An$bodies, Vaccines and Passive Immuniza$on Prof Penny Moore National Institute for Communicable Diseases, a division of the National Health Laboratory Service of South Africa, and the University of the Witwatersrand, Johannesburg, South Africa AVAC, 2015
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An$bodies, Vaccines and Passive
Immuniza$on
Prof Penny Moore National Institute for Communicable Diseases, a division of the National Health Laboratory Service of South Africa, and the University of the Witwatersrand, Johannesburg, South Africa
Rare infected people make good an$bodies Strain-‐specific an$bodies Broadly Neutralizing an$bodies
Gray et al, 2011
Where do these an$bodies bind – can we iden$fy viral vulnerabili$es?
V2/glycan >12 mAbs
V3/glycan >25 mAbs
MPER >5 mAbs
Modified from Burton et al., Science 2012
Targets of broad neutralizing an$bodies
CD4bs
>25 mAbs
What do broadly neutralizing an$bodies look like?
Fishing for broad neutralizing an$bodies
Fishing for broad neutralizing an$bodies
Look backwards to the unmutated common ancestor
Isola@on of broad monoclonal an@bodies
Fishing for broad neutralizing an$bodies
Some an$bodies are INCREDIBLY broad!
§ We can use these antibodies to understand how they develop and try yo mimic this in vaccines
§ But also more directly in passive immunization studies!
Long CDRH3s
Highly mutated away from their ancestor
Most broad an$bodies are “freaks of nature”
Ancestor an@body (how it was born)
Long CDRH3s highly mutated away from their
ancestor
Which pathway is easier for HIV vaccine design?
§ Requires a B cell with long arms - these B cells are very rare
§ Once stimulated, these can develop within months, not years
§ No requirement for long arms
§ May need high levels of mutation that takes years – hard to achieve through vaccination
Ac$ve versus Passive/Vector-‐based Immunoprophylaxis (VIP)
Vaccina@on
S@mula@ng an an@body response
Passive “vaccina@on”
Infusion with protec@ve an@bodies
Produc@on of an@bodies by vector
VIP
Highly potent an$bodies are being tested as “drugs” to
prevent HIV
Synagis is used to prevent a serious lung disease caused by respiratory syncy@al virus (RSV) . It is used in infants at high-‐risk because of prematurity or congenital heart disease. An@body is dosed once a month for the dura@on of the RSV season.
Synagis, an an$body used in the clinic
Basic research
Preclinical testing
Clinical trials
Discovery Human research Animal studies Laboratory
Proof-of-concept
1-‐ 2 years 3-‐5 years
Tes$ng passive immuniza$on: Does it prevent HIV infec$on?
Safety Efficacy
1-‐ 2 years
Conclusions • Prospects for a vaccine are be]er than ever, but this will s@ll take @me
• Passive immuniza@on trials in humans will likely provide another HIV preven@on tool and may also be useful for trea@ng people already infected.
• Passive immuniza@on will also provide us with informa@on we need to drive vaccine design such as which an@body, how much, where?