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
HIV continues to HIV prevalence in young pregnant women spread at high rates in rural Vulindlela, in some areas! South Africa (2009-2012)
Age Group HIV Prevalence (Years) (N=1029) ≤16 8.4 17-18 18.6 19-20 25.4 21-22 32.8 23-24 44.8
Slide provided by Slim and Quarraisha Abdool Karim, CAPRISA What are the prospects for an HIV vaccine? 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 Before A er vaccines vaccines Vaccines work really well!
Vaccines are among the most successful medical interven ons (eradicated or controlled smallpox, polio, measles…) HIV Vaccine Efficacy Trials To Date
No
NOTE: Phambili (HVTN 503) began to explore a regime similar to STEP in South Africa (not included). The Thai trial (RV144)
31% protec on from infec on through an bodies HVTN 097 (and HVTN100) ALVAC/AIDSVAX B/E in South Africa Phase Ib safety trial in 100 volunteers
Protocol Team HVTN Leadership Laboratory Leadership Glenda Gray Larry Corey Julie McElrath Surita Roux Julie McElrath Georgia Tomaras Nicole Grunenberg Peter Gilbert Erica Andersen-Nissen Edith Swan Glenda Gray David Montefiori Ying Huang Sco Hammer Lynn Morris Ryan Jensen Susan Buchbinder John Hural NIAID/DAIDS Jim Kublin SCHARP Patricia D’Souza SAAVI Ying Huang Phil Renzullo Michelle Mulder Niya Gu Mike Pensiero Sanofi Bri any Sanchez USMHRP Carlos DiazGranados Peter Gilbert Jerome Kim Sanjay Phogat Nelson Michael GSID Robb O’Connel Carter Lee Faruk Sinangil
Reason for Op mism!
Vaccina on can alter risk of acquiring HIV infec on
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….
Strain-specific an bodies Broadly Neutralizing an bodies
Useful for vaccines? 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?
Targets of broad neutralizing an bodies
V2/glycan >12 mAbs
V3/glycan >25 mAbs
CD4bs >25 mAbs MPER >5 mAbs
Modified from Burton et al., Science 2012 What do broadly neutralizing an bodies look like? Fishing for broad neutralizing an bodies Fishing for broad neutralizing an bodies Isola on of broad monoclonal an bodies
Look backwards to the unmutated common ancestor 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! Most broad an bodies are “freaks of nature”
Long CDRH3s
Ancestor an body (how it was born) Highly mutated away from their ancestor Which pathway is easier for HIV vaccine design?
highly mutated Long CDRH3s away from their ancestor
§ Requires a B cell with long § No requirement for long arms arms - these B cells are very rare
§ Once stimulated, these can § May need high levels of develop within months, not mutation that takes years – years hard to achieve through vaccination Ac ve versus Passive/Vector-based Immunoprophylaxis (VIP)
Vaccina on Passive “vaccina on” VIP
S mula ng Produc on of an an body an bodies by response Infusion vector with protec ve an bodie s
Highly potent an bodies are being tested as “drugs” to prevent HIV Synagis, an an body used in the clinic
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.
Tes ng passive immuniza on: Does it prevent HIV infec on?
Basic research Preclinical testing Clinical trials
Laboratory Animal studies Human research Discovery Proof-of-concept Safety Efficacy
1- 2 years 1- 2 years 3-5 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?