Abstract
Abstract Background Influenza vaccines require yearly updates due to constant antigenic drift. Improvement of current vaccines requires a deep understanding of the pathogen as well as immunity to the virus. Controlled Human Infection Models (CHIM) provide opportunities to i) test new vaccine approaches in a controlled environment and, ii) better understand host immunity. The University of Maryland School of Medicine (UMSOM) was one of four clinical sites to conduct an H1N1 influenza A virus (IAV) (A/California/07/2009-pdm-like) challenge in 2019. Methods Healthy adult volunteers were intranasally challenged with IAV (2 mL of ∼5x10e6 TCID50/mL). After challenge (Day 1), volunteers were assessed for the development of clinical symptoms, virus shedding, development of anti-influenza antibodies (reported elsewhere). Blood specimens were collected at Days -2, 4, 6, 8, 15 and 61 to assess changes in cellular immunity (flow cytometry and ELISpot). Our sub-study included subjects (n=20) from the UMSOM cohort only. Results B cell compartment, ASC (plasmablast) responses to homologous hemagglutinin (HA) and neuraminidase (NA) peaked at Day 8. Anti-HA IgG and IgA ASC responses were present in 95% and 75% participants, respectively. NA IgG and IgA ASC responses were present in 60% and 50% of participants, respectively. In the innate compartment, plasmocytoid dendritic cells (pDCs) as well as Classical (CM), intermediate (IM) and non-classical (NCM) monocytes increased in frequency at various timepoints post-challenge. Myeloid DC (mDC), pDC, CM and IM also upregulated expression of CD38 and/or HLA-DR at specific timepoints. The frequency of the CD16+CD56+ natural killer (NK) cell subset and NKT cells were also increased post-challenge. Among T cells, CD4 and CD8 T effector memory (TEM) and TEM CD45RA+ (TEMRA) were activated (CD38+ HLA-DR+) after challenge (Figure 1). CD4 T follicular helper cells (TFH)-17, TFH-1 and TFH-2 were activated (CD38+ ICOS+) at various timepoints post-challenge. Figure 1.Overview of cellular responses to Influenza CHIM. The heat maps show changes in population frequency and/or expression of activation markers in innate (DC and monocytes) and T cells after challenge (D-2 pre-challenge). Each square displays the mean (n=20) of the population/marker. The color scale indicates the degree of change. Conclusion After influenza CHIM, all cell populations assessed showed signs of activation at diverse time-points. The relationship between the presence of pre-existing protective immunity (HAI >40) and degree of immune activation is still under analysis. Disclosures Catherine J. Luke, Ph.D., GSK: Spouse is an employee of GSK Justin Ortiz, MD, Moderna: Advisor/Consultant|Pfizer: Advisor/Consultant.
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