Immunological correlates of protection from HIV infection and disease

Abstract

The recent meeting on "Immune Correlates of Protection from HIV Infection and Disease" examined new data from a variety of preclinical and clinical settings. These new insights may facilitate vaccine design and clinical evaluation.

Immune-response profiles induced by human immunodeficiency virus type 1 vaccine DNA, protein or mixed-modality immunization: increased protection from pathogenic simian–human immunodeficiency virus viraemia with protein/DNA combination

“…However, development of a broadly effective HIV-1 vaccine has proven to be a daunting task, due to variability of the virus and the complex mechanism of envelopemediated viral entry, with minimal exposure of broadly sensitive neutralization epitopes and its interference with adaptive immune responses (Desrosiers, 2004;Heeney, 2004; Letvin et al, 2002;. However, despite these obstacles, examples from long-term nonprogressor human cohorts and proof-of-principle studies in non-human primates have revealed that control of virus load and protection from disease can be achieved in different settings (Heeney & Plotkin, 2006;Jin et al, 1999;Mascola et al, 2000;Montefiori et al, 1996;Schmitz et al, 1999). Several lines of evidence suggest that, similar to protection against retroviral infection in mice, an efficacious prophylactic HIV-1 vaccine may need to elicit both humoral and cell-mediated immune (CMI) responses (Desrosiers, 2004;Heeney, 2006;Mascola et al, 2005;Messer et al, 2004).…”

Differential CD4+versus CD8+T-Cell Responses Elicited by Different Poxvirus-Based Human Immunodeficiency Virus Type 1 Vaccine Candidates Provide Comparable Efficacies in Primates

“…Despite more than two decades of research since the discovery of HIV as the etiologic agent of AIDS, the development of an effective HIV type 1 (HIV-1) vaccine remains an unfulfilled priority. While it is generally accepted that ultimately a prophylactic HIV-1 vaccine should induce both humoral and cellmediated immune responses to a number of different HIV antigens (40,63), envelope-based immunogens capable of inducing broadly neutralizing responses currently are not available (13,79,98). Recent approaches have focused on vaccines capable of inducing potent CD8 ϩ T-cell responses to control the virus load, to reduce transmission, and to slow disease development (26,53).…”

Mapping and characterization of visna/maedi virus cytotoxic T-lymphocyte epitopes

“…A popular prime-boost regimen is that of DNA priming followed by recombinant poxvirus or adenovirus boosting (Amara et al, 2002;McDermott et al, 2005;Wang et al, 2005). Such prime-boost regimens are able to raise cellular immunity, and this has produced encouraging results with the longsought malaria vaccine (Gilbert et al, 2006;McConkey et al, 2003) and in models of HIV infection (Heeney & Plotkin, 2006). The levels of specific CTL activity in immunized sheep may be improved further if optimal immunization dose, adjuvant, route and interval are investigated (Babiuk et al, 2003;Chaplin et al, 1999;De Rose et al, 2002;Gurunathan et al, 2000;Scheerlinck et al, 2004;Watkins et al, 2005).…”

“…It is in the late stages of VISNA disease that increased virus load and antigen are seen (Brodie et al, 1992;McNeilly et al, 2007;Narayan & Clements, 1989). With immunodeficiency viruses, control of virus load has been linked to the quality and strength of the antiviral CTL response (Heeney & Plotkin, 2006).…”

“…In lentiviral infections, control of replication of HIV and SIV has been linked strongly to robust specific CD8 + CTL although CD4 + T-lymphocyte responses and antibodies are also important (Benito et al, 2004;Heeney & Plotkin, 2006;Maecker & Maino, 2003;McMichael & Rowland-Jones, 2001); protection in an FIV vaccination model has been linked to T-lymphocyte responses (Flynn et al, 1996;Hosie et al, 1998;Pu et al, 1997); and CTL are also associated with control of virus replication in horses infected with EIAV . It would therefore be reasonable to assume that protective mechanisms in VISNA will involve CTL.…”