Emerging concepts on T follicular helper cell dynamics in HIV infection.
Pissani F, Streeck H Trends Immunol. 2014 Jun;35(6):278-86.
Inducing cross-reactive broadly neutralizing antibody (bNAb) responses to HIV through vaccination remains an insurmountable challenge. T follicular helper (TFH) cells are fundamental for the development of antigen-specific antibody responses and therefore crucial for anti-HIV vaccine design. Here, we review recent studies supporting an intricate involvement of TFH cells in HIV pathogenesis and bNAb development during HIV infection. We also examine emerging data suggesting that TFH cell responses may be traceable in peripheral blood, and discuss the implications of these findings in the context of vaccine design and future research in TFH cell immunobiology.
Harnessing CD4⁺ T cell responses in HIV vaccine development.
Streeck H, D’Souza MP, Littman DR, Crotty S. Nat Med. 2013 Feb;19(2):143-9.
CD4(+) T cells can perform a panoply of tasks to shape an effective response against a pathogen. Limited attention has been paid to the potential importance of functional CD4(+) T cell responses in the context of the development of next-generation vaccines, including HIV vaccines. Many CD4(+) T cell functions are newly appreciated and only partially understood. A workshop was held as a forum to bring together a small group of experts to exchange ideas on the role of CD4(+) T cells in developing durable functional antibody responses, via follicular helper T cells, as well as on the roles of CD4(+) T cells in other aspects of protective immunity. Here we discuss whether CD4(+) T cell responses may represent a beneficial component of an efficacious HIV vaccine.
A Blueprint for HIV Vaccine Discovery.
Burton DR, Ahmed R, Barouch DH, Butera ST, Crotty S, Godzik A, Kaufmann DE, McElrath MJ, Nussenzweig MC, Pulendran B, Scanlan CN, Schief WR, Silvestri G, Streeck H, Walker BD, Walker LM, Ward AB, Wilson IA, Wyatt R. Cell Host Microbe. 2012 Oct 18;12(4):396-407.
Despite numerous attempts over many years to develop an HIV vaccine based on classical strategies, none has convincingly succeeded to date. A number of approaches are being pursued in the field, including building upon possible efficacy indicated by the recent RV144 clinical trial, which combined two HIV vaccines. Here, we argue for an approach based, in part, on understanding the HIV envelope spike and its interaction with broadly neutralizing antibodies (bnAbs) at the molecular level and using this understanding to design immunogens as possible vaccines. BnAbs can protect against virus challenge in animal models, and many such antibodies have been isolated recently. We further propose that studies focused on how best to provide T cell help to B cells that produce bnAbs are crucial for optimal immunization strategies. The synthesis of rational immunogen design and immunization strategies, together with iterative improvements, offers great promise for advancing toward an HIV vaccine.
Cytolytic CD4(+) T cells in viral immunity.
Soghoian DZ, Streeck H. Expert Rev Vaccines. 2010 Dec;9(12):1453-63.
It is generally believed that the role of CD4(+) T cells is to coordinate the different arms of the adaptive immune system to shape an effective response against a pathogen and regulate nonessential or deleterious activities. However, a growing body of evidence suggests that effector CD4(+) T cells can directly display potent antiviral activity themselves. The presence of cytolytic CD4(+) T cells has been demonstrated in the immune response to numerous viral infections in both humans and in animal models and it is likely that they play a critical role in the control of viral replication in vivo. This article describes the current research on virus-specific cytolytic CD4(+) T cells, with a focus on HIV-1 infection and the implications that this immune response has for vaccine design.