Vaccine
-
Measles infection and vaccine response are complex biological processes that involve both viral and host genetic factors. We have previously investigated the influence of genetic polymorphisms on vaccine immune response, including measles vaccines, and have shown that polymorphisms in HLA, cytokine, cytokine receptor, and innate immune response genes are associated with variation in vaccine response but do not account for all of the inter-individual variance seen in vaccinated populations. In the current study we report the findings of a multigenic analysis of measles vaccine immunity, indicating a role for the measles virus receptor CD46, innate pattern-recognition receptors (DDX58, TLR2, 4, 5, 7 and 8) and intracellular signaling intermediates (MAP3K7, NFKBIA), and key antiviral molecules (VISA, OAS2, MX1, PKR) as well as cytokines (IFNA1, IL4, IL6, IL8, IL12B) and cytokine receptor genes (IL2RB, IL6R, IL8RA) in the genetic control of both humoral and cellular immune responses. This multivariate approach provided additional insights into the genetic control of measles vaccine responses over and above the information gained by our previous univariate SNP association analyses.
-
In fall 2010 in the southern hemisphere, an increased risk of febrile seizures was noted in young children in Australia in the 24 h after receipt of trivalent inactivated influenza vaccine (TIV) manufactured by CSL Biotherapies. Although the CSL TIV vaccine was not recommended for use in young children in the US, during the 2010-2011 influenza season near real-time surveillance was conducted for febrile seizures in the 0-1 days following first dose TIV in a cohort of 206,174 vaccinated children ages 6 through 59 months in the Vaccine Safety Datalink Project. On a weekly basis, surveillance was conducted with the primary approach of a self-controlled risk interval design and the secondary approach of a current vs. historical vaccinee design. ⋯ Risk difference estimates varied by age due to the varying baseline risk for seizures in young children, with the highest estimates occurring at 16 months (12.5 per 100,000 doses for TIV without concomitant PCV13, 13.7 per 100,000 doses for PCV13 without concomitant TIV, and 44.9 per 100,000 doses for concomitant TIV and PCV13) and the lowest estimates occurring at 59 months (1.1 per 100,000 doses for TIV without concomitant PCV13, 1.2 per 100,000 doses for PCV13 without concomitant TIV, and 4.0 per 100,000 doses for concomitant TIV and PCV13). Incidence rate ratio and risk difference estimates were lower for children receiving TIV without concomitant PCV13 or PCV13 without concomitant TIV. Because of the importance of preventing influenza and pneumococcal infections and associated complications, our findings should be placed in a benefit-risk framework to ensure that population health benefits are maximized.
-
Clinical Trial
Clinical study of transcutaneous vaccination using a hydrogel patch for tetanus and diphtheria.
Transcutaneous immunization (TCI) is a non-invasive and easy-to-use vaccination method. We demonstrated the efficacy and safety of a transcutaneous vaccine formulation using a hydrogel patch in animal experiments. In the present study, we performed a clinical study to apply our TCI formulation for vaccination against tetanus and diphtheria in human. ⋯ The amount of water and patch components in the stratum corneum increased after application of the TCI formulation, suggesting that the change in the skin condition was related to antigen penetration. These data indicate that this easy-to-use TCI system induces an immune response without severe adverse reactions in humans. This easy-to-use and safe TCI formulation enables mass treatment in an outbreak setting and increased vaccination rates in developing countries, and will greatly contribute to worldwide countermeasures against infectious diseases.
-
We analyzed humoral and cellular immune responses against vaccine antigens and the new A(H1N1) virus in healthy adults before and after immunization with the 2007/2008 commercially available trivalent subunit MF59-adjuvanted influenza vaccine during the Fall 2007, prior to the emergence of the new virus. Antibody titers were significantly boosted only against the three vaccine antigens. ⋯ The cross-reactivity of cellular responses might, at least in part, explain the low pathogenicity of the new pandemic virus. The finding of cellular immunity, that can be increased by seasonal vaccination, against the conserved HA peptide, underline the potential use, in human vaccines, of conserved peptides of the stalk region of HA characterized by broad immunogenicity in experimental systems.