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Long-term trial of protection provided by adenovirus-vectored vaccine expressing the PPRV H protein.NPJ Vaccines Jun 2024A recombinant, replication-defective, adenovirus-vectored vaccine expressing the H surface glycoprotein of peste des petits ruminants virus (PPRV) has previously been...
A recombinant, replication-defective, adenovirus-vectored vaccine expressing the H surface glycoprotein of peste des petits ruminants virus (PPRV) has previously been shown to protect goats from challenge with wild-type PPRV at up to 4 months post vaccination. Here, we present the results of a longer-term trial of the protection provided by such a vaccine, challenging animals at 6, 9, 12 and 15 months post vaccination. Vaccinated animals developed high levels of anti-PPRV H protein antibodies, which were virus-neutralising, and the level of these antibodies was maintained for the duration of the trial. The vaccinated animals were largely protected against overt clinical disease from the challenge virus. Although viral genome was intermittently detected in blood samples, nasal and/or ocular swabs of vaccinated goats post challenge, viral RNA levels were significantly lower compared to unvaccinated control animals and vaccinated goats did not appear to excrete live virus. This protection, like the antibody response, was maintained at the same level for at least 15 months after vaccination. In addition, we showed that animals that have been vaccinated with the adenovirus-based vaccine can be revaccinated with the same vaccine after 12 months and showed an increased anti-PPRV antibody response after this boost vaccination. Such vaccines, which provide a DIVA capability, would therefore be suitable for use when the current live attenuated PPRV vaccines are withdrawn at the end of the ongoing global PPR eradication campaign.
PubMed: 38830899
DOI: 10.1038/s41541-024-00892-2 -
Journal of Immunological Methods Jul 2024There is a critical need to understand the effectiveness of serum elicited by different SARS-CoV-2 vaccines against SARS-CoV-2 variants. We describe the generation of...
There is a critical need to understand the effectiveness of serum elicited by different SARS-CoV-2 vaccines against SARS-CoV-2 variants. We describe the generation of reference reagents comprised of post-vaccination sera from recipients of different primary vaccines with or without different vaccine booster regimens in order to allow standardized characterization of SARS-CoV-2 neutralization in vitro. We prepared and pooled serum obtained from donors who received a either primary vaccine series alone, or a vaccination strategy that included primary and boosted immunization using available SARS-CoV-2 mRNA vaccines (BNT162b2, Pfizer and mRNA-1273, Moderna), replication-incompetent adenovirus type 26 vaccine (Ad26.COV2·S, Johnson and Johnson), or recombinant baculovirus-expressed spike protein in a nanoparticle vaccine plus Matrix-M adjuvant (NVX-CoV2373, Novavax). No subjects had a history of clinical SARS-CoV-2 infection, and sera were screened with confirmation that there were no nucleocapsid antibodies detected to suggest natural infection. Twice frozen sera were aliquoted, and serum antibodies were characterized for SARS-CoV-2 spike protein binding (estimated WHO antibody binding units/ml), spike protein competition for ACE-2 binding, and SARS-CoV-2 spike protein pseudotyped lentivirus transduction. These reagents are available for distribution to the research community (BEI Resources), and should allow the direct comparison of antibody neutralization results between different laboratories. Further, these sera are an important tool to evaluate the functional neutralization activity of vaccine-induced antibodies against emerging SARS-CoV-2 variants of concern. IMPORTANCE: The explosion of COVID-19 demonstrated how novel coronaviruses can rapidly spread and evolve following introduction into human hosts. The extent of vaccine- and infection-induced protection against infection and disease severity is reduced over time due to the fall in concentration, and due to emerging variants that have altered antibody binding regions on the viral envelope spike protein. Here, we pooled sera obtained from individuals who were immunized with different SARS-CoV-2 vaccines and who did not have clinical or serologic evidence of prior infection. The sera pools were characterized for direct spike protein binding, blockade of virus-receptor binding, and neutralization of spike protein pseudotyped lentiviruses. These sera pools were aliquoted and are available to allow inter-laboratory comparison of results and to provide a tool to determine the effectiveness of prior vaccines in recognizing and neutralizing emerging variants of concern.
Topics: Humans; SARS-CoV-2; Antibodies, Viral; COVID-19; Antibodies, Neutralizing; COVID-19 Vaccines; 2019-nCoV Vaccine mRNA-1273; BNT162 Vaccine; Neutralization Tests; Spike Glycoprotein, Coronavirus; Reference Standards; Immunization, Secondary; Vaccination; Ad26COVS1
PubMed: 38823574
DOI: 10.1016/j.jim.2024.113698 -
NEJM Catalyst Innovations in Care... Feb 2024Health systems could play an important role in efforts to build vaccine confidence in communities that have been hardest hit by Covid-19. Boston Medical Center (BMC)...
Health systems could play an important role in efforts to build vaccine confidence in communities that have been hardest hit by Covid-19. Boston Medical Center (BMC) health system, New England's largest safety-net hospital, along with its community partners, implemented a Covid Response Program aimed at building vaccine confidence. The program was supported by a multifaceted and multilingual communications campaign including: 1) traditional and social media channels with trusted messengers, 2) consistent and accessible core messaging, 3) transparent dialogue, and 4) partnership with state and local health government officials. Between December 2020 and June 2022, BMC disseminated 650 social media posts leading to 12 million impressions and more than 1.8 million post engagements. The campaign included a TikTok video later featured during the presidential inauguration, resulting in more than 3.7 million views. BMC's HealthCity digital publication released 20 articles gaining more than 73,000 views while the FAQ/vaccine scheduling site, translated into seven languages, reached 844,000 page visits. At six months into the vaccination program, 70% of BMC primary care patients 18 years or older had received at least one shot and 60% were fully vaccinated, having received either two mRNA doses or one adenovirus vaccine. The proportions rose to 82% with one dose and 75% fully vaccinated at 12 months. By 24 months into the program, 83% of BMC primary care patients had received at least one shot and 77% were fully vaccinated; however, notable differences existed by race/ethnicity. Seventy six percent of Black patients and 75% of Latino patients were fully vaccinated, compared with 85% of Asian and 81% White patients. Key lessons learned include the importance of a multilingual, multimedia campaign and the need for bidirectional communication that could quickly shift to address evolving issues.
PubMed: 38813133
DOI: 10.1056/cat.23.0322 -
Biomedicine & Pharmacotherapy =... Jul 2024Cancer is one of the major leading causes of mortality globally and chemo-drug-resistant cancers pose significant challenges to cancer treatment by reducing patient...
Cancer is one of the major leading causes of mortality globally and chemo-drug-resistant cancers pose significant challenges to cancer treatment by reducing patient survival rates and increasing treatment costs. Although the mechanisms of chemoresistance vary among different types of cancer, cancer cells are known to share several hallmarks, such as their resistance to apoptosis as well as the ability of cancer stem cells to produce metastatic daughter cells that are resistant to chemotherapy. To address the issue of chemo-drug resistance in cancer cells, a tetracistronic expression construct, Ad-MBR-GFP, encoding adenovirus-mediated expression of MOAP-1, Bax, RASSSF1A, and GFP, was generated to investigate its potential activity in reducing or inhibiting the chemo-drug resistant activity of the human breast cancer cells, MCF-7-CR and MDA-MB-231. When infected by Ad-MBR-GFP, the cancer cells exhibited round cell morphology and nuclei condensation with positive staining for annexin-V. Furthermore, our results showed that both MCF-7-CR and MDA-MB-231 cells stained positively for CD 44 and negatively for CD 24 (CD44+/CD24-) with high levels of endogenous ALDH activity whereas SNU-1581 breast cancer cells were identified as CD 44-/CD 24- cells with relatively low levels of endogenous ALDH activity and high sensitivity toward chemo-drugs, suggesting that both CD 44 and ALDH activity contribute to chemo-drug resistance. Moreover, both MCF-7-CR and MDA-MB-231 cells showed strong chemo-drug sensitivity to cisplatin when the cells were infected by Ad-MBR-GFP, leading to 9-fold and 2-fold reduction in the IC 50 values when compared to cisplatin treatment alone, respectively. The data were further supported by 3D (soft agar) and spheroid cell models of MCF-7-CR and MDA-MB-231 cells which showed a 2-fold reduction of a number of cell colonies and spheroid size when treated with both Ad-MBR-GFP and cisplatin, and compared to control. Other than chemo-sensitivity, Ad-MBR-GFP-infected cancer cells retarded cell migration. Flow cytometry analysis showed that the mechanism of action of Ad-MBR-GFP involved cell cycle arrest at the G1 phase and inhibition of cellular DNA synthesis. Taken together, our investigation showed that Ad-MBR-GFP mediated chemo-drug sensitization in the infected cancer cells involved the activation of apoptosis signaling, cell cycle arrest, and inhibition of DNA synthesis, suggesting that Ad-MBR-GFP is potentially efficacious for the treatment of chemo-drug resistant cancers.
Topics: Humans; Neoplastic Stem Cells; Drug Resistance, Neoplasm; Breast Neoplasms; Adenoviridae; Tumor Suppressor Proteins; Female; bcl-2-Associated X Protein; MCF-7 Cells; Cell Line, Tumor; Biomarkers, Tumor; Apoptosis; Antineoplastic Agents; Cisplatin
PubMed: 38810399
DOI: 10.1016/j.biopha.2024.116744 -
Sisli Etfal Hastanesi Tip Bulteni 2024This study aims to determine the risk factors by examining the sociodemographic characteristics of infants hospitalized in the neonatal intensive care unit (NICU) due to...
OBJECTIVES
This study aims to determine the risk factors by examining the sociodemographic characteristics of infants hospitalized in the neonatal intensive care unit (NICU) due to lower respiratory tract infection (LRTI), to determine the factors that affect the duration of hospitalization, and to determine the underlying microbial factors and evaluate them in the light of the literature.
METHODS
This study evaluated the data of newborns hospitalized with LTRI between 01 October 2022 and 31 March 2023. Demographic characteristics of the patients detected viral agents, duration of hospitalization and risk factors were recorded in the study form. Babies divided viral LRTI and non-viral LRTI, and then compared with each other. Additionally, the facts that might affect the duration of hospitalization were investigated.
RESULTS
The study included 57 babies. Viral agent was detected in 50.9% of the babies, the most frequently viral agent was respiratory syncytial virus (RSV) (48.2%). Other viral factors, in order of frequency; Adenovirus, SARS-CoV-2, Influenza A and B. There is no demographic difference between the viral agent positive and negative groups. The patients were evaluated according to length of hospitalization, it was seen that the hospital stay was longer in babies who were found to be viral positive and needed oxygen therapy (p=0.02, p=0.03, respectively). The male gender ratio was higher in the group with longer hospital stays, but this difference was not statistically significant. Although the rate of exclusive breastfeeding was higher in the group with a short hospitalization period, this difference was not statistically significant (p>0.05).
CONCLUSION
RSV is currently the most frequently detected viral agent in lower respiratory tract infections in newborns. The hospital stay of babies diagnosed with RSV is longer than those with non-RSV viral agents. So struggling with RSV is important in preventing lower respiratory tract infections in newborns. It is necessary to develop a vaccine or immunoglobulin application against RSV infection not only for preterm babies but also for all newborn babies.
PubMed: 38808041
DOI: 10.14744/SEMB.2023.77674 -
Morbidity and Mortality Weekly Report.... May 2024Dengue is the most prevalent mosquitoborne viral illness worldwide and is endemic in Puerto Rico. Dengue's clinical spectrum can range from mild, undifferentiated...
PROBLEM/CONDITION
Dengue is the most prevalent mosquitoborne viral illness worldwide and is endemic in Puerto Rico. Dengue's clinical spectrum can range from mild, undifferentiated febrile illness to hemorrhagic manifestations, shock, multiorgan failure, and death in severe cases. The disease presentation is nonspecific; therefore, various other illnesses (e.g., arboviral and respiratory pathogens) can cause similar clinical symptoms. Enhanced surveillance is necessary to determine disease prevalence, to characterize the epidemiology of severe disease, and to evaluate diagnostic and treatment practices to improve patient outcomes. The Sentinel Enhanced Dengue Surveillance System (SEDSS) was established to monitor trends of dengue and dengue-like acute febrile illnesses (AFIs), characterize the clinical course of disease, and serve as an early warning system for viral infections with epidemic potential.
REPORTING PERIOD
May 2012-December 2022.
DESCRIPTION OF SYSTEM
SEDSS conducts enhanced surveillance for dengue and other relevant AFIs in Puerto Rico. This report includes aggregated data collected from May 2012 through December 2022. SEDSS was launched in May 2012 with patients with AFIs from five health care facilities enrolled. The facilities included two emergency departments in tertiary acute care hospitals in the San Juan-Caguas-Guaynabo metropolitan area and Ponce, two secondary acute care hospitals in Carolina and Guayama, and one outpatient acute care clinic in Ponce. Patients arriving at any SEDSS site were eligible for enrollment if they reported having fever within the past 7 days. During the Zika epidemic (June 2016-June 2018), patients were eligible for enrollment if they had either rash and conjunctivitis, rash and arthralgia, or fever. Eligibility was expanded in April 2020 to include reported cough or shortness of breath within the past 14 days. Blood, urine, nasopharyngeal, and oropharyngeal specimens were collected at enrollment from all participants who consented. Diagnostic testing for dengue virus (DENV) serotypes 1-4, chikungunya virus, Zika virus, influenza A and B viruses, SARS-CoV-2, and five other respiratory viruses was performed by the CDC laboratory in San Juan.
RESULTS
During May 2012-December 2022, a total of 43,608 participants with diagnosed AFI were enrolled in SEDSS; a majority of participants (45.0%) were from Ponce. During the surveillance period, there were 1,432 confirmed or probable cases of dengue, 2,293 confirmed or probable cases of chikungunya, and 1,918 confirmed or probable cases of Zika. The epidemic curves of the three arboviruses indicate dengue is endemic; outbreaks of chikungunya and Zika were sporadic, with case counts peaking in late 2014 and 2016, respectively. The majority of commonly identified respiratory pathogens were influenza A virus (3,756), SARS-CoV-2 (1,586), human adenovirus (1,550), respiratory syncytial virus (1,489), influenza B virus (1,430), and human parainfluenza virus type 1 or 3 (1,401). A total of 5,502 participants had confirmed or probable arbovirus infection, 11,922 had confirmed respiratory virus infection, and 26,503 had AFI without any of the arboviruses or respiratory viruses examined.
INTERPRETATION
Dengue is endemic in Puerto Rico; however, incidence rates varied widely during the reporting period, with the last notable outbreak occurring during 2012-2013. DENV-1 was the predominant virus during the surveillance period; sporadic cases of DENV-4 also were reported. Puerto Rico experienced large outbreaks of chikungunya that peaked in 2014 and of Zika that peaked in 2016; few cases of both viruses have been reported since. Influenza A and respiratory syncytial virus seasonality patterns are distinct, with respiratory syncytial virus incidence typically reaching its annual peak a few weeks before influenza A. The emergence of SARS-CoV-2 led to a reduction in the circulation of other acute respiratory viruses.
PUBLIC HEALTH ACTION
SEDSS is the only site-based enhanced surveillance system designed to gather information on AFI cases in Puerto Rico. This report illustrates that SEDSS can be adapted to detect dengue, Zika, chikungunya, COVID-19, and influenza outbreaks, along with other seasonal acute respiratory viruses, underscoring the importance of recognizing signs and symptoms of relevant diseases and understanding transmission dynamics among these viruses. This report also describes fluctuations in disease incidence, highlighting the value of active surveillance, testing for a panel of acute respiratory viruses, and the importance of flexible and responsive surveillance systems in addressing evolving public health challenges. Various vector control strategies and vaccines are being considered or implemented in Puerto Rico, and data from ongoing trials and SEDSS might be integrated to better understand epidemiologic factors underlying transmission and risk mitigation approaches. Data from SEDSS might guide sampling strategies and implementation of future trials to prevent arbovirus transmission, particularly during the expansion of SEDSS throughout the island to improve geographic representation.
Topics: Puerto Rico; Humans; Dengue; Sentinel Surveillance; Adult; Female; Adolescent; Middle Aged; Child; Male; Child, Preschool; Young Adult; Aged; Infant
PubMed: 38805389
DOI: 10.15585/mmwr.ss7303a1 -
Journal of Family & Community Medicine 2024The aim of this study was to determine the distribution of rotavirus and adenovirus in pediatric patients evaluated for viral gastroenteritis in a hospital in the...
Rotavirus and adenovirus in children evaluated for viral gastroenteritis at a single healthcare center in the Eastern Province of Saudi Arabia: A perspective of two decades.
BACKGROUND
The aim of this study was to determine the distribution of rotavirus and adenovirus in pediatric patients evaluated for viral gastroenteritis in a hospital in the Eastern Province of Saudi Arabia for 22 years.
MATERIALS AND METHODS
This was a retrospective study based in a secondary healthcare center in Saudi Arabia. Laboratory and demographic data were collected from hospital records for all pediatric patients (up to 14 years old) evaluated for viral gastroenteritis by rotavirus/adenovirus antigen detection kit from January 2000 to December 2022. Data were analyzed utilizing SPSS version 28.0. Categorical data were presented as frequency and percentages, whereas mean and standard deviations were computed for continuous variables. Chi-square test and t-test were used to determine statistical significance.
RESULTS
The overall yields of antigen detection were 13.6% for rotavirus and 2.6% for adenovirus. Coinfection with both viruses was documented in 0.5% of the study population. Rotavirus was persistently detected in the past two decades with varying frequency, but the detection of adenovirus showed intervals of at least three consecutive years of zero confirmed cases. Before 2013, when the rotavirus vaccine was introduced in Saudi Arabia, rotavirus was much more prevalent than adenovirus (30% compared to 3.8% in 2010), but they became equally prevalent a decade after the introduction of the vaccine. Rotavirus gastroenteritis showed three different peaks in the year, in March, July, and December. Each peak was followed by a gradual decrease in prevalence before the next peak. Adenovirus, in contrast, was detected consistently around the year at rates between 2% and 5%.
CONCLUSION
Rotavirus and adenovirus gastroenteritis have changed in prevalence in the past two decades. We found distinct seasonal patterns associated with rotavirus and adenovirus gastroenteritis. The utilization of virological testing for pediatric gastroenteritis with syndromic testing panels is to be encouraged to improve the knowledge of the true prevalence of enteric viruses.
PubMed: 38800789
DOI: 10.4103/jfcm.jfcm_273_23 -
Veterinary World Apr 2024Live-attenuated vaccines are the most successful type of vaccine and could be useful in controlling fowl adenovirus (FAdV) 8b infection. This study aimed to attenuate,...
BACKGROUND AND AIM
Live-attenuated vaccines are the most successful type of vaccine and could be useful in controlling fowl adenovirus (FAdV) 8b infection. This study aimed to attenuate, molecularly characterize, and determine the immunogenicity, efficacy, and challenge virus shedding in broiler chickens.
MATERIALS AND METHODS
The FAdV 8b isolate (UPM08136) was passaged onto chicken embryo liver (CEL) cells until attenuation. We sequenced and analyzed the hexon and fiber genes of the passage isolates. The attenuated bioreactor-passage isolate was inoculated into 1-day-old broiler chickens with (attenuated and inactivated) and without booster groups and challenged. Body weight (BW), liver weight (LW), liver: body weight ratio (LBR), FAdV antibody titers, T-lymphocyte subpopulation in the liver, spleen, and thymus, and challenge virus load and shedding were measured.
RESULTS
Typical cytopathic effects with novel genetic changes on CEL cells were observed. The uninoculated control-challenged (UCC) group had significantly lower BW and higher LW and LBR than the inoculated groups. A significantly higher FAdV antibody titer was observed in the challenged non-booster and attenuated booster groups than in the UCC group. T cells in the spleen and thymus of the liver of inoculated chickens were higher than uninoculated control group levels at all-time points and at different times. A significantly higher FAdV challenge virus load was observed in the liver and shedding in the cloaca of UCC chickens than in non-booster chickens.
CONCLUSION
The FAdV 8b isolate was successfully attenuated, safe, and immunogenic. It reduces virus shedding and is effective and recommended as a vaccine against FAdV infection in broiler chickens.
PubMed: 38798289
DOI: 10.14202/vetworld.2024.744-755 -
Vaccines May 2024Ad26.COV2.S vaccination can lead to vaccine-induced immune thrombotic thrombocytopenia (VITT), a rare but severe adverse effect, characterized by thrombocytopenia and...
Ad26.COV2.S vaccination can lead to vaccine-induced immune thrombotic thrombocytopenia (VITT), a rare but severe adverse effect, characterized by thrombocytopenia and thrombosis. The mechanism of VITT induction is unclear and likely multifactorial, potentially including the activation of platelets and endothelial cells mediated by the vaccine-encoded spike protein (S protein). Here, we investigated the biodistribution of the S protein after Ad26.COV2.S dosing in three animal models and in human serum samples. The S protein was transiently present in draining lymph nodes of rabbits after Ad26.COV2.S dosing. The S protein was detected in the serum in all species from 1 day to 21 days after vaccination with Ad26.COV2.S, but it was not detected in platelets, the endothelium lining the blood vessels, or other organs. The S protein S1 and S2 subunits were detected at different ratios and magnitudes after Ad26.COV2.S or COVID-19 mRNA vaccine immunization. However, the S1/S2 ratio did not depend on the Ad26 platform, but on mutation of the furin cleavage site, suggesting that the S1/S2 ratio is not VITT related. Overall, our data suggest that the S-protein biodistribution and kinetics after Ad26.COV2.S dosing are likely not main contributors to the development of VITT, but other S-protein-specific parameters require further investigation.
PubMed: 38793810
DOI: 10.3390/vaccines12050559 -
Vaccines May 2024Adenoviruses are efficient and safe vectors for delivering target antigens and adenovirus-based vaccines have been used against a wide variety of pathogens, including...
Adenoviruses are efficient and safe vectors for delivering target antigens and adenovirus-based vaccines have been used against a wide variety of pathogens, including tuberculosis and COVID-19. Cost-effective and scalable biomanufacturing processes are critical for the commercialization of adenovirus-vectored vaccines. Adenoviral vectors are commonly produced through the infection of batch cultures at low cell density cultures, mostly because infections at high cell densities result in reduced cell-specific virus productivity and does not improve volumetric productivity. In this study, we have investigated the feasibility of improving the volumetric productivity by infecting fed-batch cultures at high cell densities. Four commercial and one in-house developed serum-free media were first tested for supporting growth of HEK 293 cells and production of adenovirus type 5 (Ad5) in batch culture. Two best media were then selected for development of fed-batch culture to improve cell growth and virus productivity. A maximum viable cell density up to 16 × 10 cells/mL was achieved in shake flask fed-batch cultures using the selected media and commercial or in-house developed feeds. The volumetric virus productivity was improved by up to six folds, reaching 3.0 × 10 total viral particles/mL in the fed-batch culture cultivated with the media and feeds developed in house and infected at a cell density of 5 × 10 cells/mL. Additional rounds of optimization of media and feed were required to maintain the improved titer when the fed-batch culture was scaled up in a bench scale (3 L) bioreactor. Overall, the results suggested that fed-batch culture is a simple and feasible process to significantly improve the volumetric productivity of Ad5 through optimization and balance of nutrients in culture media and feeds.
PubMed: 38793775
DOI: 10.3390/vaccines12050524