The gift of preexisting immunity for developing an alternative vaccine strategy
Kim A. Tran, Maziar Divangahi
Kim A. Tran, Maziar Divangahi
Published December 1, 2023
Citation Information: J Clin Invest. 2023;133(23):e174952. https://doi.org/10.1172/JCI174952.
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Commentary

The gift of preexisting immunity for developing an alternative vaccine strategy

Abstract

Despite the worldwide application of vaccination and other antiviral interventions, pulmonary viral infections remain a persistent threat to human health. The 1918 influenza pandemic killed more than 40 million people in just one year, and the SARS-CoV-2 pandemic has killed more than 6.9 million people since 2019. While the current approved COVID-19 vaccines are administered parenterally and induce systemic immunity, they only prevent the progression to severe disease. Thus, other vaccine platforms are still needed for completely preventing the disease and subsequent transmission. In this issue of the JCI, Kawai et al. present an adjuvant-free subunit (RBD-HA) fusion vaccine, which produces robust IgG and IgA antibody responses against SARS-CoV-2, enriched within the nasal cavity, by using the host’s preexisting immunity to influenza infection. This preclinical study has tremendous implications for future mucosal vaccine design and provides a roadmap for generating a safer and effective intranasal vaccine against pulmonary infections.

Authors

Kim A. Tran, Maziar Divangahi

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Figure 1

RBD-HA immunizes IAV-infected mice against SARS-CoV-2.

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RBD-HA immunizes IAV-infected mice against SARS-CoV-2. Previous exposure...
Previous exposure to IAV infection results in the generation of specific antibodies to the immunodominant glycoprotein HA and activation of CD4+ memory T cells. Upon immunization with RBD-HA vaccine, circulating HA-specific IgG antibodies can cross the mucosal barrier and recognize HA antigens in the nasal cavity. Only HA-IgG–bound particles will have the capacity to cross the mucosal barrier potentially through transport via FcRn. Bound antigens will enter into the mucosa-associated tissue that is rich with immune cells (B cells, DCs, CD4+ memory T cells) for antigen presentation. The synergistic action of immune cells in the mucosal tissue will generate RBD-spike–specific IgG and IgA antibodies, which can cross into the nasal cavity and block viral entry during subsequent SARS-CoV-2 infection.