Vaccine-Induced CD8+ T Cell Responses in Children: A Review of Age-Specific Molecular Determinants Contributing to Antigen Cross-Presentation

Abstract

Infections are most common and most severe at the extremes of age, the young and the elderly. Vaccination can be a key approach to enhance immunogenicity and protection against pathogens in these vulnerable populations, who have a functionally distinct immune system compared to other age groups. More than 50% of the vaccine market is for pediatric use, yet to date vaccine development is often empiric and not tailored to molecular distinctions in innate and adaptive immune activation in early life. With modern vaccine development shifting from whole-cell based vaccines to subunit vaccines also comes the need for formulations that can elicit a CD8+ T cell response when needed, for example, by promoting antigen cross-presentation. While our group and others have identified many cellular and molecular determinants of successful activation of antigen-presenting cells, B cells and CD4+ T cells in early life, much less is known about the ontogeny of CD8+ T cell induction. In this review, we summarize the literature pertaining to the frequency and phenotype of newborn and infant CD8+ T cells, and any evidence of induction of CD8+ T cells by currently licensed pediatric vaccine formulations. In addition, we review the molecular determinants of antigen cross-presentation on MHC I and successful CD8+ T cell induction and discuss potential distinctions that can be made in children. Finally, we discuss recent advances in development of novel adjuvants and provide future directions for basic and translational research in this area.

Chimeric Fusion (F) and Attachment (G) Glycoprotein Antigen Delivery by mRNA as a Candidate Nipah Vaccine

“…The pre-F/G chimera elicited CD4 + T cell responses, CD8 + T cells and induced CD4 + Tfh cells to both F and G in a mRNA dose-dependent manner ( Figures 6A–C ). Immunization with either dose of pre-F/G mRNA resulted in significantly more CD8 + T cells than the 10 µg of the same protein ( Figure 6C ), in agreement with other reports demonstrating stronger CD8 + T cell induction via nucleic acid immunization than subunit protein ( 78 , 79 ). The increased breadth and frequency of T cell responses elicited by pre-F/G immunogens combined with neutralizing antibody response to both glycoproteins indicate an advantage of including both in the selected immunogen.…”

Photochemically-Mediated Inflammation and Cross-Presentation of Mycobacterium bovis BCG Proteins Stimulates Strong CD4 and CD8 T-Cell Responses in Mice

“…While viral or nucleic acid vaccines (76)(77)(78)(79) deliver genetic material into the host APCs, potentially resulting in endogenous transcription and subsequent translation into proteins and therefore effective presentation on MHC class I, protein vaccines or whole-cell bacterial vaccines usually do not gain cytosolic access. Adjuvants promoting CD8mediated immunity are therefore a key element for developing effective subunit TB vaccines (80,81). Many adjuvants such as aluminum salts, TLR ligands, or synthetic particles may strengthen immunogenicity, albeit cross-presentation of CD8 T-cell epitopes may still be ineffective.…”

Endothelial Dysfunction through Oxidatively Generated Epigenetic Mark in Respiratory Viral Infections

“…Newborns cannot be expected to mount a sufficiently strong secretion of IFNs to respond against RSV, while the elderly do not respond well to vaccinations in general [53]. There are vaccine candidates under development, yet it remains a major challenge to immunize certain population categories [54].…”