Effector cytotoxic T lymphocyte numbers induced by vaccination should exceed levels in chronic infection for protection from HIV

Recent technological advances have revolutionised our capacity to induce cytotoxic T lymphocyte (CTL) responses with a variety of vaccine formulations and delivery systems. However, the conditions required for a CTL-inducing vaccine to provide protection from infection or disease are poorly understood, and the results of challenge experiments have not been consistent. Here we use a mathematical model to examine the requirements necessary for successful vaccination against human immunodeficiency virus (HIV) through cellular immunity. We describe the interaction between cytotoxic T cells and infected lymphocytes, capturing the essence of a persistent infection of immune cells. We conclude that to protect from infection, the cellular immune response should be boosted to levels exceeding those in chronic infection. This requires either that effector CTL exceed this threshold before infection, or that a memory CTL population is established that can yield this level of effector CTL very quickly upon infection.