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Nitesh K Kunda, Dominique N Price, Pavan Muttil
Pulmonary delivery of drugs and vaccines is an established route of administration, with particulate-based carriers becoming an attractive strategy to enhance the benefits of pulmonary therapeutic delivery. Despite the increasing number of publications using the pulmonary route of delivery, the lack of effective and uniform administration techniques in preclinical models generally results in poor translational success. In this study, we used the IVIS Spectrum small-animal in vivo imaging system to compare the respiratory tract deposition and distribution pattern of a microsphere suspension (5 µm) in mice after 1, 4, and 24 h when delivered by oropharyngeal aspiration, the Microsprayer® Aerosolizer, and the BioLite Intubation System, three-widely reported preclinical inhalation techniques...
July 10, 2018: Vaccines
Xiaofang Xiong, Jugal Kishor Das, Jianyong Song, Bing Ni, Xingcong Ren, Jin-Ming Yang, Jianxun Song
Hematopoietic stem cells (HSCs) yield both the myeloid and lymphoid lineages of blood cells and can be reprogrammed into tumor antigen (Ag)-specific CD8⁺ cytotoxic T lymphocytes (CTLs) to prevent tumor growth. However, the optimal approach for differentiating tumor Ag-specific CTLs from HSCs, such as HSC-CTLs, remains elusive. In the current study, we showed that a combination of genetic modification of HSCs and in vivo T cell development facilitates the generation of Ag-specific CTLs that suppressed tumor growth...
July 6, 2018: Vaccines
Ewan P Plant, Angelia A Eick-Cost, Hussein Ezzeldin, Jose L Sanchez, Zhiping Ye, Michael J Cooper
The first exposure to influenza is thought to impact subsequent immune responses later in life. The consequences of this can be seen during influenza epidemics and pandemics with differences in morbidity and mortality for different birth cohorts. There is a need for better understanding of how vaccine responses are affected by early exposures to influenza viruses. In this analysis of hemagglutination inhibition (HI) antibody responses in two cohorts of military personnel we noticed differences related to age, sex, prior vaccination, deployment and birth year...
July 3, 2018: Vaccines
Romain Paillot, Dion Garrett, Maria R Lopez-Alvarez, Ihlan Birand, Fernando Montesso, Linda Horspool
Vaccination is one of the most effective tools for limiting the impact of equine influenza (EI). The humoral immunity established following a primary vaccination course can decrease significantly between the second (V2) and third immunisations (V3), leaving some horses insufficiently protected for several weeks. This so-called "immunity gap" poses a challenge to all EI vaccines. During this period, the EI infection of vaccinated animals may be followed by marked clinical signs and virus shedding. However, several EI vaccines have been shown to stimulate equine influenza virus (EIV)-specific cell-mediated immunity, which is likely to play a role in protection against EIV infection and/or mitigate the clinical and virological signs of EI...
July 2, 2018: Vaccines
Mona O Mohsen, Ariane C Gomes, Monique Vogel, Martin F Bachmann
Virus-like particles (VLPs) derived from viral nucleocapsids are an important class of nanoparticles. The structure, uniformity, stability, and function of these VLPs have attracted scientists in utilizing them as a unique tool in various applications in biomedical fields. Their interaction with the innate immune system is of major importance for the adaptive immune response they induce. The innate immune cells and molecules recognize and interact with VLPs on the basis of two major characteristics: size and surface geometry...
July 2, 2018: Vaccines
Natalie K Thulin, Taia T Wang
Recent studies have revealed multiple roles for Fc gamma receptors (FcγRs) in broad immunity against influenza viruses. Activating FcγR pathways can be harnessed to confer protection mediated by non-neutralizing anti-HA IgGs and to increase the potency of broadly neutralizing anti-HA IgGs and of anti-NA IgGs. Separate FcγR pathways can be targeted to enhance the breadth of antibody responses elicited by seasonal influenza virus vaccines. Here, we review the current understanding of FcγR pathways in broad influenza immunity and suggest mechanisms to bypass FcγR signaling heterogeneity among people that arises from distinctions in structural repertoires of IgG Fc domains...
June 29, 2018: Vaccines
Tatsuya Yamazaki, Joe Chiba, Sachiko Akashi-Takamura
Hemagglutinin (HA) of influenza virus is a major target for vaccines. HA initiates the internalization of the virus into the host cell by binding to host sialic acid receptors; therefore, inhibition of HA can significantly prevent influenza virus infection. However, the high diversity of HA permits the influenza virus to escape from host immunity. Moreover, the vaccine efficacy is poor in some high-risk populations (e.g., elderly or immunocompromised patients). Passive immunization with anti-HA monoclonal antibodies (mAbs) is an attractive therapy; however, this method has high production costs and requires repeated inoculations...
June 26, 2018: Vaccines
Sílvia A Sousa, António M M Seixas, Jorge H Leitão
Bacteria of the Burkholderia cepacia complex (Bcc) remain an important cause of morbidity and mortality among patients suffering from cystic fibrosis. Eradication of these pathogens by antimicrobial therapy often fails, highlighting the need to develop novel strategies to eradicate infections. Vaccines are attractive since they can confer protection to particularly vulnerable patients, as is the case of cystic fibrosis patients. Several studies have identified specific virulence factors and proteins as potential subunit vaccine candidates...
June 8, 2018: Vaccines
Jonathan W Yewdell
Like every MD Ph.D. pup, I was faced with the BIG decision: medicine or science?[...].
May 31, 2018: Vaccines
Kristin G-I Mohn, Fan Zhou
The influenza virus is one of a few viruses that is capable of rendering an otherwise healthy person acutly bedridden for several days. This impressive knock-out effect, without prodromal symptoms, challenges our immune system. The influenza virus undergoes continuous mutations, escaping our pre-existing immunity and causing epidemics, and its segmented genome is subject to reassortment, resulting in novel viruses with pandemic potential. The personal and socieoeconomic burden from influenza is high. Vaccination is the most cost-effective countermeasure, with several vaccines that are available...
May 26, 2018: Vaccines
John R Gallagher, Dustin M McCraw, Udana Torian, Neetu M Gulati, Mallory L Myers, Michael T Conlon, Audray K Harris
Influenza viruses affect millions of people worldwide on an annual basis. Although vaccines are available, influenza still causes significant human mortality and morbidity. Vaccines target the major influenza surface glycoprotein hemagglutinin (HA). However, circulating HA subtypes undergo continual variation in their dominant epitopes, requiring vaccines to be updated annually. A goal of next-generation influenza vaccine research is to produce broader protective immunity against the different types, subtypes, and strains of influenza viruses...
May 25, 2018: Vaccines
Sasha E Larsen, Susan L Baldwin, Mark T Orr, Valerie A Reese, Tiffany Pecor, Brian Granger, Natasha Dubois Cauwelaert, Brendan K Podell, Rhea N Coler
It is estimated that one third of the world's population is infected with Mycobacterium tuberculosis ( Mtb ). This astounding statistic, in combination with costly and lengthy treatment regimens make the development of therapeutic vaccines paramount for controlling the global burden of tuberculosis. Unlike prophylactic vaccination, therapeutic immunization relies on the natural pulmonary infection with Mtb as the mucosal prime that directs boost responses back to the lung. The purpose of this work was to determine the protection and safety profile over time following therapeutic administration of our lead Mtb vaccine candidate, ID93 with a synthetic TLR4 agonist (glucopyranosyl lipid adjuvant in a stable emulsion (GLA-SE)), in combination with rifampicin, isoniazid, and pyrazinamide (RHZ) drug treatment...
May 24, 2018: Vaccines
Sarah Sebastian, Teresa Lambe
Influenza-virus-mediated disease can be associated with high levels of morbidity and mortality, particularly in younger children and older adults. Vaccination is the primary intervention used to curb influenza virus infection, and the WHO recommends immunization for at-risk individuals to mitigate disease. Unfortunately, influenza vaccine composition needs to be updated annually due to antigenic shift and drift in the viral immunogen hemagglutinin (HA). There are a number of alternate vaccination strategies in current development which may circumvent the need for annual re-vaccination, including new platform technologies such as viral-vectored vaccines...
May 24, 2018: Vaccines
Joseph A Lewnard, Sarah Cobey
The imperfect effectiveness of seasonal influenza vaccines is often blamed on antigenic mismatch, but even when the match appears good, effectiveness can be surprisingly low. Seasonal influenza vaccines also stand out for their variable effectiveness by age group from year to year and by recent vaccination status. These patterns suggest a role for immune history in influenza vaccine effectiveness, but inference is complicated by uncertainty about the contributions of bias to the estimates themselves. In this review, we describe unexpected patterns in the effectiveness of seasonal influenza vaccination and explain how these patterns might arise as consequences of study design, the dynamics of immune memory, or both...
May 21, 2018: Vaccines
Sinthujan Jegaskanda
Despite global vaccination efforts, influenza virus continues to cause yearly epidemics and periodic pandemics throughout most of the world. Many of us consider the generation of broader, potent and long-lasting immunity against influenza viruses as critical in curtailing the global health and economic impact that influenza currently plays. To date, classical vaccinology has relied on the generation of neutralizing antibodies as the benchmark to measure vaccine effectiveness. However, recent developments in numerous related fields of biomedical research including, HIV, HSV and DENV have emphasized the importance of Fc-mediate effector functions in pathogenesis and immunity...
May 17, 2018: Vaccines
Luis Vitetta, Emma Tali Saltzman, Michael Thomsen, Tessa Nikov, Sean Hall
The authors wish to make the following corrections to this paper due to a typesetting error in the conclusion of this article which was recently published in Vaccines.
May 15, 2018: Vaccines
John D Mooney, Michael Imarhiagbe, Jonathan Ling
A recently reported steep increase in the incidence of invasive pneumococcal disease (IPD) in adults in the North East of England was primarily associated with pneumococcal sero-types found in the 23-valent pneumococcal polysaccharide vaccine (PPSV23). This region also has one of the highest rates of alcohol-related premature mortality and morbidity in the UK. Given that alcohol dependence is long acknowledged as one of the strongest risk factors for IPD mortality, we feel there is an increasingly compelling case to look again at the divergence of UK vaccine guidance from that of the World Health Organisation and the Centre for Disease Control in the USA, in the non-inclusion of alcoholism as an indicator condition that would potentially benefit from receiving PPSV23 vaccine...
May 2, 2018: Vaccines
Surender Khurana
Vaccination against influenza is the most effective approach for reducing influenza morbidity and mortality. However, influenza vaccines are unique among all licensed vaccines as they are updated and administered annually to antigenically match the vaccine strains and currently circulating influenza strains. Vaccine efficacy of each selected influenza virus vaccine varies depending on the antigenic match between circulating strains and vaccine strains, as well as the age and health status of the vaccine recipient...
April 27, 2018: Vaccines
Hannah D Stacey, Neda Barjesteh, Jonathan P Mapletoft, Matthew S Miller
Vaccination against the seasonal influenza virus is the best way to prevent infection. Nevertheless, vaccine efficacy remains far from optimal especially in high-risk populations such as the elderly. Recent technological advancements have facilitated rapid and precise identification of the B and T cell epitopes that are targets for protective responses. While these discoveries have undoubtedly brought the field closer to "universal" influenza virus vaccines, choosing the correct antigen is only one piece of the equation...
April 12, 2018: Vaccines
Yemesrach A Tefera, Abram L Wagner, Eyoel B Mekonen, Bradley F Carlson, Matthew L Boulton
Predictors of immunization status outside of large cities in Ethiopia are not well known, and Muslims have lower vaccination coverage. The aim of this study is to assess factors associated with full immunization among children 12-23 months in Worabe, Ethiopia, a Muslim-majority community. A cross-sectional study is conducted in summer 2016. Multivariable logistic regression was used to assess the significance of predictors of full immunization. Among 484 children, 61% are fully vaccinated. Children whose mothers had fewer antenatal care (ANC) visits have decreased odds of full vaccination (zero visits: odds ratio (OR) = 0...
April 10, 2018: Vaccines
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