Passive Antibody Protection In The Setting Of Active Cel

Mascola, John R.

Abstract

Current HIV vaccine candidates elicit reasonably potent cellular immune responses, but only low levels of neutralizing antibodies. Such CTL based vaccines (e.g., those based on DNA immunization) do not prevent infection, but can have a beneficial effect on disease course. In contrast, passively infused antibodies can provide complete protection, but must be administered in doses that result in serum antibody levels much higher than can be generated by current immunization strategies. In order to assess if CTL could combine with antibody to produce sterile immunity, we studied the effect of a suboptimal dose of neutralizing antibodies in animals with active immunity induced by IL2 adjuvanted DNA immunization. Using a SHIV-challenge model, this study has shown that passively infused antibody can protect against an intravenous challenge.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Intramural Research (Z01)
• Project #: 1Z01AI005009-01
• Application #: 6684226
• Study Section: (BSL)
• Support Year: 1
• Fiscal Year: 2002

Institution

• Name: Niaid Extramural Activities
• Country: United States

Publications

Keele, Brandon F; Li, Hui; Learn, Gerald H et al. (2009) Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1. J Exp Med 206:1117-34

Whitney, James B; Luedemann, Corinne; Hraber, Peter et al. (2009) T-cell vaccination reduces simian immunodeficiency virus levels in semen. J Virol 83:10840-3

Letvin, Norman L; Rao, Srini S; Dang, Vi et al. (2007) No evidence for consistent virus-specific immunity in simian immunodeficiency virus-exposed, uninfected rhesus monkeys. J Virol 81:12368-74

Letvin, Norman L; Mascola, John R; Sun, Yue et al. (2006) Preserved CD4+ central memory T cells and survival in vaccinated SIV-challenged monkeys. Science 312:1530-3

Sun, Yue; Schmitz, Jorn E; Buzby, Adam P et al. (2006) Virus-specific cellular immune correlates of survival in vaccinated monkeys after simian immunodeficiency virus challenge. J Virol 80:10950-6

Acierno, Paula M; Schmitz, Jorn E; Gorgone, Darci A et al. (2006) Preservation of functional virus-specific memory CD8+ T lymphocytes in vaccinated, simian human immunodeficiency virus-infected rhesus monkeys. J Immunol 176:5338-45

Seaman, Michael S; Santra, Sampa; Newberg, Michael H et al. (2005) Vaccine-elicited memory cytotoxic T lymphocytes contribute to Mamu-A*01-associated control of simian/human immunodeficiency virus 89.6P replication in rhesus monkeys. J Virol 79:4580-8

Mascola, John R; Sambor, Anna; Beaudry, Kristin et al. (2005) Neutralizing antibodies elicited by immunization of monkeys with DNA plasmids and recombinant adenoviral vectors expressing human immunodeficiency virus type 1 proteins. J Virol 79:771-9

Sun, Yue; Schmitz, Jorn E; Acierno, Paula M et al. (2005) Dysfunction of simian immunodeficiency virus/simian human immunodeficiency virus-induced IL-2 expression by central memory CD4+ T lymphocytes. J Immunol 174:4753-60

Zhang, Lei; Ribeiro, Ruy M; Mascola, John R et al. (2004) Effects of antibody on viral kinetics in simian/human immunodeficiency virus infection: implications for vaccination. J Virol 78:5520-2