Contrasting B cell- and T cell-based protective vaccines

Abstract

A substantial research effort is devoted to the development of vaccines based on T cells. Such a vaccine would provide a means to protect against infection with HIV and stop the current pandemic. Here we investigate the possibility to develop a protective T cellbased vaccine. We do this by means of a mathematical model which describes the dynamics of a pathogen and the immune system in the early stages of infection. We compare an immune response that is near immediate-as is the case for a humoral response-with that of a response in which the effector cells have to be formed from precursor cells-as occurs in T cell responses. The latter applies to a T cell-based vaccine. A near immediate response is associated with a threshold number of effector cells above which an infection cannot take hold. For a T cell-based vaccine this threshold increases with the amount of antigen the immune system is exposed to. For small initial doses, as one would naturally expect to occur, this gives rise to impractically large thresholds. Thus, although a T cell vaccine might work against a high dose exposure, it might fail when exposed against to a low-dose exposure. This limits, we argue, the efficacy of T cell-based vaccines. r

Understanding the Failure of CD8+T-Cell Vaccination against Simian/Human Immunodeficiency Virus

“…The only way to control a rapidly replicating virus by slow CD8 ϩ T-cell immunity is to prevent the initial viral outgrowth (see Appendix) (76). In the absence of a persisting infection that is maintaining an active local effector population at the site of infection, CD8 ϩ T-cell recruitment into the local tissues is too slow to allow for swift initial control (1,21,22,45), and CD8 ϩ T cells are expected to fail on rapidly growing viruses.…”

Infection dynamics in HIV-specific CD4 T cells: Does a CD4 T cell boost benefit the host or the virus?

“…This may occur if in addition to the helper cell response, the CD8 cell response has also been boosted by vaccination. Whether CD8 cell vaccination can lead to this outcome may, however, also depend on the details of the vaccination [29]. If vaccination maintains active effector responses by providing continuous antigenic stimulation, this argument would certainly apply.…”

A clinically parameterized mathematical model of Shigella immunity to inform vaccine design

“…Mathematical models of immune responses to viruses and some bacteria are increasingly common (e.g., [ 21 – 26 ]), and a few mathematical studies have examined in-host pathogen interactions with vaccines (e.g., [ 27 , 28 ]). Our 2013 paper [ 29 ] introduced the first mathematical investigation of the immune response against Shigella ; with it, we established a foundational mathematical framework for identifying key bacterial and immune vaccine targets [ 29 ].…”