Viral vector vaccines

Abstract

Over the past two years, the SARS-CoV-2 pandemic has highlighted the impact that emerging pathogens can have on global health. The development of new and effective vaccine technologies is vital in the fight against such threats. Viral vectors are a relatively new vaccine platform that relies on recombinant viruses to deliver selected immunogens into the host. In response to the SARS-CoV-2 pandemic, the development and subsequent rollout of adenoviral vector vaccines has shown the utility, impact, scalability and efficacy of this platform. Shown to elicit strong cellular and humoral immune responses in diverse populations, these vaccine vectors will be an important approach against infectious diseases in the future.

Figure 1

Timeline showing licensing of viral vector vaccines approved for use in humans. Before 2020, only five viral vectors were licensed for use in humans, and only one by the World Health Organisation. Since 2020, five further viral vector vaccines (all containing adenoviral vector vaccines) have been licensed for human use, including three which have been licensed by the WHO.

Figure 2

Induction of innate and adaptive immune responses by adenoviral vector vaccines. Adenoviral binding occurs via the fibre protein of the Ad capsid to infection receptors, such as the coxsackievirus–adenovirus receptor (CAR) and CD46, activating entry to the cell. Secondary attachment is mediated by RGD loops on the penton protein of the Ad capsid to integrins. These binding processes themselves can trigger innate immunity, but it is the pathogen-associated molecular patterns of adenoviruses, which are recognised by cell pattern-recognition receptors (PRRs), for example, toll-like receptors (TLRs). Ad vectors are recognised by TLR2 and TLR4, which are surface receptors, and TLR9, an endosomally located receptor that senses the Ad vector genome in endosomes , . The binding of lactoferrin, a host defence peptide, to Ad vectors, appears to activate an innate immune response via TLR4-mediated internalisation . Intracellular adaptor proteins, such as MyD88, are vital for TLR signal transduction and induction of antigen-specific T-cell responses via activation of NF-κB transcription factors following Ad vector vaccine . Further, PRRs such as the cytosol DNA sensor cGAS and the receptor RIG-I area are also important for inducing innate immune signals following Ad vector vaccination .

Figure 3

Adaptive immune response to adenoviral vector vaccines. Cross-presentation of antigen occurs in antigen-presenting cells, for example, dendritic cells following phagocytososis of infected cells. Antigen is presented via MHC molecules to T cells, stimulating proliferation and differentiation of CD4+ and CD8 + T cells. B cells are activated to antigen-specific memory B cells and plasma B cells via T-dependent and T-independent mechanisms. Binding of native antigen to the B-cell receptor (BCR) delivers biochemical signals that initiate B-cell activation independent of T cells. T-cell-dependent activation occurs when the BCR internalises the antigen that is endocytosed and processed into peptides presented by class-II MHC molecules. T-helper cells recognise these and stimulate B-cell activation.