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It’s amazing how far we have come in the potential of neutralizing monoclonal antibodies against HIV. John Mascola from the Vaccine Research Centre gave a great plenary on “Harnessing antibodies for HIV prevention and treatment.”
Antibodies have been used in infectious diseases for passive immunization eg RSV, zoster, hepatitis B.
Many potent broadly neutralizing antibodies have been discovered in HIV since 2009, which can bind to various sites on HIV gp41 and block viral entry into cells. These newly discovered antibodies are 500x more potent than previously and more are being found.
Studies in monkeys have demonstrated that passive immunization with these newer antibodies such as VRC01 can prevent SHIV infection.
There are early phase studies in humans. The treatment appears safe and well tolerated. Protective levels of antibodies remain in circulation for 2 months – this period can be extended by creating mutations in the Fc region that increase the antibody affinity.
Can antibodies protect against infection in humans? How much is required (as more potent antibodies are discovered, they will require lower doses and last longer, thus reducing cost. Lower dosage also means they can be administered subcutaneously rather than IV). There also needs a greater understanding of how and where exactly these antibodies work in the body.
A large scale HIV prevention study is planned using broadly neutralizing antibodies to provide antibody mediated protection in 2400 MSM in North and South America and 15000 women in Africa. The goal – safe effective administration sc every 4/12 for PrEP.
There needs to be protection against wide variety of HIV strains – combining antibodies acting at different sites will achieve this.
Other potential roles for these neutralizing antibodies include preventing mother to child transmission intrapartum and with breast feeding – animal models show this is viable.
Neutralizing antibodies may also have a role in treating HIV infection – either alone, or complementary to ART. They may be able to reduce viraemia in primary infection, or in those with chronic infection, to treat HIV, and to assist in killing of infected cells by marshalling immune response.
So while there is work to do in translating this knowledge into viable HIV prevention and treatment options, there has been major progress in this area. Watch this space.