; what a successful immune response would look like remains unclear. Vaccines can elicit diverse antibody responses, recognizing different parts of HIV-encoded proteins, and much of vaccine development has focused on selecting the right target protein. However, the diversity of possible antibodies does not end there. Even antibodies that recognize the same protein can direct different “effector” functions—antibodies can interface with various cells in the human immune system and instruct distinct responses. Chung and colleagues have begun to categorize this antibody diversity and define immune “fingerprints” associated with HIV vaccines used in clinical trials.

The researchers set out to look for antibody correlates of vaccine-induced protection against HIV infection. They developed a quantitative approach termed “systems serology.” Antibodies were purified from each subjects’ blood and subjected to a battery of biophysical and functional tests—the scores received on each test collectively defined the subject’s vaccine response fingerprint. Antibodies from 120 subjects from four different vaccine trials were assayed for six effector functions and 58 distinct biophysical measurements. From this large dataset, patterns began to emerge. Antibody fingerprints tended to be more similar in subjects who had received related vaccines. The fingerprints also offer glimpses of connections between physical antibody diversity and associated functional diversity, including antibody features in one trial (RV144) where mild protection against HIV was observed. The serological fingerprints begin to deepen our understanding of the antibody features that separate “high risk” subjects that were vaccinated in RV144 but still acquired HIV, from the “low risk” vaccinees who had some protection from HIV.

This study develops a quantitative—and relatively unbiased—approach to examine antibody responses to vaccination. As more extensive data defines signatures for larger cohorts and for more candidate vaccines, systems serology could more precisely pinpoint the features of humoral immune responses associated with protection against HIV infection. These correlates of viral protection will need to be functionally validated in experimental systems. Looking forward, systems-scale interrogation could help to define distinct immune fingerprints that protect humans against diverse pathogens.

A. W. Chung et al., Dissecting polyclonal vaccine-induced humoral immunity against HIV using systems serology. Cell 163, 988–998 (2015). [Full Text]

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