Harnessing the Power of T Cells: The Promising Hope for a Universal Influenza Vaccine

Abstract

Next-generation vaccines that utilize T cells could potentially overcome the limitations of current influenza vaccines that rely on antibodies to provide narrow subtype-specific protection and are prone to antigenic mismatch with circulating strains. Evidence from animal models shows that T cells can provide heterosubtypic protection and are crucial for immune control of influenza virus infections. This has provided hope for the design of a universal vaccine able to prime against diverse influenza virus strains and subtypes. However, multiple hurdles exist for the realisation of a universal T cell vaccine. Overall primary concerns are: extrapolating human clinical studies, seeding durable effective T cell resident memory (Trm), population human leucocyte antigen (HLA) coverage, and the potential for T cell-mediated immune escape. Further comprehensive human clinical data is needed during natural infection to validate the protective role T cells play during infection in the absence of antibodies. Furthermore, fundamental questions still exist regarding the site, longevity and duration, quantity, and phenotype of T cells needed for optimal protection. Standardised experimental methods, and eventually simplified commercial assays, to assess peripheral influenza-specific T cell responses are needed for larger-scale clinical studies of T cells as a correlate of protection against influenza infection. The design and implementation of a T cell-inducing vaccine will require a consensus on the level of protection acceptable in the community, which may not provide sterilizing immunity but could protect the individual from severe disease, reduce the length of infection, and potentially reduce transmission in the community. Therefore, increasing the standard of care potentially offered by T cell vaccines should be considered in the context of pandemic preparedness and zoonotic infections, and in combination with improved antibody vaccine targeting methods. Current pandemic vaccine preparedness measures and ongoing clinical trials under-utilise T cell-inducing vaccines, reflecting the myriad questions that remain about how, when, where, and which T cells are needed to fight influenza virus infection. This review aims to bring together basic fundamentals of T cell biology with human clinical data, which need to be considered for the implementation of a universal vaccine against influenza that harnesses the power of T cells.

Tissue-resident CD4+T helper cells assist protective respiratory mucosal B and CD8+T cell memory responses

“…Much of attention has been given to the development of potential universal influenza vaccines recently. The common goals of various universal influenza vaccine candidates are to induce broadly neutralizing influenza Ab, strong CD8 + memory T cell responses against conserved epitopes and/or high levels of localized lung-resident mucosal immunity that can restrict viral spreading early 72, 73, 74, 75 . Due to the high mutation rates of influenza viruses, it is conceivable that the induction of “all inclusive” immune responses, i.e.…”

Quantifying memory CD8 T cell-mediated immune pressure on influenza A virus infectionin vivo

“…T cell-inducing vaccines have been proposed as a potential means to lessen the burden of influenza disease due to their ability to limit viral replication and immunopathology and the high conservation of immunodominant CD8 T cell across different influenza strains [6][7][8][9][10]. Whether these vaccines may drive the evolution of cellular immune escape influenza variants has not been investi- Why is the selective advantage conferred by escaping the NP366-374-specific memory CD8…”

“…Vaccines that induce broadly-neutralizing antibodies against the conserved regions of hemagglutinin (HA) and/or neuraminidase (NA), and vaccines that induce T cells targeting the conserved epitopes on the internal proteins (e.g., nucleoprotein [NP]), have been proposed to overcome these drawbacks [6][7][8][9][10].…”

<p>Immunoinformatics and Vaccine Development: An Overview</p>

“…T cell responses to viral pathogens differ from one patient to the other, basically because of the expression of differing HLA (MHC) alleles which determine the several viral amino acid sequence brought to the T cells to read. 136,137 It is most likely that during an infection, diverse epitopes are usually presented to the T cells to read owing to the several forms of HLA alleles and also because each human person expresses six HLA Class I and six HLA Class II alleles. 138 Now, antibody-binding sites in a given HLA (MHC) molecule are mostly prediction-servers predetermined on the basis of particular binding motifs and the anchor residues.…”