Penny Moore Presentation - AVAC · !An$bodies,!Vaccines!and!Passive! Immunizaon! Prof Penny Moore...
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Transcript of Penny Moore Presentation - AVAC · !An$bodies,!Vaccines!and!Passive! Immunizaon! Prof Penny Moore...
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
Age Group (Years)
HIV Prevalence (N=1029)
≤16 8.4 17-18 18.6 19-20 25.4 21-22 32.8 23-24 44.8
HIV prevalence in young pregnant women
in rural Vulindlela, South Africa (2009-2012)
HIV continues to spread at high rates
in some areas!
Slide provided by Slim and Quarraisha Abdool Karim, CAPRISA
Why do we need a vaccine In sub-‐Saharan Africa, of 11 million people eligible for an@retroviral therapy, 6.2 million are receiving drugs
Vaccines are very safe, do not rely on adherence or behavior modifica@on and generally provide life-‐long protec@on
Vaccines work really well!
Vaccines are among the most successful medical
interven@ons (eradicated or controlled
smallpox, polio, measles…)
Before vaccines
ALer vaccines
HIV Vaccine Efficacy Trials To Date
No
NOTE: Phambili (HVTN 503) began to explore a regime similar to STEP in South Africa (not included).
HVTN 097 (and HVTN100) ALVAC/AIDSVAX B/E in South Africa
Phase Ib safety trial in 100 volunteers
Protocol Team Glenda Gray Surita Roux
Nicole Grunenberg Edith Swan Ying Huang Ryan Jensen NIAID/DAIDS
Patricia D’Souza Phil Renzullo Mike Pensiero
USMHRP Jerome Kim
Nelson Michael Robb O’Connel
HVTN Leadership Larry Corey
Julie McElrath Peter Gilbert Glenda Gray Sco] Hammer
Susan Buchbinder Jim Kublin SAAVI
Michelle Mulder Sanofi
Carlos DiazGranados Sanjay Phogat
GSID Carter Lee
Faruk Sinangil
Laboratory Leadership Julie McElrath
Georgia Tomaras Erica Andersen-‐Nissen
David Montefiori Lynn Morris John Hural SCHARP
Ying Huang Niya Gu
Bri]any Sanchez Peter Gilbert
In the absence of a (good) vaccine…. what can we learn from people infected with HIV, to help us make a vaccine?
All infected people make neutralizing an$bodies, but not all an$bodies are created equal….
Useful for vaccines?
Strain-‐specific an$bodies Broadly Neutralizing an$bodies
Rare infected people make good an$bodies Strain-‐specific an$bodies Broadly Neutralizing an$bodies
Gray et al, 2011
V2/glycan >12 mAbs
V3/glycan >25 mAbs
MPER >5 mAbs
Modified from Burton et al., Science 2012
Targets of broad neutralizing an$bodies
CD4bs
>25 mAbs
Fishing for broad neutralizing an$bodies
Look backwards to the unmutated common ancestor
Isola@on of broad monoclonal an@bodies
Some an$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?