Microneedle patch delivery of influenza vaccine during pregnancy enhances maternal immune responses promoting survival and long-lasting passive immunity to offspring

Sci Rep. 2017 Jul 18;7(1):5705. doi: 10.1038/s41598-017-05940-7.

Abstract

Influenza virus causes life-threatening infections in pregnant women and their newborns. Immunization during pregnancy is the most effective means of preventing maternal and infant mortality/morbidity; however, influenza vaccination rates of pregnant women remain under 50%. Furthermore, the availability of vaccines in low-resource populations is limited. Skin immunization with microneedle patches (MN) is a novel and safe vaccination platform featuring thermostable vaccine formulations. Cold-chain independence and the potential for self-administration can expand influenza vaccination coverage in developing countries. In this study of pregnant BALB/c mice immunized with subunit H1N1 influenza vaccine, we demonstrate the advantage of skin vaccination over intramuscular delivery of a two-fold higher vaccine dose. MN vaccine induced superior humoral immune responses and conferred protective immunity against a lethal challenge dose of homologous influenza virus. Importantly, MN vaccination of mice at mid-gestation resulted in enhanced and long-lasting passive immunity of the offspring, measured by neutralizing antibody titers and survival rates after virus challenge. We conclude that skin vaccination using MN is a superior immunization approach with the potential to overcome immune tolerance observed in pregnancy, and lower vaccination costs through antigen dose-sparing, which is especially relevant in underserved countries.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Cutaneous*
  • Animals
  • Antibodies, Viral
  • Drug Delivery Systems*
  • Female
  • Immunity, Humoral
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / immunology*
  • Male
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control
  • Pregnancy
  • Survival Analysis
  • Vaccination / methods*
  • Viral Vaccines / administration & dosage*

Substances

  • Antibodies, Viral
  • Influenza Vaccines
  • Viral Vaccines