Redefining non-inferiority in anamnestic antibody responses using the mean increase of log-transformed antibody titers after revaccination: secondary analysis of a randomized controlled rabies vaccination trial

Lisanne A. Overduin, Patrick H. P. Soentjens, Jelle J. Goeman, Magdalena A. Berkowska, Jacques J. M. van Dongen, Leo G. Visser

Research output: Contribution to journalA1: Web of Science-article

Abstract

Non-inferiority in the anamnestic antibody response is conventionally determined by comparing seroconversion rates after revaccination. However, this approach is inadequate in the case of high pre-booster antibody titers. Therefore, we propose an alternative method to determine non-inferiority of booster responses. We used anonymized data from a randomized controlled trial (NCT01388985; EudraCT 2011-001612-62) in 500 adults, comparing a two-visit primary vaccination schedule (two intradermal 0.1 mL rabies vaccine doses on day 0 and 7) with a three-visit schedule (single intradermal 0.1 mL dose on day 0, 7, and 28). Participants were revaccinated intradermally (single dose) 1 to 3 years later. Rabies virus neutralizing antibody titers were measured on day 0 and 7 after revaccination. After log(3)-transformation of antibody titers, the mean increase in titers after revaccination was compared between schedules. Non-inferiority was defined as the lower bound of the two-sided 95% confidence interval not exceeding -0.369. Four hundred and ten participants fulfilled the inclusion criteria. The mean increase in log(3) titer was 2.21 and 2.31 for the two-visit and three-visit schedule, respectively. The difference between these increases was -0.10 [-0.28, 0.08], meeting the non-inferiority criterion. In conclusion, comparing mean increases in log-transformed titers after revaccination appears to be a feasible and more informative method of studying non-inferiority regarding the anamnestic antibody response.

Original languageEnglish
Article number721
JournalVaccines
Volume8
Issue number4
Number of pages11
ISSN2076-393X
DOIs
Publication statusPublished - 2020

Keywords

  • rabies vaccines
  • neutralizing antibodies
  • revaccination
  • boostability
  • immunogenicity
  • immunologic memory
  • pre-exposure vaccination
  • non-inferiority
  • intradermal injection
  • STATISTICS NOTES
  • COST

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