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Human influenza virus challenge identifies cellular correlates of protection for oral vaccination. Cell host & microbe McIlwain, D. R., Chen, H., Rahil, Z., Bidoki, N. H., Jiang, S., Bjornson, Z., Kolhatkar, N. S., Martinez, C. J., Gaudillière, B., Hedou, J., Mukherjee, N., Schürch, C. M., Trejo, A., Affrime, M., Bock, B., Kim, K., Liebowitz, D., Aghaeepour, N., Tucker, S. N., Nolan, G. P. 2021

Abstract

Developing new influenza vaccines with improved performance and easier administration routes hinges on defining correlates of protection. Vaccine-elicited cellular correlates of protection for influenza in humans have not yet been demonstrated. A phase-2 double-blind randomized placebo and active (inactivated influenza vaccine) controlled study provides evidence that a human-adenovirus-5-based oral influenza vaccine tablet (VXA-A1.1) can protect from H1N1 virus challenge in humans. Mass cytometry characterization of vaccine-elicited cellular immune responses identified shared and vaccine-type-specific responses across B and T cells. For VXA-A1.1, the abundance of hemagglutinin-specific plasmablasts and plasmablasts positive for integrin a4ß7, phosphorylated STAT5, or lacking expression of CD62L at day 8 were significantly correlated with protection from developing viral shedding following virus challenge at day 90 and contributed to an effective machine learning model of protection. These findings reveal the characteristics of vaccine-elicited cellular correlates of protection for an oral influenza vaccine.

View details for DOI 10.1016/j.chom.2021.10.009

View details for PubMedID 34784508