Profiles of influenza A/H1N1 vaccine response using hemagglutination-inhibition titers

Abstract

To identify distinct antibody profiles among adults 50-to-74 years old using influenza A/H1N1 HI titers up to 75 days after vaccination. Healthy subjects 50 to 74 years old received the 2010-2011 trivalent inactivated influenza vaccine. We measured venous samples from Days 0, 28, and 75 for HI and VNA and B-cell ELISPOTs. Of 106 subjects, HI titers demonstrated a ceiling effect for 11 or 10% for those with a pre-vaccination HI titer of 1:640 where no subject post-vaccination had an increase in titer. Of the remaining 95 subjects, only 37 or 35% overall had at least a 4-fold increase by Day 28. Of these 37, 3 waned at least 4-fold, and 13 others 2-fold. Thus 15% of the subjects showed waning antibody titers by Day 75. More than half failed to respond at all. The profiles populated by these subjects as defined by HI did not vary with age or gender. The VNA results mimicked the HI profiles, but the profiles for B-cell ELISPOT did not. HI titers at Days 0, 28, and 75 populate 4 biologically plausible profiles. Limitations include lack of consensus for operationally defining waning as well as for the apparent ceiling. Furthermore, though well accepted as a marker for vaccine response, assigning thresholds with HI has limitations. However, VNA closely matches HI in populating these profiles. Thus, we hold that these profiles, having face- and content-validity, may provide a basis for understanding variation in genomic and transcriptomic response to influenza vaccination in this age group.

Keywords:

• aging
• antibodies
• hemagglutinin glycoproteins
• hemagglutination inhibition tests
• H1N1 subtype
• influenza vaccines
• influenza a virus
• influenza virus
• viral

Abbreviations:

• ASC, Antibody-Secreting Cells
• ELISPOT, Enzyme-Linked ImmunoSpot
• Et al., Et alia (and others)
• HI, Hemagglutination-Inhibition
• IgG, Immunoglobulin G
• IQR, Interquartile Range
• MDCK, Madin-Darby Canine Kidney
• μl, Microliters
• p, p-value
• PFU, Plaque-Forming Units
• RBC, Red Blood Cells
• TCID50, Tissue Culture Infectious Dose 50
• VNA, Virus Neutralization Assay
• WHO, World Health Organization

Disclosure of Potential Conflicts of Interest

Dr. Poland is the chair of a safety evaluation committee for novel investigational vaccine trials being conducted by Merck Research Laboratories. Dr. Poland offers consultative advice on vaccine development to Merck & Co. Inc.., CSL Biotherapies, Avianax, Sanofi Pasteur, Dynavax, Novartis Vaccines and Therapeutics, PAXVAX Inc., Emergent Biosolutions, Vaxness, and Adjuvance. Dr. Jacobson serves as a member on a safety review committee and on a data monitoring committee concerning several non-influenza vaccines in studies funded by Merck Research Laboratories. These activities have been reviewed by the Mayo Clinic Conflict of Interest Review Board and are conducted in compliance with Mayo Clinic Conflict of Interest policies. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and was conducted in compliance with Mayo Clinic Conflict of Interest policies.

Acknowledgments

We would like to acknowledge the work of Krista Goergen who served as our statistical programmer analyst in this effort. We would also like to thank our patients who volunteered to participate in our study.

Funding

This study was funded by the National Institute of Allergic and Infectious Diseases of the National Institutes of Health (Bioinformatics Approach to Influenza A/H1N1 Vaccine Immune Profiling, HIPC, U01 AI 089859). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.