Shingai Masashi, Donau Olivia K, Plishka Ronald J, Buckler-White Alicia, Mascola John R, Nabel Gary J, Nason Martha C, Montefiori David, Moldt Brian, Poignard Pascal, Diskin Ron, Bjorkman Pamela J, Eckhaus Michael A, Klein Florian, Mouquet Hugo, Cetrulo Lorenzi Julio Cesar, Gazumyan Anna, Burton Dennis R, Nussenzweig Michel C, Martin Malcolm A, Nishimura Yoshiaki
Laboratory of Molecular Microbiology, Virology Laboratory, Vaccine Research Center, and Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Department of Surgery, Duke University Medical Center, Durham, NC 27710.
J Exp Med. 2014 Sep 22;211(10):2061-74. doi: 10.1084/jem.20132494. Epub 2014 Aug 25.
It is widely appreciated that effective human vaccines directed against viral pathogens elicit neutralizing antibodies (NAbs). The passive transfer of anti-HIV-1 NAbs conferring sterilizing immunity to macaques has been used to determine the plasma neutralization titers, which must be present at the time of exposure, to prevent acquisition of SIV/HIV chimeric virus (SHIV) infections. We administered five recently isolated potent and broadly acting anti-HIV neutralizing monoclonal antibodies (mAbs) to rhesus macaques and challenged them intrarectally 24 h later with either of two different R5-tropic SHIVs. By combining the results obtained from 60 challenged animals, we determined that the protective neutralization titer in plasma preventing virus infection in 50% of the exposed monkeys was relatively modest (∼1:100) and potentially achievable by vaccination.
人们普遍认识到，针对病毒病原体的有效人类疫苗会引发中和抗体（NAbs）。赋予猕猴绝育免疫力的抗HIV-1 NAbs的被动转移已被用于确定血浆中和滴度，该滴度必须在接触时存在，以防止获得SIV/HIV嵌合病毒（SHIV）感染。我们给恒河猴注射了五种最近分离出的强效且具有广泛作用的抗HIV中和单克隆抗体（mAbs），并在24小时后用两种不同的R5嗜性SHIV之一经直肠对它们进行攻击。通过合并从60只受攻击动物获得的结果，我们确定血浆中防止50%受暴露猴子感染病毒的保护性中和滴度相对适中（约1:100），并且有可能通过疫苗接种实现。
