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: ASC, Antibody-Secreting Cells; ELISPOT, Enzyme-Linked ImmunoSpot; Et al., Et alia (and others); H1N1 subtype; HI, Hemagglutination-Inhibition; IQR, Interquartile Range; IgG, Immunoglobulin G; MDCK, Madin-Darby Canine Kidney; PFU, Plaque-Forming Units; RBC, Red Blood Cells; TCID50, Tissue Culture Infectious Dose 50; VNA, Virus Neutralization Assay; WHO, World Health Organization; aging; antibodies; hemagglutination inhibition tests; hemagglutinin glycoproteins; influenza a virus; influenza vaccines; influenza virus; p, p-value; viral; μl, Microliters.

Figure 1.

Algorithm of HI Results across the 106 Subjects by the Changes in Days 0, 28, and 75.

Figure 2.

Behavior of HI Titers across the 106 Subjects over Days 0, 28, and 75.

Figure 3.

Behavior of VNA Titers across the 106 Subjects over Days 0, 28, and 75.