Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys
Top Cited Papers
Open Access
- 4 January 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 482 (7383), 89-93
- https://doi.org/10.1038/nature10766
Abstract
Protective efficacy of novel vaccine candidates in rhesus monkeys opens new paths for the development of an HIV-1 vaccine. Despite the recent demonstration of partial HIV-1 vaccine efficacy in humans, the immune responses required to protect against acquisition of infection remain unclear. Here, Barouch et al. demonstrate vaccine protection against acquisition of a stringent strain of simian immunodeficiency virus (SIV) in rhesus monkeys. Two candidate vaccines expressing the Gag, Pol and Env viral antigens were tested. They observe a delay in acquisition of SIV in vaccinated monkeys following repeated challenges with SIVMAC251. Protection against acquisition is correlated with Env-specific antibody responses, which the authors postulate may be critical for delaying infection, although whether the antibodies are surrogates for protection or causal correlates is not yet clear. Preclinical studies of human immunodeficiency virus type 1 (HIV-1) vaccine candidates have typically shown post-infection virological control, but protection against acquisition of infection has previously only been reported against neutralization-sensitive virus challenges1,2,3. Here we demonstrate vaccine protection against acquisition of fully heterologous, neutralization-resistant simian immunodeficiency virus (SIV) challenges in rhesus monkeys. Adenovirus/poxvirus and adenovirus/adenovirus-vector-based vaccines expressing SIVSME543 Gag, Pol and Env antigens resulted in an 80% or greater reduction in the per-exposure probability of infection4,5 against repetitive, intrarectal SIVMAC251 challenges in rhesus monkeys. Protection against acquisition of infection showed distinct immunological correlates compared with post-infection virological control and required the inclusion of Env in the vaccine regimen. These data demonstrate the proof-of-concept that optimized HIV-1 vaccine candidates can block acquisition of stringent, heterologous, neutralization-resistant virus challenges in rhesus monkeys.This publication has 29 references indexed in Scilit:
- An HIV-1 gp120 Envelope Human Monoclonal Antibody That Recognizes a C1 Conformational Epitope Mediates Potent Antibody-Dependent Cellular Cytotoxicity (ADCC) Activity and Defines a Common ADCC Epitope in Human HIV-1 SerumJournal of Virology, 2011
- Mamu-B*08-Positive Macaques Control Simian Immunodeficiency Virus ReplicationJournal of Virology, 2007
- Comparative Seroprevalence and Immunogenicity of Six Rare Serotype Recombinant Adenovirus Vaccine Vectors from Subgroups B and DJournal of Virology, 2007
- Vaccine-Induced Cellular Immune Responses Reduce Plasma Viral Concentrations after Repeated Low-Dose Challenge with Pathogenic Simian Immunodeficiency Virus SIVmac239Journal of Virology, 2006
- The High-Frequency Major Histocompatibility Complex Class I Allele Mamu-B
*
17 Is Associated with Control of Simian Immunodeficiency Virus SIVmac239 ReplicationJournal of Virology, 2006
- Replication-Deficient Human Adenovirus Type 35 Vectors for Gene Transfer and Vaccination: Efficient Human Cell Infection and Bypass of Preexisting Adenovirus ImmunityJournal of Virology, 2003
- Expression of the Major Histocompatibility Complex Class I Molecule Mamu-A*01 Is Associated with Control of Simian Immunodeficiency Virus SIVmac239 ReplicationJournal of Virology, 2003
- Development and Homeostasis of T Cell Memory in Rhesus MacaqueThe Journal of Immunology, 2002
- Antibody from Patients with Acute Human Immunodeficiency Virus (HIV) Infection Inhibits Primary Strains of HIV Type 1 in the Presence of Natural-Killer Effector CellsJournal of Virology, 2001
- Comparative Efficacy of Recombinant Modified Vaccinia Virus Ankara Expressing Simian Immunodeficiency Virus (SIV) Gag-Pol and/or Env in Macaques Challenged with Pathogenic SIVJournal of Virology, 2000