Tetanus vaccination with a dissolving microneedle patch confers protective immune responses in pregnancy.
Maternal and neonatal tetanus claim tens of thousands lives every year in developing countries, but could be prevented by hygienic practices and improved immunization of pregnant women. This study tested the hypothesis that skin vaccination can overcome the immunologically transformed state of pregnancy and enhance protective immunity to tetanus in mothers and their newborns. To achieve this goal, we developed microneedle patches (MNPs) that efficiently delivered unadjuvanted tetanus toxoid to skin of pregnant mice and demonstrated that this route induced superior immune responses in female mice conferring 100% survival to tetanus toxin challenge when compared to intramuscular vaccination. Mice born to MNP-vaccinated mothers showed detectable tetanus-specific IgG antibodies up to 12weeks of age and complete protection to tetanus toxin challenge up at 6weeks of age. In contrast, none of the 6-week old mice born to intramuscularly vaccinated mothers survived challenge. Although pregnant mice vaccinated with unadjuvanted tetanus toxoid had 30% lower IgG and IgG1 titers than mice vaccinated intramuscularly with Alum®-adjuvanted tetanus toxoid vaccine, IgG2a titers and antibody affinity maturation were similar between these groups. We conclude that skin immunization with MNPs containing unadjuvanted tetanus toxoid can confer potent protective efficacy to mothers and their offspring using a delivery method well suited for expanding vaccination coverage in developing countries.
Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta 30322, Georgia.
E Stein
ES
Esser
School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta 30332, Georgia.
AndreyA
A
Romanyuk
Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta 30322, Georgia.
Elena V
EV
Vassilieva
Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta 30322, Georgia.
Joshy
J
Jacob
School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta 30332, Georgia.
Mark R
MR
Prausnitz
Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta 30322, Georgia.
Richard W
RW
Compans
Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta 30322, Georgia. Electronic address: iskount@emory.edu.
Ioanna
I
Skountzou
D000818:Animals; D004337:Drug Carriers; D065546:Drug Liberation; D005260:Female; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D007928:Lethal Dose 50; D051379:Mice; D008807:Mice, Inbred BALB C; D009339:Needles; D010316:Particle Size; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology / Q000517:prevention & control*; D013499:Surface Properties; D013742:Tetanus / Q000276:immunology / Q000517:prevention & control*; D013745:Tetanus Toxoid / Q000008:administration & dosage* / Q000276:immunology; D057968:Transdermal Patch; D014611:Vaccination
D004337:Drug Carriers; D007074:Immunoglobulin G; D013745:Tetanus Toxoid
Dissolving microneedle patches; Mouse model; Pregnancy; Skin immunization; Survival; Tetanus toxoid