2023
DOI: 10.1126/sciadv.adg3469
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Single-cycle influenza virus vaccine generates lung CD8 + Trm that cross-react against viral variants and subvert virus escape mutants

Ming Z. M. Zheng,
Tiong Kit Tan,
Fernando Villalon-Letelier
et al.

Abstract: Influenza virus–specific tissue-resident memory (Trm) CD8 + T cells located along the respiratory tract provide cross-strain protection against a breadth of influenza viruses. We show that immunization with a single-cycle influenza virus vaccine candidate (S-FLU) results in the deposition of influenza virus nucleoprotein (NP)–specific CD8 + Trm along the respiratory tract that were more cross-reactive against viral variants and less likely to drive the developmen… Show more

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Cited by 7 publications
(3 citation statements)
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References 54 publications
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“…SCIV hold an advantage over conventional live-attenuated vaccines in that they infect very few cells and so are unlikely to cause pathology or mutate or reassort into virulent forms. SCIV can be safely administered by aerosol to immunise the lung, which is associated with local immunity through tissue-resident T-cells (57) and mucosal IgA (8).…”
Section: Introductionmentioning
confidence: 99%
See 1 more Smart Citation
“…SCIV hold an advantage over conventional live-attenuated vaccines in that they infect very few cells and so are unlikely to cause pathology or mutate or reassort into virulent forms. SCIV can be safely administered by aerosol to immunise the lung, which is associated with local immunity through tissue-resident T-cells (57) and mucosal IgA (8).…”
Section: Introductionmentioning
confidence: 99%
“…Heterologous protection is induced in the absence of a neutralising antibody response to hemagglutinin at the low doses administered to the lung. Protection is associated with strong T-cell responses, including CD8+ T-cell responses in the lung (7), and a strain-specific antibody response to neuraminidase which reduces challenge virus titres in the respiratory tract in mice (13,15) and ferrets (4,18) and may (19) or may not (18) reduce challenge virus titres in pigs. No sterile immunity is evoked in any model species following administration of S-FLU to the lung.…”
Section: Introductionmentioning
confidence: 99%
“…Among the memory T cells, tissue resident memory T cells (TRM) are gaining traction as a 'ready to deploy' memory wing that is formed at the site of infection and hence acts as a barricade before the pathogens reach the circulation or lymphoid organs for the effector memory or central memory T cells to act 5 . Indeed, during IAV infection, both CD4 TRM and CD8 TRM in the lungs protect against heterologous viruses 6,7 . Compared to CD8 TRM, CD4 TRM are still understudied, despite their multifunctionality.…”
Section: Introductionmentioning
confidence: 99%