Solid bioneedle-delivered influenza vaccines are highly thermostable and induce both humoral and cellular immune responses

PLoS One. 2014 Mar 26;9(3):e92806. doi: 10.1371/journal.pone.0092806. eCollection 2014.

Abstract

The potential of bioneedles to deliver influenza vaccines was investigated. Four influenza vaccine formulations were screened to determine the optimal formulation for use with bioneedles. The stability of the formulations after freeze-drying was checked to predict the stability of the influenza vaccines in the bioneedles. Subunit, split, virosomal and whole inactivated influenza (WIV) vaccine were formulated and lyophilized in bioneedles, and subsequently administered to C57BL/6 mice. Humoral and cellular immune responses were assessed after vaccination. The thermostability of lyophilized vaccines was determined after one-month storage at elevated temperatures. Bioneedle influenza vaccines induced HI titers that are comparable to those induced by intramuscular WIV vaccination. Delivery by bioneedles did not alter the type of immune response induced by the influenza vaccines. Stability studies showed that lyophilized influenza vaccines have superior thermostability compared to conventional liquid vaccines, and remained stable after one-month storage at 60°C. Influenza vaccines delivered by bioneedles are a viable alternative to conventional liquid influenza vaccines. WIV was determined to be the most potent vaccine formulation for administration by bioneedles. Lyophilized influenza vaccines in bioneedles are independent of a cold-chain, due to their increased thermostability, which makes distribution and stockpiling easier.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Viral / immunology
  • Cell Count
  • Freeze Drying
  • Hemagglutination Inhibition Tests
  • Immunity, Cellular / immunology*
  • Immunity, Humoral / immunology*
  • Immunization, Secondary
  • Immunoglobulin G / blood
  • Influenza Vaccines / immunology*
  • Interferon-gamma / biosynthesis
  • Interleukin-4 / biosynthesis
  • Mice, Inbred C57BL
  • Needles*
  • Spleen / pathology
  • Temperature*
  • Vaccination

Substances

  • Antigens, Viral
  • Immunoglobulin G
  • Influenza Vaccines
  • Interleukin-4
  • Interferon-gamma

Grant support

This work was funded by the Dutch Ministry of Health, Welfare and Sport. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.