Showing papers on "SAIDS Vaccines published in 2011"

Human immunodeficiency virus-1 vaccine design: where do we go now?

Abstract: Numerous human immunodeficiency virus (HIV)-1 vaccines have been developed over the last three decades, but to date an effective HIV-1 vaccine that can be used for prophylactic or therapeutic purposes in humans has not been identified. The failures and limited successes of HIV-1 vaccines have highlighted the gaps in our knowledge with regard to fundamental immunity against HIV-1 and have provided insights for vaccine strategies that may be implemented for designing more effective HIV-1 vaccines in the future. Recent studies have shown that robust mucosal immunity, high avidity and polyfunctional T cells, and broadly neutralizing antibodies are important factors governing the induction of protective immunity against HIV-1. Furthermore, optimization of vaccine delivery methods for DNA or live viral vector-based vaccines, elucidating the immune responses of individuals who remain resistant to HIV-1 infections and also understanding the core immune responses mediating protection against simian immunodeficiency viruses (SIV) and HIV-1 in animal models following vaccination, are key aspects to be regarded for designing more effective HIV-1 vaccines in the future.

Simian Immunodeficiency Virus SIVmac239Δnef Vaccination Elicits Different Tat28-35SL8-Specific CD8+ T-Cell Clonotypes Compared to a DNA Prime/Adenovirus Type 5 Boost Regimen in Rhesus Macaques

Abstract: Different human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) vaccine vectors expressing the same viral antigens can elicit disparate T-cell responses. Within this spectrum, replicating variable vaccines, like SIVmac239Δnef, appear to generate particularly efficacious CD8+ T-cell responses. Here, we sequenced T-cell receptor β-chain (TRB) gene rearrangements from immunodominant Mamu-A*01-restricted Tat28-35SL8-specific CD8+ T-cell populations together with the corresponding viral epitope in four rhesus macaques during acute SIVmac239Δnef infection. Ultradeep pyrosequencing showed that viral variants arose with identical kinetics in SIVmac239Δnef and pathogenic SIVmac239 infection. Furthermore, distinct Tat28-35SL8-specific T-cell receptor (TCR) repertoires were elicited by SIVmac239Δnef compared to those observed following a DNA/Ad5 prime-boost regimen, likely reflecting differences in antigen sequence stability.

Vaccinology: Persistence pays off.

Abstract: Developing AIDS vaccines has been a frustrating business. A vaccine that triggers immune responses that effectively control early infection by the simian counterpart of HIV in macaques seems promising. See Letter p.523 Following some high-profile clinical trial failures in recent years, the emphasis in HIV/AIDS vaccine research has shifted away from T-cell-based vaccines that control viral replication towards vaccines that block acquisition of infection. Hansen et al. take a novel route to T-cell-based immunity, using cytomegalovirus (CMV) vectors. They find that vaccination with a rhesus-CMV-based vaccine against simian immunodeficiency virus (SIV) provides long-term protection from SIV challenge in rhesus macaques. Protection seems to be mediated by tissue-resident T-effector memory responses, suggesting that persistent vectors such as CMV may be effective in HIV/AIDS vaccines.