Fighting Fire with Fire: Immunogenicity of Viral Vectored Vaccines against COVID-19

Abstract

The persistent expansion of the coronavirus disease 2019 (COVID-19) global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires the rapid development of safe and effective countermeasures to reduce transmission, morbidity, and mortality. Several highly efficacious vaccines are actively being deployed around the globe to expedite mass vaccination and control of COVID-19. Notably, viral vectored vaccines (VVVs) are among the first to be approved for global distribution and use. In this review, we examine the humoral, cellular, and innate immune responses elicited by viral vectors, and the immune correlates of protection against COVID-19 in preclinical and clinical studies. We also discuss the durability and breadth of immune response induced by VVVs and boosters. Finally, we present challenges associated with VVVs and offer solutions for overcoming certain limitations of current vaccine regimens. Collectively, this review provides the rationale for expanding the portfolio of VVVs against SARS-CoV-2.

Keywords: COVID-19; SARS-CoV-2; T cells; antibody; viral vectored vaccine.

Figure 1

Viral vectored vaccines (VVVs) elicit innate and adaptive immune responses. Dendritic cells (DCs), macrophages, and plasmacytoid dendritic cells (pDCs) are sentinel cells that reside in tissues. Following intramuscular administration, viral particles transduce muscle cells and sentinel cells, leading to high levels of protein production (i.e., spike protein of SARS-CoV-2). DCs are present in various tissues and can capture, phagocytose, and digest antigen. As DCs upregulate pro-inflammatory cytokines, costimulatory molecules, chemokine receptors, and antigen presentation, they can traffic to the draining lymph node and prime naïve T cells by presenting them with specific antigen and costimulatory ligand. The activated T cells can proliferate and differentiate into effector or memory cells. A CD4+ T cell could differentiate into a helper T cell, such as a Th1 cell, but could also differentiate into a T follicular helper cell that assists B cells to produce antigen-specific antibodies. A CD8+ T cell could differentiate into a cytotoxic T cell that eradicates virally infected cells. While some memory T cells will persist, most effector T cells die over time. Abbreviations: GOI: gene of interest; DC: dendritic cell; pDC: plasmacytoid dendritic cell; Mφ: macrophage; Ag: antigen.