486. A/California/07/2009-pdm-like (H1N1) Influenza Virus Controlled Human Infection Model (CHIM) Activates Various Immune Cells Despite Induction of Mild Symptomatology


 
 
 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.
 
 
 
 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.
 
 
 
 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.
 
 
 
 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.
 
 
 
 Catherine J. Luke, Ph.D., GSK: Spouse is an employee of GSK Justin Ortiz, MD, Moderna: Advisor/Consultant|Pfizer: Advisor/Consultant.
