Baseline Levels of Influenza-Specific B Cells and T Cell Responses Modulate Human Immune Responses to Swine Variant Influenza A/H3N2 Vaccine
Lilin Lai,
Nadine Rouphael,
Yongxian Xu,
Amy C. Sherman,
Srilatha Edupuganti,
Evan J. Anderson,
Pamela Lankford-Turner,
Dongli Wang,
Wendy Keitel,
Monica M. McNeal,
Kaitlyn Cross,
Heather Hill,
Abbie R. Bellamy,
Mark J. Mulligan
Affiliations
Lilin Lai
The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 500 Irvin Court, Decatur, GA 30030, USA
Nadine Rouphael
The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 500 Irvin Court, Decatur, GA 30030, USA
Yongxian Xu
The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 500 Irvin Court, Decatur, GA 30030, USA
Amy C. Sherman
The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 500 Irvin Court, Decatur, GA 30030, USA
Srilatha Edupuganti
The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 500 Irvin Court, Decatur, GA 30030, USA
Evan J. Anderson
Emory Children Center, Departments of Pediatrics and Medicine, Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA 30322, USA
Pamela Lankford-Turner
The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 500 Irvin Court, Decatur, GA 30030, USA
Dongli Wang
The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 500 Irvin Court, Decatur, GA 30030, USA
Wendy Keitel
Departments of Molecular Virology & Microbiology and Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
Monica M. McNeal
Department of Pediatrics, University of Cincinnati College of Medicine, Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
Kaitlyn Cross
Emmes, 401 N. Washington St., Suite 700, Rockville, MD 20850, USA
Heather Hill
Emmes, 401 N. Washington St., Suite 700, Rockville, MD 20850, USA
Abbie R. Bellamy
Emmes, 401 N. Washington St., Suite 700, Rockville, MD 20850, USA
Mark J. Mulligan
New York University Langone Medical Center, Alexandria Center for Life Sciences (West Tower), 430 E 29th St, Room 304, New York, NY 10016, USA
The cellular immune responses elicited by an investigational vaccine against an emergent variant of influenza (H3N2v) are not fully understood. Twenty-five subjects, enrolled in an investigational influenza A/H3N2v vaccine study, who received two doses of vaccine 21 days apart, were included in a sub-study of cellular immune responses. H3N2v-specific plasmablasts were determined by ELISpot 8 days after each vaccine dose and H3N2v specific CD4+ T cells were quantified by intracellular cytokine and CD154 (CD40 ligand) staining before vaccination, 8 and 21 days after each vaccine dose. Results: 95% (19/20) and 96% (24/25) subjects had pre-existing H3N2v specific memory B, and T cell responses, respectively. Plasmablast responses at Day 8 after the first vaccine administration were detected against contemporary H3N2 strains and correlated with hemagglutination inhibition HAI (IgG: p = 0.018; IgA: p < 0.001) and Neut (IgG: p = 0.038; IgA: p = 0.021) titers and with memory B cell frequency at baseline (IgA: r = 0.76, p < 0.001; IgG: r = 0.74, p = 0.0001). The CD4+ T cells at Days 8 and 21 expanded after prime vaccination and this expansion correlated strongly with early post-vaccination HAI and Neut titers (p ≤ 0.002). In an adult population, the rapid serological response observed after initial H3N2v vaccination correlates with post-vaccination plasmablasts and CD4+ T cell responses.
