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

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.

SUBMITTER: Esser ES

PROVIDER: S-EPMC5515933 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Enhancing humoral immunity via sustained-release implantable microneedle patch vaccination.

Project description:Sustained exposure of lymphoid tissues to vaccine antigens promotes humoral immunity, but traditional bolus immunizations lead to rapid antigen clearance. We describe a technology to tailor vaccine kinetics in a needle-free platform translatable to human immunization. Solid pyramidal microneedle (MN) arrays were fabricated with silk fibroin protein tips encapsulating a stabilized HIV envelope trimer immunogen and adjuvant, supported on a dissolving polymer base. Upon brief skin application, vaccine-loaded silk tips are implanted in the epidermis/upper dermis where they release vaccine over a time period determined by the crystallinity of the silk matrix. Following MN immunization in mice, Env trimer was released over 2 wk in the skin, correlating with increased germinal center (GC) B cell responses, a ∼1,300-fold increase in serum IgG titers and a 16-fold increase in bone marrow (BM) plasma cells compared with bolus immunization. Thus, implantable MNs provide a practical means to substantially enhance humoral immunity to subunit vaccines.

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Transgenerational priming of immunity: maternal exposure to a bacterial antigen enhances offspring humoral immunity.

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| S-EPMC7044469 | biostudies-literature

Pre-conception maternal helminth infection transfers via nursing long-lasting cellular immunity against helminths to offspring.

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| S-EPMC6587632 | biostudies-literature

Microneedle patch tattoos

Project description:Summary Medical tattoos provide medical information, guide radiotherapy, and improve cosmetic outcomes of medical interventions. These tattoos are administered by repeated needle injection that causes pain, bleeding, and risk of infection, which limit more widespread use. Here, we developed single-use microneedle (MN) patches to deposit tattoos in the skin in a simple, rapid, painless, and bloodless way without biohazardous sharps waste. MN patch tattoos were designed with numbers, letters, symbols, environmentally responsive inks, and QR codes. Colored tattoos, and tattoos only visible with ultraviolet illumination for increased privacy, were developed and retained in the skin for at least one year. These MN patch tattoos recorded medical conditions such as diabetic medical alerts and vaccination status, responded to biophysical cues for possible physiological monitoring, and encoded complex personal health information. MN patches may increase safety and access to medical tattoos for improved fiducial marking, medical information storage, physiological monitoring, and cosmetic outcomes. Graphical abstract Highlights • Microneedle patches tattoo skin in a simple, rapid, painless, and bloodless way• Microneedle patches facilitate medical, veterinary, and cosmetic tattooing• Medical tattoos communicate health status and store information in a patient’s skin Medical device; Medical biotechnology; Biomaterials

| S-EPMC9617462 | biostudies-literature

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| S-EPMC3696570 | biostudies-other

Long-term protective immunity from an influenza virus-like particle vaccine administered with a microneedle patch.

Project description:Skin vaccination with influenza virus-like particles (VLPs) using microneedles has been shown to induce protection similar to or better than that induced by intramuscular immunization. In this study, we examined the long-term protective efficacy of influenza (H1N1 A/PR/8/34) VLPs after skin vaccination using microneedle patches coated with the vaccine. Microneedle vaccination of mice in the skin induced 100% protection against lethal challenge infection with influenza A/PR/8/34 virus 14 months after a single vaccine dose. Influenza virus-specific total IgG response and hemagglutination inhibition (HAI) titers were maintained at high levels for over 1 year after microneedle vaccination. Microneedle vaccination also induced substantial levels of lung IgG and IgA antibody responses, and antibody-secreting plasma cells from spleen and bone marrow, as well as conferring effective control of lung viral loads, resulting in complete protection 14 months after vaccination. These strong and long-lasting immune responses were enabled in part by stabilization of the vaccine by formulation with trehalose during microneedle patch fabrication. Administration of the stabilized vaccine using microneedles was especially effective at enabling strong recall responses measured 4 days after lethal virus challenge, including increased HAI and antibody-secreting cells in the spleen and reduced viral titer and inflammatory response in the lung. The results in this study indicate that skin vaccination with VLP vaccine using a microneedle patch provides long-term protection against influenza in mice.

| S-EPMC3889580 | biostudies-literature

Feasibility of Hepatitis B Vaccination by Microneedle Patch: Cellular and Humoral Immunity Studies in Rhesus Macaques.

Project description:BackgroundThis study evaluated dissolvable microneedle patch (dMNP) delivery of hepatitis B vaccine in rhesus macaques and provides evidence that dMNP delivery elicits seroprotective anti-HBs levels comparable with human seroprotection, potentially useful for hepatitis B birth dose vaccination in resource-constrained regions.MethodsSixteen macaques were each vaccinated twice; they were treated in 4 groups, with dMNP delivery of AFV at 24 ± 8 µg (n = 4) or 48 ± 14 µg (n = 4), intramuscular injection of AFV (10 µg; n = 4), or intramuscular injection of AAV (10 µg; n = 4). Levels of antibody to hepatitis B surface antigen (HBsAg) (anti-HBs) and HBsAg-specific T-cell responses were analyzed.ResultsSix of 8 animals with dMNP delivery of AFV had anti-HBs levels ≥10 mIU/mL after the first vaccine dose. After dMNP delivery of AFV, interferon γ, interleukin 2, and interleukin 4 production by HBsAg-specific T cells was detected. A statistically significant positive correlation was detected between anti-HBs levels and cells producing HBsAg-specific interferon γ and interleukin 2 (T-helper 1-type cytokine) and interleukin 4 (T-helper 2-type cytokine) in all anti-HBs-positive animals.ConclusionsdMNP delivery of AFV can elicit seroprotective anti-HBs levels in rhesus macaques that are correlated with human seroprotection, and it could be particularly promising for birth dose delivery of hepatitis B vaccine in resource-constrained regions.

| S-EPMC6834072 | biostudies-literature

Maternal diet in pregnancy and offspring blood pressure.

Project description:Associations between maternal nutrient intakes in late pregnancy and offspring blood pressure at 7(1/2) years were investigated in 6944 singletons from the Avon Longitudinal Study of Parents and Children. The only finding was a weak inverse association with omega-3 fatty acids that was lost after adjustment for potential confounders, suggesting that diet in pregnancy does not influence offspring blood pressure in well-nourished populations.

| S-EPMC1720401 | biostudies-literature

Maternal Hyperglycemia during Pregnancy Increases Adiposity of Offspring.

Project description:BackgroundThe effect of intrauterine hyperglycemia on fat mass and regional fat proportion of the offspring of mothers with gestational diabetes mellitus (OGDM) remains to be determined.MethodsThe body composition of OGDM (n=25) and offspring of normoglycemic mothers (n=49) was compared using dualenergy X-ray absorptiometry at age 5 years. The relationship between maternal glucose concentration during a 100 g oral glucose tolerance test (OGTT) and regional fat mass or proportion was analyzed after adjusting for maternal prepregnancy body mass index (BMI).ResultsBMI was comparable between OGDM and control (median, 16.0 kg/m2 vs. 16.1 kg/m2 ). Total, truncal, and leg fat mass were higher in OGDM compared with control (3,769 g vs. 2,245 g, P=0.004; 1,289 g vs. 870 g, P=0.017; 1,638 g vs. 961 g, P=0.002, respectively), whereas total lean mass was lower in OGDM (15,688 g vs. 16,941 g, P=0.001). Among OGDM, total and truncal fat mass were correlated with fasting and 3-hour glucose concentrations of maternal 100 g OGTT during pregnancy (total fat mass, r=0.49, P=0.018 [fasting], r=0.473, P=0.023 [3-hour]; truncal fat mass, r=0.571, P=0.004 [fasting], r=0.558, P=0.006 [3-hour]), but there was no correlation between OGDM leg fat mass and maternal OGTT during pregnancy. Regional fat indices were not correlated with concurrent maternal 75 g OGTT values.ConclusionIntrauterine hyperglycemia is associated with increased fat mass, especially truncal fat, in OGDM aged 5 years.

| S-EPMC8497931 | biostudies-literature

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