Journal of Clinical Immunology

, Volume 34, Issue 6, pp 655–662

High Level Antibody Avidity is Achieved in HIV-Seropositive Recipients of an Inactivated Split Adjuvanted (AS03A) Influenza Vaccine

  • Karen K. Yam
  • Erica Gipson
  • Marina Klein
  • Sharon Walmsley
  • David Haase
  • Scott Halperin
  • David Scheifele
  • Brian J. Ward
  • Curtis Cooper
Original Research

Abstract

Purpose

More severe influenza disease and poor vaccine immunogenicity is reported in HIV-infected patients. We measured antibody avidity after influenza vaccination in HIV patients to assess vaccine efficacy.

Methods

Two dosing strategies (Group1: single dose, n = 28. Group2: single dose plus booster, n = 36) with an AS03A-adjuvanted H1N12009 pandemic influenza vaccine (Arepanrix, GSK) were assessed in HIV patients. Serum hemagglutination inhibition (HAI) titers and antibody avidity reported as an avidity index (AI) were measured at days 21 and 42 and at 6 months.

Results

Baseline HIV parameters were similar among all participants. Eighteen participants had measurable baseline HAI titers. In these subjects, AI was at ~9 at baseline and was not significantly increased by one or two vaccine doses. In those without detectable baseline antibodies, immunization induced modest antibody titers [Group1 HAI, 61 (26–144); Group2 HAI, 46 (28–76)] with high AI after one dose at day 21 [Group1 AI, 8.8 (7.3–10.7); Group2 AI, 8.9 (7.8–10.1)]. A second dose of vaccine generated significantly higher HAI titers at day 42 [Group1 HAI, 41 (18–90); Group2 HAI, 92 (64–132)] and persisted to 6 months [Group1 HAI, 9 (6–13); Group2 HAI, 19 (13–30)]. All subjects who produced detectable HAI titers after vaccination generated high antibody avidity (AI, 9–10), which persisted up to 6 months.

Conclusion

In participants initially seronegative, two doses of vaccine enabled a greater percentage of subjects to respond to the vaccine and elicited higher HAI titers. All subjects who produced detectable HAI titers also rapidly generated high AI in the short and long term. We demonstrate that high avidity antibodies can be achieved after vaccination and support a two-dose immunization strategy for HIV-positive subjects.

Keywords

Adjuvant HIV influenza vaccine antibody avidity 

Supplementary material

10875_2014_54_Fig2_ESM.gif (63 kb)
Supplemental Figure 1

Antibody responses in HIV-infected patients immunized with one or two doses of AS03-adjuvanted pdmH1N1 split vaccine as a function of the degree of HIV RNA suppression. Subjects in Group 1 received the priming immunization only (day 0), while subjects in group 2 received prime (day 0) and booster immunization (day 21). Serum was collected at baseline on day 0, and following immunizations on day 21, 42 and 180. The HAI titers were previously determined and adapted from [12] and the avidity index (AI) was determined by ELISA. HAI titer (a, c, e) and antibody avidity (b, d, f) as a function of the degree of HIV RNA suppression. Individual subjects and geometric means are shown. Gp 1, group 1; Gp, 2, group 2. D, detectable viremia; S, HIV RNA suppressed below the lower limit of detection. (GIF 63 kb)

10875_2014_54_MOESM1_ESM.tif (1.2 mb)
High resolution image (TIFF 1206 kb)
10875_2014_54_Fig3_ESM.gif (73 kb)
Supplemental Figure 2

Antibody responses in HIV-infected patients immunized with one or two doses of AS03-adjuvanted pdmH1N1 split vaccine as a function of ARV use. Subjects in Group 1 received the priming immunization only (day 0), while subjects in group 2 received prime (day 0) and booster immunization (day 21). Serum was collected at baseline on day 0, and following immunizations on day 21, 42 and 180. The HAI titers were previously determined and adapted from [12] and the avidity index (AI) was determined by ELISA. HAI titer (a, c, e) and antibody avidity (b, d, f) as a function of ARV use. Individual subjects and geometric means are shown. Gp 1, group 1; Gp, 2, group 2. D, detectable viremia; none, no ARV use; haart, on haart ARV therapy. (GIF 72 kb)

10875_2014_54_MOESM2_ESM.tif (1.3 mb)
High resolution image (TIFF 1308 kb)
10875_2014_54_Fig4_ESM.gif (15 kb)
Supplemental Figure 3

CD4 T-lymphocyte count. Subjects in Group 1 received the priming immunization only (day 0), while subjects in group 2 received prime (day 0) and booster immunization (day 21). Individual subjects and geometric means with 95 % confidence intervals are shown. Gp 1, group 1; Gp, 2, group 2. (GIF 15 kb)

10875_2014_54_MOESM3_ESM.tif (245 kb)
High resolution image (TIFF 244 kb)

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Karen K. Yam
    • 1
  • Erica Gipson
    • 1
  • Marina Klein
    • 2
  • Sharon Walmsley
    • 3
  • David Haase
    • 4
  • Scott Halperin
    • 4
  • David Scheifele
    • 5
  • Brian J. Ward
    • 1
    • 6
  • Curtis Cooper
    • 7
  1. 1.Department of Experimental MedicineResearch Institute of the McGill University Health CentreMontrealCanada
  2. 2.McGill UniversityMontrealCanada
  3. 3.University of TorontoTorontoCanada
  4. 4.Dalhousie UniversityHalifaxCanada
  5. 5.University of British ColumbiaVancouverCanada
  6. 6.Vaccine Study Centre, Research Institute of the McGill University Health CentreMontrealCanada
  7. 7.University of Ottawa Division of Infectious DiseasesThe Ottawa Hospital Research Institute-General CampusOttawaCanada

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