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Abstract
Intravascular delivery of broadly neutralizing antibodies (bnAbs) has shown promise for prevention and treatment of HIV infection. However, multiple IV administrations in geographic locations with poor accessibility to medical care have practical limitations. We have assessed the efficacy of plant-derived PGT121 delivered subcutaneously (SC) against pre-and post-intravaginal challenge using a rigorous SHIV-SF162P3 macaque protection model. SC administered PGT121 exhibited a longer serum half-life than IV administration and was more consistent than intramuscular delivery. A dose of 3.5mg/kg PGT121 prevented infection at a minimum ID50 neutralization titer of 1:295 while 5mg/kg protected five of six macaques when delivered immediately post-challenge. These results suggest the utility of plant-derived bnAbs delivered SC for HIV prevention.
Highlights
Passive administration of the potent HIV bnAb PGT121 when delivered to macaques intravenously (IV) has been shown to be efficacious in preventing SHIV infection or reducing viral load (VL) [1,2]
In order to establish the time of peak PGT121 levels (Tmax) following parenteral administration and the time of challenge to assess optimal protection, preliminary studies were performed in which two African Green monkeys each received 5mg/kg of PGT121 by either SC or IM delivery and the pharmacokinetics monitored from 4 hr to 14 days
In terms of pharmacokinetic parameters following different routes of delivery shown in Fig 1, the very high potency of recent HIV bnAbs means that their Cmax values, highest after IV infusion, are less critical than their half-life values and that the larger MRT and T1/2 after parenteral injections, administered as a single injection or as small repeated injections, may afford a more practical delivery system than IV delivery, especially if bnAbs can be self-administered
Summary
Passive administration of the potent HIV bnAb PGT121 when delivered to macaques intravenously (IV) has been shown to be efficacious in preventing SHIV infection or reducing viral load (VL) [1,2]. For the prevention of mother-to-child transmission (MTCT) in resource poor countries, IV injections are not practical and alternate routes of delivery should be considered for optimal benefit and protection. In this context, virtually all human vaccines currently on the market are administered via subcutaneous (SC) or intramuscular (IM) routes with SC delivery being most commonly used when.
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