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1.
Ann Clin Lab Sci ; 54(1): 118-120, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38514062

ABSTRACT

OBJECTIVE: We utilized Premier Hb9210 analyzer (HPLC method; Trinity Biotech, Jamestown, NY) for measuring HBA1c in whole blood. As our laboratory is transitioning to Abbott system, we compared HbA1c values obtained by Alinity c and Premier Hb9210. METHODS: The Premier Hb9210 analyzer is based on boronate affinity high performance liquid chromatography with analytical measurement range of 3.8 to 18.5%. The Alinity c Hemoglobin A1c assay measured both total hemoglobin and HbA1c (enzymatic assay) in whole blood and then calculated %HbA1c. The analytical measurement range of this assay is 4 to 14% of HbA1c. We evaluated the analytical performance of Alinity c HbA1c by evaluating precision and also comparing 77 clinical samples with our reference HPLC method. RESULTS: Both Alinity c HbA1c and Premier HB9210 have excellent total precision. Plotting HbA1c results obtained by the Premier Hb9210 analyzer in the x-axis (currently used reference method) and the corresponding values obtained by the Alinity c assay, we observed the following regression equation: y=0.9473x+0.1548 ( n=77, r=0.99). DISCUSSION: Our result indicates that HbA1c enzymatic assay on the Alinity c analyzer showed values comparable to HPLC method. However, at the decision points (2.8% average negative bias at >6.4% and 3.3% average negative bias at 7%), HbA1c values obtained by the Alinity c analyzer were lower than the reference method. CONCLUSIONS: We conclude that HbA1c assay on the Alinity c analyzer is a viable alternative to HPLC for measuring HbA1c in clinical laboratories but values at the decision points must be interpreted with caution and if necessary should be repeated by a reference HPLC method.


Subject(s)
Clinical Laboratory Services , Hematologic Tests , Humans , Glycated Hemoglobin , Chromatography, High Pressure Liquid , Immunoassay
2.
Vaccines (Basel) ; 12(2)2024 Jan 27.
Article in English | MEDLINE | ID: mdl-38400116

ABSTRACT

As new SARS-CoV-2 variants continue to emerge and impact communities worldwide, next-generation vaccines that enhance protective mucosal immunity may have a significant impact on productive infection and transmission. We have developed recombinant non-replicating adenovirus serotype 5 (rAd5) vaccines delivered by mucosal administration that express both target antigen and a novel molecular adjuvant within the same cell. Here, we describe the immunogenicity of three unique SARS-CoV-2 rAd5 vaccine candidates and their efficacy following viral challenge in non-human primates (NHPs). Intranasal immunization with rAd5 vaccines expressing Wuhan, or Beta variant spike alone, or Wuhan spike and nucleocapsid elicited strong antigen-specific serum IgG and IgA with neutralizing activity against multiple variants of concern (VOC). Robust cross-reactive mucosal IgA was detected after a single administration of rAd5, which showed strong neutralizing activity against multiple VOC. Additionally, mucosal rAd5 vaccination increased spike-specific IFN-γ producing circulating T-cells. Upon Beta variant SARS-CoV-2 challenge, all the vaccinated NHPs exhibited significant reductions in viral load and infectious particle shedding in both the nasal passages and lower airways. These findings demonstrate that mucosal rAd5 immunization is highly immunogenic, confers protective cross-reactive antibody responses in the circulation and mucosa, and reduces viral load and shedding after SARS-CoV-2 challenge.

3.
Microbiol Spectr ; 11(6): e0471722, 2023 Dec 12.
Article in English | MEDLINE | ID: mdl-37882564

ABSTRACT

IMPORTANCE: The main route of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission is airborne. However, there are few experimental systems that can assess the airborne transmission dynamics of SARS-CoV-2 in vivo. Here, we designed, built, and characterized a hamster transmission caging and exposure system that allows for efficient SARS-CoV-2 airborne transmission in Syrian hamsters without contributions from fomite or direct contact transmission. We successfully measured SARS-CoV-2 viral RNA in aerosols and demonstrated that SARS-CoV-2 is transmitted efficiently at either a 1:1 or 1:4 infected index to naïve recipient hamster ratio. This is meaningful as a 1:4 infected index to naïve hamster ratio would allow for simultaneous comparisons of various interventions in naïve animals to determine their susceptibility to infection by aerosol transmission of SARS-CoV-2. Our SARS-CoV-2 exposure system allows for testing viral airborne transmission dynamics and transmission-blocking therapeutic strategies against SARS-CoV-2 in Syrian hamsters.


Subject(s)
COVID-19 , SARS-CoV-2 , Cricetinae , Animals , Mesocricetus , Respiratory Aerosols and Droplets , Disease Models, Animal
4.
Curr Opin Immunol ; 84: 102374, 2023 10.
Article in English | MEDLINE | ID: mdl-37562075

ABSTRACT

Oral vaccines have a distinctive advantage of stimulating immune responses in the mucosa, where numerous pathogens gain entry and cause disease. Although various efforts have been attempted to create recombinant mucosal vaccines that provoke strong immunogenicity, the outcomes in clinical trials have been weak or inconsistent. Therefore, next-generation mucosal vaccines are needed that are more immunogenic. Here, we discuss oral vaccines with an emphasis on a next-generation mucosal vaccine that utilizes a nonreplicating human recombinant adenovirus type-5 (rAd5) vector. Numerous positive clinical results investigating oral rAd5 vaccines are reviewed, with a summary of the immunogenicity and efficacy results for specific vaccine indications of influenza, norovirus, and SARS-CoV-2. The determination of correlates of protection for oral vaccination and the potential impact this novel vaccine formulation may have on disease transmission are also discussed. In summary, successful oral vaccination can be accomplished and would have major public health benefits if approved.


Subject(s)
COVID-19 , Humans , COVID-19/prevention & control , SARS-CoV-2 , Adenoviridae/genetics , Vaccines, Synthetic , Vaccination , Antibodies, Viral
5.
Front Immunol ; 14: 1086035, 2023.
Article in English | MEDLINE | ID: mdl-36911687

ABSTRACT

SARS-CoV-2 variant clades continue to circumvent antibody responses elicited by vaccination or infection. Current parenteral vaccination strategies reduce illness and hospitalization, yet do not significantly protect against infection by the more recent variants. It is thought that mucosal vaccination strategies may better protect against infection by inducing immunity at the sites of infection, blocking viral transmission more effectively, and significantly inhibiting the evolution of new variants of concern (VOCs). In this study, we evaluated the immunogenicity and efficacy of a mucosally-delivered, non-replicating, adenovirus type 5-vectored vaccine that expresses the spike (S) gene of Wuhan (rAd5-S-Wuhan), delta (rAd5-S-delta), or omicron (rAd5-S-omicron) SARS-CoV-2 VOCs. Hamsters were immunized with these vaccines intranasally prior to challenge with omicron or delta variants. Additionally, one group was vaccinated by oral gavage with rAd5-S-Wuhan prior to challenge with the delta variant. Both intranasal and oral administration of rAd5-S-Wuhan generated cross-reactive serum IgG and mucosal IgA to all variant spike and RBD proteins tested. rAd5-S-omicron and rAd5-S-delta additionally elicited cross-reactive antibodies, though rAd5-S-omicron had significantly lower binding antibody levels except against its matched antigens. Two weeks after the final vaccination, hamsters were challenged with a SARS-CoV-2 variant; omicron or delta. Whether matched to the challenge or with rAd5-S-Wuhan, all vaccines protected hamsters from weight loss and lung pathology caused by challenge and significantly reduced viral shedding compared to placebo. Vaccination with rAd5-S-Wuhan provided significant protection, although there was an improved reduction in shedding and disease pathology in groups protected by the matched VOC vaccines. Nevertheless, Wuhan-based vaccination elicited the most cross-reactive antibody responses generally. Overall, heterologous vaccination via mucosal routes may be advantageous for second-generation vaccines.


Subject(s)
COVID-19 , Vaccines , Animals , Cricetinae , Humans , SARS-CoV-2 , Mesocricetus , Vaccination , Immunization
6.
Sci Transl Med ; 14(658): eabn6868, 2022 08 17.
Article in English | MEDLINE | ID: mdl-35511920

ABSTRACT

Transmission-blocking strategies that slow the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and protect against coronavirus disease 2019 (COVID-19) are needed. We have developed an orally delivered adenovirus type 5-vectored SARS-CoV-2 vaccine candidate that expresses the spike protein. Here, we demonstrated that hamsters vaccinated by the oral or intranasal route had robust and cross-reactive antibody responses. We then induced a postvaccination infection by inoculating vaccinated hamsters with SARS-CoV-2. Orally or intranasally vaccinated hamsters had decreased viral RNA and infectious virus in the nose and lungs and experienced less lung pathology compared to mock-vaccinated hamsters after SARS-CoV-2 challenge. Naïve hamsters exposed in a unidirectional air flow chamber to mucosally vaccinated, SARS-CoV-2-infected hamsters also had lower nasal swab viral RNA and exhibited fewer clinical symptoms than control animals, suggesting that the mucosal route reduced viral transmission. The same platform encoding the SARS-CoV-2 spike and nucleocapsid proteins elicited mucosal cross-reactive SARS-CoV-2-specific IgA responses in a phase 1 clinical trial (NCT04563702). Our data demonstrate that mucosal immunization is a viable strategy to decrease SARS-CoV-2 disease and airborne transmission.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adenoviridae , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , Clinical Trials, Phase I as Topic , Cricetinae , Humans , RNA, Viral , SARS-CoV-2 , Severity of Illness Index
7.
Vaccines (Basel) ; 10(4)2022 Apr 12.
Article in English | MEDLINE | ID: mdl-35455342

ABSTRACT

To effectively combat emerging infections and prevent future pandemics, next generation vaccines must be developed quickly, manufactured rapidly, and most critically, administered easily. Next generation vaccines need innovative approaches that prevent infection, severe disease, and reduce community transmission of respiratory pathogens such as influenza and SARS-CoV-2. Here we review an oral vaccine tablet that can be manufactured and released in less than 16 weeks of antigen design and deployed without the need for cold chain. The oral Ad5 modular vaccine platform utilizes a non-replicating adenoviral vector (rAd5) containing a novel molecular TLR3 adjuvant that is delivered by tablet, not by needle. This enterically coated, room temperature-stable vaccine tablet elicits robust antigen-specific IgA in the gastrointestinal and respiratory tracts and upregulates mucosal homing adhesion molecules on circulating B and T cells. Several influenza antigens have been tested using this novel vaccine approach and demonstrated efficacy in both preclinical animal models and in phase I/II clinical trials, including in a human challenge study. This oral rAd5 vaccine platform technology offers a promising new avenue for aiding in rapid pandemic preparedness and equitable worldwide vaccine distribution.

8.
J Infect Dis ; 225(1): 34-41, 2022 01 05.
Article in English | MEDLINE | ID: mdl-34758086

ABSTRACT

BACKGROUND: Vaccines that are shelf stable and easy to administer are crucial to improve vaccine access and reduce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission around the world. METHODS: In this study, we demonstrate that an oral, adenovirus-based vaccine candidate protects against SARS-CoV-2 in a Syrian hamster challenge model. RESULTS: Hamsters administered 2 doses of VXA-CoV2-1 showed a reduction in weight loss and lung pathology and had completely eliminated infectious virus 5 days postchallenge. Oral immunization induced antispike immunoglobulin G, and neutralizing antibodies were induced upon oral immunization with the sera, demonstrating neutralizing activity. CONCLUSIONS: Overall, these data demonstrate the ability of oral vaccine candidate VXA-CoV2-1 to provide protection against SARS-CoV-2 disease.


Subject(s)
Adenovirus Vaccines/administration & dosage , COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Mesocricetus , Adenovirus Vaccines/immunology , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/virology , COVID-19 Vaccines/immunology , Cricetinae , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccination
9.
Cell Host Microbe ; 29(12): 1828-1837.e5, 2021 12 08.
Article in English | MEDLINE | ID: mdl-34784508

ABSTRACT

Developing new influenza vaccines with improved performance and easier administration routes hinges on defining correlates of protection. Vaccine-elicited cellular correlates of protection for influenza in humans have not yet been demonstrated. A phase-2 double-blind randomized placebo and active (inactivated influenza vaccine) controlled study provides evidence that a human-adenovirus-5-based oral influenza vaccine tablet (VXA-A1.1) can protect from H1N1 virus challenge in humans. Mass cytometry characterization of vaccine-elicited cellular immune responses identified shared and vaccine-type-specific responses across B and T cells. For VXA-A1.1, the abundance of hemagglutinin-specific plasmablasts and plasmablasts positive for integrin α4ß7, phosphorylated STAT5, or lacking expression of CD62L at day 8 were significantly correlated with protection from developing viral shedding following virus challenge at day 90 and contributed to an effective machine learning model of protection. These findings reveal the characteristics of vaccine-elicited cellular correlates of protection for an oral influenza vaccine.


Subject(s)
Immunity , Influenza Vaccines/immunology , Influenza, Human/immunology , Vaccination , Double-Blind Method , Humans , Immunity, Cellular , Immunization , Influenza A Virus, H1N1 Subtype , Influenza A virus , Influenza, Human/prevention & control , L-Selectin/metabolism , STAT5 Transcription Factor/metabolism , T-Lymphocytes , Vaccines, Inactivated/immunology , Virus Shedding
10.
J Safety Res ; 77: 61-66, 2021 06.
Article in English | MEDLINE | ID: mdl-34092329

ABSTRACT

INTRODUCTION: The purpose of this study is to explore the relationship between parents' work-related injuries and their children's mental health, and whether children's work centrality - the extent to which a child believes work will play an important part in their life - exacerbates or buffers this relationship. METHOD: We argue that high work centrality can exacerbate the relationship between parental work injuries and children's mental health, with parental work injuries acting as identity-threatening stressors; in contrast, high work centrality may buffer this relationship, with parental work injuries acting as identity-confirming stressors. We test this relationship with a sample of Canadian children (N = 4,884, 46.2% female, M age = 13.67 years). RESULTS: Children whose parents had experienced more frequent lost-time work-related injuries reported worse mental health with high work centrality buffering this negative relationship. CONCLUSIONS: Our study highlights the vicarious effects of work injuries on salient others, specifically parental work injuries on children's mental health, as well as the role of work centrality in shaping children's sense-making and expectations about the consequences of work.


Subject(s)
Child Health/statistics & numerical data , Mental Health/statistics & numerical data , Occupational Injuries/psychology , Adolescent , Canada , Child , Female , Humans , Male , Parent-Child Relations , Parents/psychology
11.
Nat Med ; 27(1): 125-135, 2021 01.
Article in English | MEDLINE | ID: mdl-33432170

ABSTRACT

Most of what we know about adaptive immunity has come from inbred mouse studies, using methods that are often difficult or impossible to confirm in humans. In addition, vaccine responses in mice are often poorly predictive of responses to those same vaccines in humans. Here we use human tonsils, readily available lymphoid organs, to develop a functional organotypic system that recapitulates key germinal center features in vitro, including the production of antigen-specific antibodies, somatic hypermutation and affinity maturation, plasmablast differentiation and class-switch recombination. We use this system to define the essential cellular components necessary to produce an influenza vaccine response. We also show that it can be used to evaluate humoral immune responses to two priming antigens, rabies vaccine and an adenovirus-based severe acute respiratory syndrome coronavirus 2 vaccine, and to assess the effects of different adjuvants. This system should prove useful for studying critical mechanisms underlying adaptive immunity in much greater depth than previously possible and to rapidly test vaccine candidates and adjuvants in an entirely human system.


Subject(s)
Influenza Vaccines/immunology , Palatine Tonsil/immunology , Adjuvants, Immunologic , B-Lymphocytes/cytology , B-Lymphocytes/immunology , COVID-19 Vaccines/immunology , Germinal Center/cytology , Hemagglutinin Glycoproteins, Influenza Virus , Humans , In Vitro Techniques , Lymphoid Tissue/immunology , Measles-Mumps-Rubella Vaccine/immunology , Organoids/cytology , Organoids/immunology , Rabies Vaccines/immunology , T-Lymphocytes/immunology
12.
Lancet Infect Dis ; 20(4): 435-444, 2020 04.
Article in English | MEDLINE | ID: mdl-31978354

ABSTRACT

BACKGROUND: Influenza is an important public health problem and existing vaccines are not completely protective. New vaccines that protect by alternative mechanisms are needed to improve efficacy of influenza vaccines. In 2015, we did a phase 1 trial of an oral influenza vaccine, VXA-A1.1. A favourable safety profile and robust immunogenicity results in that trial supported progression of the vaccine to the current phase 2 trial. The aim of this study was to evaluate efficacy of the vaccine in a human influenza challenge model. METHODS: We did a single-site, placebo-controlled and active-controlled, phase 2 study at WCCT Global, Costa Mesa, CA, USA. Eligible individuals had an initial A/California/H1N1 haemagglutination inhibition titre of less than 20 and were aged 18-49 years and in good health. Individuals were randomly assigned (2:2:1) to receive a single immunisation of either 1011 infectious units of VXA-A1.1 (a monovalent tablet vaccine) orally, a full human dose of quadrivalent inactivated influenza vaccine (IIV) via intramuscular injection, or matched placebo. Randomisation was done by computer-generated assignments with block size of five. An unmasked pharmacist provided the appropriate vaccines and placebos to the administrating nurse. Individuals receiving the treatments, investigators, and staff were all masked to group assignments. 90 days after immunisation, individuals without clinically significant symptoms or signs of influenza, an oral temperature of higher than 37·9°C, a positive result for respiratory viral shedding on a Biofire test, and any investigator-assessed contraindications were challenged intranasally with 0·5 mL wild-type A/CA/like(H1N1)pdm09 influenza virus. The primary outcomes were safety, which was assessed in all immunised participants through 365 days, and influenza-positive illness after viral challenge, which was assessed in individuals that received the viral challenge and the required number of assessments post viral challenge. This trial is registered with ClinicalTrials.gov, number NCT02918006. RESULTS: Between Aug 31, 2016, and Jan 23, 2017, 374 individuals were assessed for eligibility, of whom 179 were randomly assigned to receive either VXA-A1.1 (n=71 [one individual did not provide a diary card, thus the solicited events were assessed in 70 individuals]), IIV (n=72), or placebo (n=36). Between Dec 2, 2016, and April 26, 2017, 143 eligible individuals (58 in the VXA-A1.1 group, 54 in the IIV group, and 31 in the placebo group) were challenged with influenza virus. VXA-A1.1 was well tolerated with no serious or medically significant adverse events. The most prevalent solicited adverse events for each of the treatment groups after immunisation were headache in the VXA-A1.1 (in five [7%] of 70 participants) and placebo (in seven [19%] of 36 participants) groups and tenderness at injection site in the IIV group (in 19 [26%] of 72 participants) Influenza-positive illness after challenge was detected in 17 (29%) of 58 individuals in the VXA-A1.1 group, 19 (35%) of 54 in the IIV group, and 15 (48%) of 31 in the placebo group. INTERPRETATION: Orally administered VXA-A1.1 was well tolerated and generated protective immunity against virus shedding, similar to a licensed intramuscular IIV. These results represent a major step forward in developing a safe and effective oral influenza vaccine. FUNDING: Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, and Biomedical Advanced Research and Development Authority.


Subject(s)
Administration, Oral , Immunogenicity, Vaccine , Influenza A Virus, H1N1 Subtype/immunology , Influenza Vaccines , Safety , Adult , Double-Blind Method , Female , Headache/etiology , Healthy Volunteers , Humans , Influenza Vaccines/immunology , Influenza Vaccines/therapeutic use , Influenza, Human/immunology , Influenza, Human/prevention & control , Male , Middle Aged , Placebos , Vaccination
13.
J Infect Dis ; 221(6): 919-926, 2020 03 02.
Article in English | MEDLINE | ID: mdl-31628848

ABSTRACT

BACKGROUND: Human noroviruses (HuNoV) are the leading cause of gastroenteritis. No vaccine is currently available to prevent norovirus illness or infection. Safe, infectious challenge strains are needed to assess vaccine efficacy in the controlled human infection model (CHIM). METHODS: A stock of HuNoV strain Norwalk virus ([NV] GI.1) was prepared. Healthy, genetically susceptible adults were inoculated with NV Lot 001-09NV and monitored for infection, gastroenteritis symptoms, and immune responses. RESULTS: Lot 001-09NV induced gastroenteritis in 9 (56%) and infection in 11 (69%) of 16 genetically susceptible subjects. All infected subjects developed strong immune responses to GI.1 with a 30-fold (geometric mean titer) increase in blocking titers (BT50) and a 161-fold increase in GI.1-specific immunoglobulin (Ig)G titers when compared with baseline. GI.1-specific cellular responses in peripheral blood were observed 9 days postchallenge with an average of 3253 IgA and 1227 IgG antibody-secreting cells per million peripheral blood mononuclear cells. CONCLUSIONS: GI.1 Lot 001-09NV appears to be similar in virulence to previous passages of NV strain 8fIIa. The safety profile, attack rate, and duration of illness make GI.1 Lot 001-09NV a useful challenge strain for future vaccine studies aimed at establishing immune correlates.


Subject(s)
Caliciviridae Infections/prevention & control , Caliciviridae Infections/virology , Gastroenteritis/prevention & control , Gastroenteritis/virology , Norwalk virus/classification , Viral Vaccines/immunology , Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult
14.
Accid Anal Prev ; 135: 105372, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31790968

ABSTRACT

In this study, we test the widely held belief that young workers (aged 15-24) are less likely than adults (aged 25 and over) to speak up about safety concerns. Counter to this belief, and in line with age-related resource selectivity theory, we hypothesized that older workers would actually be less likely than younger workers to speak up about workplace safety concerns ("safety voice intentions") when their supervisors are unclear about their own commitment to safety. To test this, we created two realistic scenarios in which we manipulated clarity of supervisor commitment to safety: (1) it is clear the supervisor clearly cares about/is open to hearing suggestions about safety (the "clear commitment" condition) and (2) it is unclear whether the supervisor cares about/is open to hearing suggestions about safety (the "unclear commitment" condition). We randomly assigned participants (N = 80; 58 % women; 40 % over the age of 24) to one of the two scenarios and measured their safety voice intentions. In the face of clear supervisor commitment to safety, younger and adult workers did not differ on their safety voice intentions. However, compared to younger workers, adult workers were less likely to speak up about safety in the face of unclear signals about the supervisor's commitment to safety. These findings have implications for our understanding of young and adult worker safety voice, and the importance of how supervisors signal commitment to safety.


Subject(s)
Occupational Injuries/prevention & control , Safety Management , Adolescent , Adult , Female , Humans , Intention , Leadership , Male , Workplace/psychology , Young Adult
15.
Vaccine ; 37(24): 3146-3150, 2019 05 27.
Article in English | MEDLINE | ID: mdl-31047675

ABSTRACT

Over the past decade, chikungunya virus (CHIKV) has emerged as a major cause of mosquito-borne disease with transmission reported in over 100 countries worldwide. Although several strategies have been pursued for the development of a CHIKV vaccine, none has been approved yet. In this study, we describe the development of several vaccine vectors that express the structural proteins of the La Réunion CHIKV strain LR2006-OPY1. Protection from virus-induced pathologic changes was observed in vaccinated C57BL/6 mice, an important model for CHIKV vaccine development because of their ability to recapitulate several signs shown in infected humans. This study uniquely demonstrates the capacity of a mucosally-administered adenovirus vaccine to induce serum antibody responses and confer protective efficacy in a pre-clinical model. Our data provide further evidence in support of the clinical development of this oral Ad-CHIKV vaccine strategy in populations at high risk of contracting the disease.


Subject(s)
Adenoviridae/immunology , Adjuvants, Immunologic/administration & dosage , Chikungunya Fever/prevention & control , Viral Vaccines/immunology , Administration, Intranasal , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Chikungunya virus , Foot/pathology , Genetic Vectors , Mice , Mice, Inbred C57BL , Vaccines, Attenuated/genetics , Vaccines, Attenuated/immunology , Viral Vaccines/genetics , Viremia/prevention & control
16.
Sci Adv ; 4(9): eaat0625, 2018 09.
Article in English | MEDLINE | ID: mdl-30255141

ABSTRACT

Rapid growth in world trade has enabled transnational criminal networks to conceal their contraband among the 1 billion containers shipped worldwide annually. Forensic methods are needed to identify the major cartels moving the contraband into transit. We combine DNA-based sample matching and geographic assignment of tusks to show that the two tusks from the same elephant are often shipped by the same trafficker in separate large consignments of ivory. The paired shipments occur close in time from the same initial place of export and have high overlap in the geographic origins of their tusks. Collectively, these paired shipments form a linked chain that reflects the sizes, interconnectedness, and places of operation of Africa's largest ivory smuggling cartels.

17.
JCI Insight ; 3(13)2018 07 12.
Article in English | MEDLINE | ID: mdl-29997294

ABSTRACT

BACKGROUND: Noroviruses are the leading cause of epidemic acute gastroenteritis and foodborne diarrheal disease in humans. However, there are no approved vaccines for noroviruses. Potential correlates of protection identified through human challenge studies include mucosal IgA, memory B cells, and serum-blocking antibody titers (BT50). METHODS: We conducted a single-site, randomized, double-blind, placebo-controlled clinical trial of an oral norovirus vaccine to determine safety and immunogenicity. This tablet vaccine is comprised of a nonreplicating adenovirus-based vector expressing the VP1 gene from the GI.1 norovirus strain and a double-stranded RNA adjuvant. Sixty-six adult subjects meeting inclusion/exclusion criteria were randomized 2:1 to receive a single vaccine dose or placebo, respectively. Immunogenicity was primarily assessed by serum BT50. Additional outcomes included serum ELISA titers, fecal and saliva antibody titers, memory and antibody-secreting cell (ASC) frequency, and B cell phenotyping. RESULTS: The vaccine was well-tolerated, with no dose-limiting toxicities. Adverse events were mild or moderate. The primary immunological endpoint (increase in BT50 titers) was met in the high-dose group (P = 0.0003), with 78% showing a ≥2-fold rise in titers after a single immunization. Vaccine recipients also developed mucosally primed VP1-specific circulating ASCs, IgA+ memory B cells expressing gut-homing receptor (α4ß7), and fecal IgA, indicating substantial and local responses potentially relevant to prevent norovirus infection. CONCLUSION: This oral norovirus vaccine was well-tolerated and generated substantial immune responses, including systemic and mucosal antibodies as well as memory IgA/IgG. These results are a major step forward for the development of a safe and immunogenic oral norovirus vaccine. TRIAL REGISTRATION: ClinicalTrials.gov NCT02868073. FUNDING: Vaxart.


Subject(s)
Administration, Oral , Caliciviridae Infections/prevention & control , Norovirus , Tablets/administration & dosage , Tablets/pharmacology , Viral Vaccines/administration & dosage , Viral Vaccines/adverse effects , Viral Vaccines/immunology , Adaptive Immunity , Antibodies, Viral/blood , Antibodies, Viral/immunology , B-Lymphocytes , Caliciviridae Infections/virology , Double-Blind Method , Foodborne Diseases/prevention & control , Foodborne Diseases/virology , Gastroenteritis/prevention & control , Humans , Immunoglobulin A , Norovirus/genetics , United States , Viral Structural Proteins/genetics
18.
Vaccine ; 36(29): 4265-4277, 2018 07 05.
Article in English | MEDLINE | ID: mdl-29895499

ABSTRACT

A vaccine against Respiratory Syncytial Virus (RSV) is a major unmet need to prevent the significant morbidity and mortality that it causes in society. In addition to efficacy, such a vaccine must not induce adverse events, as previously occurred with a formalin-inactivated vaccine (FI-RSV). In this study, the safety, immunogenicity and efficacy of a molecularly adjuvanted adenovirus serotype 5 based RSV vaccine encoding the fusion (F) protein (Ad-RSVF) is demonstrated in cotton rats. Protective immunity to RSV was induced by Ad-RSVF when administered by an oral route as well as by intranasal and intramuscular routes. Compared to FI-RSV, the Ad-RSVF vaccine induced significantly greater neutralizing antibody responses and protection against RSV infection. Significantly, oral or intranasal immunization each induced protective multi-functional effector and memory B cell responses in the respiratory tract. This study uniquely demonstrates the capacity of an orally administered adenovirus vaccine to induce protective immunity in the respiratory tract against RSV in a pre-clinical model and supports further clinical development of this oral Ad-RSVF vaccine strategy.


Subject(s)
Adenoviridae/genetics , Drug Carriers , Respiratory Syncytial Virus Infections/prevention & control , Respiratory Syncytial Virus Vaccines/immunology , Respiratory Syncytial Viruses/immunology , Viral Fusion Proteins/immunology , Administration, Intranasal , Administration, Oral , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , B-Lymphocytes/immunology , Disease Models, Animal , Female , Injections, Intramuscular , Respiratory Syncytial Virus Vaccines/administration & dosage , Respiratory Syncytial Virus Vaccines/genetics , Respiratory Syncytial Viruses/genetics , Sigmodontinae , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/genetics , Vaccines, Synthetic/immunology , Viral Fusion Proteins/genetics
19.
Arthritis Care Res (Hoboken) ; 70(10): 1461-1468, 2018 10.
Article in English | MEDLINE | ID: mdl-29381838

ABSTRACT

OBJECTIVE: To examine the need for and availability and use of formal and informal workplace resources and to uncover differences across the life course in adults with arthritis. METHODS: Focus groups and interviews were conducted with young (aged 18-34 years; n = 7), middle-aged (35-54 years; n = 13), and older adults (≥55 years; n = 25) with a diagnosis of inflammatory arthritis, osteoarthritis, or other rheumatic disease. Participants were asked about their employment experiences, formal and informal workplace resource needs, and availability and use of workplace resources. Differences based on chronological, functional, psychosocial, organizational, and lifespan dimensions of age were examined. A modified grounded theory approach was used to inductively analyze the data. RESULTS: Young, middle-aged, and older adult participants required similar workplace resources. Across all participants, scheduling modifications tended to be the most needed workplace resource. In contrast, the perceived availability and use of formal workplace resources differed among participants. Young adult participants and those who were newer to their jobs reported that workplace resources were less available and utilized. Middle-aged and older adults reported greater availability of workplace resources. Scheduling accommodations and at-work modifications were the workplace resources that were used most by middle-aged and older adults, respectively. CONCLUSION: Similar workplace resources could meet the employment needs of individuals with arthritis across the life course. Attention should be paid to young adults and those who are new to their jobs, because they may perceive more barriers to accessing formal workplace resources and be susceptible to work disability.


Subject(s)
Arthritis , Workplace , Adult , Aged , Female , Humans , Male , Middle Aged , Qualitative Research
20.
Disabil Rehabil ; 40(26): 3127-3135, 2018 12.
Article in English | MEDLINE | ID: mdl-28922952

ABSTRACT

PURPOSE: To understand the similarities and differences in the employment participation of people living with arthritis across the life course. METHOD: Focus groups and interviews were conducted with young (ages 18-34 years, n = 7), middle-aged (ages 35-54 years, n = 13) and older adults (>55 years, n = 25) with arthritis. Participants were asked about the impact of arthritis on employment, experiences with health-related changes, career progression and social role involvement. A modified grounded theory approach was used to inductively analyze the data. RESULTS: Young adults indicated the school-to-work transition as being influential in their employment and described the need to direct their time and energy toward finding work that accommodated health and met career aspirations. Middle-aged adults described how the transition from good health to an arthritis diagnosis disrupted involvement in diverse social roles. However, they often downplayed the impact of arthritis on employment. Older adults described the work-to-retirement transition and their decline in physical functioning as contributing to changing involvement in the labor market. CONCLUSION: Transitions related to health, career progression and social role involvement shaped employment experiences, and represent opportunities for future research and practice that is tailored to life course issues. Implications for rehabilitation Little is known about the work experiences of young- and middle-aged adults with arthritis and how they compare to their older counterparts. Life course theory offers an important framework for research and practice by providing a perspective to enhance our understanding of how employment participation differs across phases of life. Salient and diverse changes related to health, career and social role involvement were identified at each life phase and shaped employment. Rehabilitation practitioners should pay special attention to a client's age, life phase and work history as a strategy to enhance the delivery of interventions that promote work participation.


Subject(s)
Arthritis , Employment , Adult , Age Factors , Arthritis/epidemiology , Arthritis/physiopathology , Arthritis/psychology , Employment/methods , Employment/psychology , Employment/statistics & numerical data , Female , Focus Groups , Grounded Theory , Humans , Interpersonal Relations , Male , Middle Aged , Occupations , Patient Participation , Retirement/psychology , Retirement/statistics & numerical data , Social Identification
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