Assessing the generation of tissue resident memory T cells by vaccines

Abstract

Vaccines have been a hugely successful public health intervention, virtually eliminating many once common diseases of childhood. However, they have had less success in controlling endemic pathogens including Mycobacterium tuberculosis , herpesviruses and HIV. A focus on vaccine-mediated generation of neutralizing antibodies, which has been a successful approach for some pathogens, has been complicated by the emergence of escape variants, which has been seen for pathogens such as influenza viruses and SARS-CoV-2, as well as for HIV-1. We discuss how vaccination strategies aimed at generating a broad and robust T cell response may offer superior protection against pathogens, particularly those that have been observed to mutate rapidly. In particular, we consider here how a focus on generating resident memory T cells may be uniquely effective for providing immunity to pathogens that typically infect (or become reactivated in) the skin, respiratory mucosa or other barrier tissues.

A mass cytometry approach to track the evolution of T cell responses during infection and immunotherapy by paired T cell receptor repertoire and T cell differentiation state analysis

“…Our data also suggests that influenza vaccination improves the immune response to subsequent infection by driving a subset of Vβ8.3 + CD8 + T cells to take on a tissue resident memory-like differentiation state. Tissue resident memory cells allow for control of broad viral serotypes against several viruses ranging from influenza to SARS-COV-2 52 . The Vβ8.3 + Trm-like cells were the most expanded population during infection in mice that were previously vaccinated.…”

A randomized double-blind Phase IIb trial to evaluate the efficacy of ChAd63-KH for the treatment of post kala-azar dermal leishmaniasis

“…Pragmatically, single dose schedules have multiple benefits in a LMIC setting, including reducing logistical complexities and a reduction in cost, not least due to the savings from not requiring manufacture of two clinical grade vaccines. Similarly, intramuscular dosing is preferred in many clinical situations due to ease of administration and standardisation and tolerability but may not be the most appropriate route for eliciting skin homing CD8 + T cells 43 . Thus, we cannot rule out that an efficacy signal may have been observed using a repeat dosing schedule, by extending the period of follow up, by use of a heterologous prime-boost strategy 41 and / or by varying route of administration.…”

Functional heterogeneity of human skin‐resident memory T cells in health and disease

“…122 In later stages of epithelial injury, skin-resident γδ-T cells and BATF + CCR8 + skin T regs are thought to promote physiological wound healing by partaking in a tightly regulated response comprising pro-/anti-inflammatory signals and growth factors, 123,124 whereas increased numbers of TNFα-producing CD8 + memory T cells were found in hypertrophic (keloid) scars. 125 As first line of defense, T RM are considered important targets in vaccine design, 126 and the route of vaccine administration will be critical to promote the generation of protective CD8 + T RM in barrier tissues. In orthopoxvirus and modified vaccinia Ankara virus vaccination, administration via skin scarification resulted in superior skin T RM -mediated immunity compared with classical vaccination routes, including subcutaneous or intramuscular vaccination.…”