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Current coronavirus disease-19 (COVID-19) vaccines are administered by the intramuscular route, but this vaccine administration failed to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infection in the upper respiratory tract, mainly due to the absence of virus-specific mucosal immune responses. It is hypothesized that intranasal (IN) vaccination could induce both mucosal and systemic immune responses that blocked SARSCoV-2 transmission and COVID-19 progression. Here, we evaluated in mice IN administration of three modified vaccinia virus Ankara (MVA)-based vaccine candidates expressing the SARS-CoV-2 spike (S) protein, either the full-length native S or a prefusion-stabilized [S(3P)] protein; SARS-CoV-2-specific immune responses and efficacy were determined after a single IN vaccine application. Results showed that in C57BL/6 mice, MVA-based vaccine candidates elicited S-specific IgG and IgA antibodies in serum and bronchoalveolar lavages, respectively, and neutralizing antibodies against parental and SARS-CoV-2 variants of concern (VoC), with MVA-S(3P) being the most immunogenic vaccine candidate. IN vaccine administration also induced polyfunctional Sspecific Th1-skewed CD4+ and cytotoxic CD8+ T-cell immune responses locally (in lungs and bronchoalveolar lymph nodes) or systemically (in spleen). Remarkably, a single IN vaccine dose protected susceptible K18-hACE2 transgenic mice from morbidity and mortality caused by SARS-CoV-2 infection, with MVA-S(3P) being the most effective candidate. Infectious SARSCoV-2 viruses were undetectable in lungs and nasal washes, correlating with high titers of S-specific IgGs and neutralizing antibodies against parental SARSCoV-2 and several VoC. Moreover, low histopathological lung lesions and low levels of pro-inflammatory cytokines in lungs and nasal washes were detected in vaccinated animals. These results demonstrated that a single IN inoculation of our MVA-based vaccine candidates induced potent immune responses, either locally or systemically, and protected animal models from COVID-19. These results also identified an effective vaccine administration route to induce mucosal immunity that should prevent SARS-CoV-2 host-tohost transmission. [ABSTRACT FROM AUTHOR]

The global spread of human monkeypox disease, a zoonotic infection related to smallpox and endemic to West and Central Africa, presents serious challenges for health systems. As of July 2022, 14 533 cases have been reported world-wide, leading to designation as a Public Health Emergency of International Concern. Monkeypox disease is spread from animals to humans through infected lesions or fluids; human-human transmission occurs through fomites, droplets or direct contact. Illness is usually self-limiting, but severe disease can occur in specific groups - particularly children, and people who are immunocompromised or pregnant. Clinical presentation may include fever, lymphadenopathy and skin rash, but the rash may occur without other symptoms. Complications can include secondary bacterial infection of skin lesions, vision loss from corneal involvement, pneumonia, sepsis and encephalitis. Diagnosis of monkeypox requires consideration of epidemiological, clinical and laboratory findings, with sensitive history-taking, to elicit close contacts, critical. Supportive management is usually sufficient, but treatment options (where required) include antivirals and vaccinia immune globulin. A paucity of safety data for relevant antivirals may limit their use. There are two types of monkeypox vaccines: a replication-competent vaccinia vaccine, the use of which is logistically and clinically complex, and a replication-deficient modified vaccinia Ankara virus vaccine. Preparedness of health systems for addressing the current outbreak is constrained by historic underfunding for research, and compounded by stigma and discrimination against cases and affected communities. Key challenges in halting transmission include improving vaccine equity and countering discrimination against men who have sex with men to aid diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Objective: To measure the difference in procedure time between manual vacuum aspiration (MVA) and electric vacuum aspiration (EVA) during abortion procedures between 10 0/7 and 13 6/7 weeks gestation.Study Design: We conducted a 1:1 randomized trial of individuals undergoing an abortion procedure between 10 0/7 and 13 6/7 weeks to MVA or EVA. Procedure time was the primary outcome. We performed an intention-to-treat analysis. A total of 132 patients (66 per arm) were needed to identify a 2-minute difference in time with 90% power and an alpha of 0.05. Given the non-parametric distribution of procedure times, we used Mann-Whitney U test to assess for differences in median procedure times.Results: We randomized 146 participants; 74 to MVA and 72 to EVA. Median procedure times were similar between the 2 groups; EVA 2.4 minutes (range 0.9-6.9 min) and MVA 2.6 minutes (range 1.1-9.0 min, p = 0.12). When stratified by gestational age, EVA between 12 0/7 and 13 6/7 weeks had a shorter median procedure time compared to MVA (2.5 min, range 1.4-6.9 min vs. 3.5 min range 1.7-9.0), respectively (p = 0.005). One conversion occurred from MVA to EVA at 13 weeks.Conclusion: We found no difference in procedure time between MVA and EVA between 10 0/7 and 13 6/7 weeks gestation. MVA does take 1 minute longer than EVA when performed between 12 0/7-13 6/7 weeks; however, this difference is not likely be clinically significant.Implications: Procedure times are similar for manual and electric vacuum aspiration for uterine evacuation between 10 and 14 weeks and the rate of conversion is low. [ABSTRACT FROM AUTHOR]

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen that can transmit from dromedary camels to humans, causing severe pneumonia, with a 35% mortality rate. Vaccine candidates have been developed and tested in mice, camels, and humans. Previously, we developed a vaccine based on the modified vaccinia virus Ankara (MVA) viral vector, encoding a full-length spike protein of MERS-CoV, MVA-MERS. Here, we report the immunogenicity of high-dose MVA-MERS in prime–boost vaccinations in mice and camels. Methods: Three groups of mice were immunised with MVA wild-type (MVA-wt) and MVA-MERS (MVA-wt/MVA-MERS), MVA-MERS/MVA-wt, or MVA-MERS/MVA-MERS. Camels were immunised with two doses of PBS, MVA-wt, or MVA-MERS. Antibody (Ab) responses were evaluated using ELISA and MERS pseudovirus neutralisation assays. Results: Two high doses of MVA-MERS induced strong Ab responses in both mice and camels, including neutralising antibodies. Anti-MVA Ab responses did not affect the immune responses to the vaccine antigen (MERS-CoV spike). Conclusions: MVA-MERS vaccine, administered in a homologous prime–boost regimen, induced high levels of neutralising anti-MERS-CoV antibodies in mice and camels. This could be considered for further development and evaluation as a dromedary vaccine to reduce MERS-CoV transmission to humans. [ABSTRACT FROM AUTHOR]

IntroductionThe Glasgow Coma Scale (GCS) score is the primary method of assessing consciousness after traumatic brain injury (TBI), and the clinical standard for classifying TBI severity. There is scant literature discerning the influence of circadian rhythms or emergency department (ED) arrival hour on this important clinical tool.MethodsRetrospective cohort analysis of adult patients suffering blunt TBI using the National Sample Program of the National Trauma Data Bank, years 2003-2006. ED arrival GCS score was characterized by midday (10 a.m.-4 p.m.) and midnight (12 a.m.-6 a.m.) cohorts (N=24548). Proportions and standard errors are reported for descriptive data. Multivariable regressions using odds ratios (OR), mean differences (B), and their associated 95% confidence intervals [CI] were performed to assess associations between ED arrival hour and GCS score. Statistical significance was assessed at p

Current coronavirus disease-19 (COVID-19) vaccines are administered by the intramuscular route, but this vaccine administration failed to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infection in the upper respiratory tract, mainly due to the absence of virus-specific mucosal immune responses. It is hypothesized that intranasal (IN) vaccination could induce both mucosal and systemic immune responses that blocked SARS-CoV-2 transmission and COVID-19 progression. Here, we evaluated in mice IN administration of three modified vaccinia virus Ankara (MVA)-based vaccine candidates expressing the SARS-CoV-2 spike (S) protein, either the full-length native S or a prefusion-stabilized [S(3P)] protein; SARS-CoV-2-specific immune responses and efficacy were determined after a single IN vaccine application. Results showed that in C57BL/6 mice, MVA-based vaccine candidates elicited S-specific IgG and IgA antibodies in serum and bronchoalveolar lavages, respectively, and neutralizing antibodies against parental and SARS-CoV-2 variants of concern (VoC), with MVA-S(3P) being the most immunogenic vaccine candidate. IN vaccine administration also induced polyfunctional S-specific Th1-skewed CD4+ and cytotoxic CD8+ T-cell immune responses locally (in lungs and bronchoalveolar lymph nodes) or systemically (in spleen). Remarkably, a single IN vaccine dose protected susceptible K18-hACE2 transgenic mice from morbidity and mortality caused by SARS-CoV-2 infection, with MVA-S(3P) being the most effective candidate. Infectious SARS-CoV-2 viruses were undetectable in lungs and nasal washes, correlating with high titers of S-specific IgGs and neutralizing antibodies against parental SARS-CoV-2 and several VoC. Moreover, low histopathological lung lesions and low levels of pro-inflammatory cytokines in lungs and nasal washes were detected in vaccinated animals. These results demonstrated that a single IN inoculation of our MVA-based vaccine candidates induced potent immune responses, either locally or systemically, and protected animal models from COVID-19. These results also identified an effective vaccine administration route to induce mucosal immunity that should prevent SARS-CoV-2 host-to-host transmission.

To stop the HIV-1 pandemic, vaccines must induce responses capable of controlling vast HIV-1 variants circulating in the population as well as those evolved in each individual following transmission. Numerous strategies have been proposed, of which the most promising include focusing responses on the vulnerable sites of HIV-1 displaying the least entropy among global isolates and using algorithms that maximize vaccine match to circulating HIV-1 variants by vaccine cocktails of optimized complementing sequences. In this study, we investigated CD8 T cell responses induced by a bi-valent mosaic of highly conserved HIVconsvX regions delivered by a combination of simian adenovirus ChAdOx1 and poxvirus MVA. We compared partially and fully mono- and bi-valent prime-boost regimens and their ability to elicit T cells recognizing natural epitope variants using an interferon-γ enzyme-linked immunospot (ELISPOT) assay. We used 11 well-defined CD8 T cell epitopes in two mouse haplotypes and, for each epitope, assessed recognition of the two vaccine forms together with the other most frequent epitope variants in the HIV-1 database. We conclude that for the magnitude and depth of epitope recognition, CD8 T cell responses benefitted in most comparisons from the combined bi-valent mosaic and envisage the main advantage of the bi-valent vaccine during its deployment to diverse populations.

Dengue fever, an infectious disease that affects more than 100 million people every year, is a global health problem. Vaccination may be the most effective prevention strategy for the disease. However, the development of vaccines against dengue fever is complicated by the high risk of developing an antibody-dependent increase in infection. This article describes the development of an MVA-d34 vaccine against the dengue virus based on a safe and effective MVA viral vector. The DIII domains of the envelope protein (E) of the dengue virus are used as vaccine antigens, as antibodies against these domains do not cause an enhancement of infection. The use of the DIII domains of each of the four dengue virus serotypes made it possible to generate a humoral response against all four dengue virus serotypes in immunized mice. We also showed that the sera of vaccinated mice present virus-neutralizing activity against dengue serotype 2. Thus, the developed MVA-d34 vaccine is a promising candidate vaccine against dengue fever.

Respiratory syncytial virus (RSV) causes a respiratory disease with a potentially fatal outcome especially in infants and elderly individuals. Several vaccines failed in pivotal clinical trials, and to date, no vaccine against RSV has been licensed. We have developed an RSV vaccine based on the recombinant Modified Vaccinia Virus Ankara-BN® (MVA-RSV), containing five RSV-specific antigens that induced antibody and T-cell responses, which is currently tested in clinical trials. Here, the immunological mechanisms of protection were evaluated to determine viral loads in lungs upon vaccination of mice with MVA-RSV followed by intranasal RSV challenge. Depletion of CD4 or CD8 T cells, serum transfer, and the use of genetically engineered mice lacking the ability to generate either RSV-specific antibodies (T11µMT), the IgA isotype (IgA knockout), or CD8 T cells (β2M knockout) revealed that complete protection from RSV challenge is dependent on CD4 and CD8 T cells as well as antibodies, including IgA. Thus, MVA-RSV vaccination optimally protects against RSV infection by employing multiple arms of the adaptive immune system. [ABSTRACT FROM AUTHOR]

Background: Over-reporting of posttraumatic stress disorder (PTSD) symptoms has been observed in some cases, following a motor vehicle accident (MVA). It has been suggested, however, that these are cases of underdiagnoses in primary care settings. The current study focused on people with PTSD in primary care settings who experienced an MVA and do not seek psychiatric help. Methods: In the over 3000 patient registry of a primary care clinic, 174 people who experienced an MVA (PE-MVA) were identified. The final sample included 45 PE-MVA, who were administered the Clinician-Administered Posttraumatic Stress Disorder Scale (CAPS-2), and completed the Injury Severity Scale (ISS) and the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) content scales. Results: PE-MVA with PTSD reported more psychopathology on both MMPI-2 and CAPS-2 than those without PTSD. Severity of injury, measured by the ISS, did not differ significantly between the two PE-MVA groups. The significant differences between the PE-MVA with PTSD and those without PTSD disappeared after adjusting for the covariates of bias scales [Infrequency (F) and Fake Bad (FBS)] in MMPI-2, but not in CAPS-2. Conclusion: The results suggest that in primary care settings, PE-MVA with PTSD who do not seek psychiatric help, over-report psychiatric and somatic symptoms. In a personal injury setting the F scale of the MMPI-2 showed less sensitivity to exaggerated somatic symptoms than the FBS scale. Bias scales of PE-MVA with PTSD are major contributors to the elevation of the MMPI-2 scores but not the CAPS-2 score. [ABSTRACT FROM AUTHOR]

Mayaro virus (MAYV) is an emerging alphavirus causing acute febrile illness associated with chronic polyarthralgia. Although MAYV is currently restricted to tropical regions in South America around the Amazon basin, it has the potential to spread globally by Aedes species mosquitoes. In addition, there are currently no specific therapeutics or licenced vaccines against MAYV infection. We have previously shown that an adenovirus based Mayaro vaccine (ChAdOx1 May) was able to provide full protection against MAYV challenge in vaccinated A129 mice and induced high neutralising antibody titres. In this study, we have constructed a replication deficient simian adenovirus (ChAdOx2) and a Modified Ankara Virus (MVA) based vaccine expressing the MAYV structural cassette (sMAYV) similar to ChAdOx1 May, and characterised recombinant MAYV E2 glycoprotein expressed in a mammalian system for immune monitoring. We demonstrate that ChAdOx2 May was able to induce high antibody titres similar to ChAdOx1 May, and MVA May was shown to be an effective boosting strategy following prime vaccination with ChAdOx1 or ChAdOx2 May. In order to measure MAYV neutralising ability, we have developed a virus replicon particle-based neutralisation assay which effectively detected neutralising antibodies against MAYV. In summary, our study indicates the potential for further clinical development of the viral vectored MAYV vaccines against MAYV infections. [ABSTRACT FROM AUTHOR]

Vaccination is an effective and economically viable means of protection against the influenza virus, but due to rapid viral evolution, modern seasonal vaccines are not effective enough. Next-generation vaccines are designed to provide protection against a wide range of influenza virus strains, including pandemic variants. In our work, we made an epitope-based universal vaccine, rMVA-k1-k2, against the influenza virus based on the modified vaccinia Ankara (MVA) vector and using our own algorithms to select epitopes from conserved fragments of the NP, M1 and HA proteins of influenza A and B. We show that double immunization protects mice with a 67% or greater efficiency against viral influenza pneumonia when infected with various strains of the H1N1, H2N2, H3N2 and H5N1 subtypes of influenza A. In animals, the level of protection provided by the rMVA-k1-k2 vaccine was comparable to that provided by the universal M001 and MVA-NP+M1 (Invictus) vaccines, which have shown success in clinical trials, against strains of the H1N1 and H3N2 subtypes. [ABSTRACT FROM AUTHOR]

In this research we investigate the impact of stochastic volatility on future initial margin (IM) and margin valuation adjustment (MVA) calculations for interest rate derivatives. An analysis is performed under different market conditions, namely during the peak of the Covid-19 crisis when the markets were stressed and during Q4 of 2020 when volatilities were low. The Cheyette short-rate model is extended by adding a stochastic volatility component, which is calibrated to fit the EUR swaption volatility surfaces. We incorporate the latest risk-free rate benchmarks (RFR), which in certain markets have been selected to replace the IBOR index. We extend modern Fourier pricing techniques to accommodate the RFR benchmark and derive closed-form sensitivity expressions, which are used to model IM profiles in a Monte Carlo simulation framework. The various results are compared to the deterministic volatility case. The results reveal that the inclusion of a stochastic volatility component can have a considerable impact on nonlinear derivatives, especially for far out-of-the-money swaptions. The effect is particularly pronounced if the market exhibits a substantial skew or smile in the implied volatility curve. This can have severe consequences for funding cost valuation and risk management. [ABSTRACT FROM AUTHOR]

Introduction: Spinal cord injury (SCI) is an unbearable neurological disorder. which has a destructive socioeconomic effect of affected individual, their families and the healthcare systems. Stressful spinal cord damages are caused by road traffic misfortunes, violence, sports or falls. Methods: Retrospective study of 112 spinal cord injured patient admitted to Aseer Central hospital (ACH) between the years 2016 and 2018. Results: The present study includes 112 cases of TSCI patients who admitted to Asser Central Hospital and surgically treated, with mean age 32.1 ± 14.12 years. Males were the mostly affected by almost 90.2%. Lower level of education is seen in 69.6% of patients; while only 30.3% of patients had university education or higher. Motor vehicle accidents (MVA) and falls are the only two causes of spinal cord injuries in this study; however, MVA was the cause of SCI in (79.5%) and 20.5% for falls. Conclusions: MVAs are the most source of spinal cord injuries in Southern Saudi Arabia with high male predominance. Despite the lack of significance between shorter time to surgery, and improvement in ASIA score, it was found that shorter time to surgery plays an important role in reducing the post-operative intensive care unit and ward stay, potentially reducing possible long stay related complications and eventually reducing health care cost.

Zika virus (ZIKV) is a mosquito-borne pathogen with public health importance due to the high risk of its mosquito vector dissemination and the severe neurological and teratogenic sequelae associated with infection. Vaccines with broad immune specificity and control against this re-emerging virus are needed. Here, we described that mice immunized with a priming dose of a DNA plasmid mammalian expression vector encoding ZIKV prM-E antigens (DNA-ZIKV) followed by a booster dose of a modified vaccinia virus Ankara (MVA) vector expressing the same prM-E ZIKV antigens (MVA-ZIKV) induced broad, polyfunctional and long-lasting ZIKV-specific CD4+ and CD8+ T-cell immune responses, with high levels of CD4+ T follicular helper cells, together with the induction of neutralizing antibodies. All those immune parameters were significantly stronger in the heterologous DNA-ZIKV/MVA-ZIKV immunization group compared to the homologous prime/boost immunizations regimens. Collectively, these results provided an optimized immunization protocol able to induce high levels of ZIKV-specific T-cell responses, as well as neutralizing antibodies and reinforce the combined use of DNA-based vectors and MVA-ZIKV as promising prophylactic vaccination schedule against ZIKV.

Modified Vaccinia virus Ankara (MVA) is a promising vaccine vector with an outstanding safety profile. The gold standard method to titrate MVA is to immune stain plaques formed in MVA-infected monolayer of primary chicken embryo fibroblasts. Recently, DF-1, an immortal chicken embryo fibroblast line, has also been used. We recently found that MVA plaques in infected DF-1 monolayer could be readily visualized using crystal violet staining, greatly reducing the time and cost of the MVA titration by plaque assay, and with comparable titration results to the gold standard method using immunostaining. Here we present the protocols for MVA amplification and titration using crystal violet- and immuno-staining in DF-1 cells, respectively. Briefly, a fully confluent monolayer of DF-1 cells is infected with MVA at a series of dilutions. The cells are overlaid with media containing methylcellulose, allowing the formation of distinct plaques. After incubating for 2-3 days, the cells are stained with crystal violet or vaccinia virus antiserum, followed by plaque counting., (© 2025. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Respiratory syncytial virus (RSV) causes a respiratory disease with a potentially fatal outcome especially in infants and elderly individuals. Several vaccines failed in pivotal clinical trials, and to date, no vaccine against RSV has been licensed. We have developed an RSV vaccine based on the recombinant Modified Vaccinia Virus Ankara-BN® (MVA-RSV), containing five RSV-specific antigens that induced antibody and T-cell responses, which is currently tested in clinical trials. Here, the immunological mechanisms of protection were evaluated to determine viral loads in lungs upon vaccination of mice with MVA-RSV followed by intranasal RSV challenge. Depletion of CD4 or CD8 T cells, serum transfer, and the use of genetically engineered mice lacking the ability to generate either RSV-specific antibodies (T11µMT), the IgA isotype (IgA knockout), or CD8 T cells (β2M knockout) revealed that complete protection from RSV challenge is dependent on CD4 and CD8 T cells as well as antibodies, including IgA. Thus, MVA-RSV vaccination optimally protects against RSV infection by employing multiple arms of the adaptive immune system.

τ-Cadinol is a sesquiterpene that is widely used in perfume, fine chemicals and medicines industry. In this study, we established a biosynthetic pathway for the first time in engineered Escherichia coli for production of τ-cadinol from simple carbon sources. Subsequently, we further improved the τ-cadinol production to 35.9 ± 4.3 mg/L by optimizing biosynthetic pathway and overproduction of rate-limiting enzyme IdI. Finally, the titer was increased to 133.5 ± 11.2 mg/L with a two-phase organic overlay-culture medium system. This study shows an efficient method for the biosynthesis of τ-cadinol in E. coli with the heterologous hybrid MVA pathway. [ABSTRACT FROM AUTHOR]

Modified vaccinia Ankara (MVA) is a promising vaccine vector due to its highly attenuated phenotype and good immunogenicity. However, obtaining a new recombinant MVA remains a tedious and laborious procedure involving many rounds of plaque purification. Recombinant MVA generation can be greatly improved and facilitated by different selection techniques. Here, we describe a comparison between techniques based on K1L, F13L and D4R genes. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) is a mosquito-borne flavivirus whose infection in pregnant women is associated with a spectrum of birth defects, which are together referred as Congenital Zika Syndrome. In addition, ZIKV can also induce Guillain–Barré syndrome, which is an autoimmune disease with neurological symptoms. The recent description of the first local infections of ZIKV in the European continent together with the expansion of one of its potential vectors, the Asian tiger mosquito (Aedes albopictus), invite us to be prepared for future outbreaks of ZIKV in this geographical region. However, the antigenic similarities of ZIKV with other flaviviruses can lead to an immune cross-reactivity with other circulating flaviviruses inducing, in some cases, flavivirus-disease exacerbation by antibody-dependent enhancement (ADE) of infection, which is a major concern for ZIKV vaccine development. Until now, West Nile virus (WNV) is the main medically relevant flavivirus circulating in the Mediterranean Basin. Therefore, anticipating the potential scenario of emergency vaccination against ZIKV in areas of Europe where WNV is endemic, in this investigation, we have evaluated the cross-reactivity between WNV and our previously developed ZIKV vaccine candidate based on modified vaccinia virus Ankara (MVA) vector expressing ZIKV structural proteins (MVA-ZIKV). To this end, mice were first immunized with MVA-ZIKV, subsequently challenged with WNV, and then, the ZIKV- and WNV-specific immune responses and protection against WNV were evaluated. Our results indicate low cross-reactivity between the MVA-ZIKV vaccine candidate and WNV and absence of ADE, supporting the safety of this ZIKV vaccine candidate in areas where the circulation of WNV is endemic. [ABSTRACT FROM AUTHOR]

Bluetongue, caused by bluetongue virus (BTV), is a widespread arthropod-borne disease of ruminants that entails a recurrent threat to the primary sector of developed and developing countries. In this work, we report modified vaccinia virus Ankara (MVA) and ChAdOx1-vectored vaccines designed to simultaneously express the immunogenic NS1 protein and/or NS2-Nt, the N-terminal half of protein NS2 (NS21-180). A single dose of MVA or ChAdOx1 expressing NS1-NS2-Nt improved the protection conferred by NS1 alone in IFNAR(-/-) mice. Moreover, mice immunized with ChAdOx1/MVA-NS1, ChAdOx1/MVA-NS2-Nt, or ChAdOx1/MVA-NS1-NS2-Nt developed strong cytotoxic CD81 T-cell responses against NS1, NS2-Nt, or both proteins and were fully protected against a lethal infection with BTV serotypes 1, 4, and 8. Furthermore, although a single immunization with ChAdOx1-NS1-NS2-Nt partially protected sheep against BTV-4, the administration of a booster dose of MVA-NS1- NS2-Nt promoted a faster viral clearance, reduction of the period and level of viremia and also protected from the pathology produced by BTV infection. [ABSTRACT FROM AUTHOR]

This research is the concept of proving the function and / or important factors analytically and experimentally. This study aims to analyze investment decisions as measured by stock prices with performance measures as the independent variable. Company performance measures measured through economic value added (EVA), market value added (MVA), Return on Equity (ROE), and Earning Per Share (EPS). The research method used is quantitative research and the sample of this study is an investor index company listed on the Indonesia Stock Exchange (BEI) in 2015 - 2018. The method of analysis used is multiple regression test. The results of this study indicate that EVA and MVA have no effect on stock prices, while ROE and EPS have an effect on stock prices. So it can be denied that investors in Indonesia, company investors 33, look at the figures shown in historical financial reports more than they look at the residual income.

Abstract Background Microbial cell factories are usually engineered and employed for cultivations that combine product synthesis with growth. Such a strategy inevitably invests part of the substrate pool towards the generation of biomass and cellular maintenance. Hence, engineering strains for the formation of a specific product under non-growth conditions would allow to reach higher product yields. In this respect, isoprenoid biosynthesis represents an extensively studied example of growth-coupled synthesis with rather unexplored potential for growth-independent production. Rhodobacter sphaeroides is a model bacterium for isoprenoid biosynthesis, either via the native 2-methyl-d-erythritol 4-phosphate (MEP) pathway or the heterologous mevalonate (MVA) pathway, and for poly-β-hydroxybutyrate (PHB) biosynthesis. Results This study investigates the use of this bacterium for growth-independent production of isoprenoids, with amorpha-4,11-diene as reporter molecule. For this purpose, we employed the recently developed Cas9-based genome editing tool for R. sphaeroides to rapidly construct single and double deletion mutant strains of the MEP and PHB pathways, and we subsequently transformed the strains with the amorphadiene producing plasmid. Furthermore, we employed 13C-metabolic flux ratio analysis to monitor the changes in the isoprenoid metabolic fluxes under different cultivation conditions. We demonstrated that active flux via both isoprenoid pathways while inactivating PHB synthesis maximizes growth-coupled isoprenoid synthesis. On the other hand, the strain that showed the highest growth-independent isoprenoid yield and productivity, combined the plasmid-based heterologous expression of the orthogonal MVA pathway with the inactivation of the native MEP and PHB production pathways. Conclusions Apart from proposing a microbial cell factory for growth-independent isoprenoid synthesis, this work provides novel insights about the interaction of MEP and MVA pathways under different growth conditions.

Artemisia argyi Levl. et Van (A. argyi) is a traditional medicinal plant, which is widely used in health, food and medicine. Thujone is an important cyclic monoterpene derivative in the volatile oil of A. argyi leaves with multiple efficacy. Although the thujone synthetic pathway has been preliminarily analyzed in very few species, genes related to the thujone content in A. argyi leaves remain largely unknown. In this study, we identify candidate genes involved in the synthesis and regulation of thujone content in A. argyi leaves by the comparative transcriptome analysis of two group materials with high and low thujone content. A total of 89 candidate genes related to thujone content are identified including one gene involved in the mevalonate pathway, three genes involved in the methylerythritol phosphate pathway, 19 genes involved in the metabolic process from geranyl pyrophosphate to thujone (four b-terpene synthase, five cytochrome P450, five dehydrogenase, and five reductase-encoding genes) and 66 transcription factor-encoding genes. Taken together, our results provide valuable gene resources for further analyzing the synthetic and regulatory pathway of thujone in A. argyi.

The combination of mosaic Gag and CAP256 envelope in an HIV vaccine regimen comprising DNA prime and modified vaccinia Ankara (MVA) boost followed by protein boost has previously been shown to generate robust autologous Tier 2 neutralizing antibodies (nAbs) in rabbits. Further refinements of this strategy have been investigated to improve antibody responses. The delivery of both DNA and recombinant MVA vaccines with a needle-free device was compared to delivery by injection, and the effect of formulating the DNA vaccine with adjuvant CpG ODN 1826 was determined. The Pharmajet Stratis® needle-free injection device (PharmaJet, Golden, CO, USA) improved binding antibody responses to the DNA vaccine as well as both binding and neutralizing antibody responses to the MVA vaccines. Formulation of the DNA vaccines with CpG adjuvant further improved the antibody responses. A shortened vaccination regimen of a single DNA inoculation followed by a single MVA inoculation did not elicit Tier 1B nor Tier 2 neutralization responses as produced by the two DNA, followed by two MVA vaccination regimen. This study showed the immunogenicity of HIV DNA and MVA vaccines administered in a DDMM regimen could be improved using the PharmaJet Stratis needle-free injection device and formulation of the DNA vaccines with CpG adjuvant.

In response to the mpox outbreak in 2022 and 2023, widespread vaccination with modified vaccinia Ankara-Bavarian Nordic (MVA-BN, also known as JYNNEOS or Imvanex) was initiated. Here, we demonstrate that orthopoxvirus-specific binding and MVA-neutralising antibodies waned to undetectable levels 1 year post vaccination in at-risk individuals who received two doses of MVA-BN administered subcutaneously with an interval of 4 weeks, without prior smallpox or mpox vaccination. Continuous surveillance is essential to understand the impact of declining antibody levels.

Licensed vaccines against the Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging pathogen of concern, are lacking. The modified vaccinia virus Ankara vector-based vaccine MVA-MERS-S, expressing the MERS-CoV-spike glycoprotein (MERS-S), is one of 3 candidate vaccines in clinical development and elicits robust humoral and cellular immunity. Here, we identified for the first time a MERS-S-specific CD8+ T-cell epitope in an HLA-A*03:01/HLA-B*35:01-positive vaccinee using a screening assay, intracellular cytokine staining, and in silico epitope prediction. As evidence from MERS-CoV infection suggests a protective role of long-lasting CD8+ T-cell responses, the identification of epitopes will facilitate longitudinal analyses of vaccine-induced T-cell immunity., Competing Interests: Potential conflicts of interest. T. W. received consulting fees and honoraria from Gilead Sciences and Merck Sharp Dome. All other authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Vaccinia viruses (VACVs) are versatile therapeutic agents and different features of various VACV strains allow for a broad range of therapeutic applications. Modified VACV Ankara (MVA) is a particularly altered VACV strain that is highly immunogenic, incapable of replicating in mammalian hosts, and broadly used as a safe vector for vaccination. Alternatively, Western Reserve (WR) or Copenhagen (Cop) are VACV strains that efficiently replicate in cancer cells and, therefore, are used to develop oncolytic viruses. However, the immune evasion capacity of WR or Cop hinders their ability to elicit antitumor immune responses, which is crucial for efficacy in the clinic. Here, we describe a new VACV strain named Immune-Oncolytic VACV Ankara (IOVA), which combines efficient replication in cancer cells with induction of immunogenic tumor cell death (ICD). IOVA was engineered from an MVA ancestor and shows superior cytotoxicity in tumor cells. In addition, the IOVA genome incorporates mutations that lead to massive fusogenesis of tumor cells, which contributes to improved antitumor effects. In syngeneic mouse tumor models, the induction of ICD results in robust antitumor immunity directed against tumor neo-epitopes and eradication of large established tumors. These data present IOVA as an improved immunotherapeutic oncolytic vector., Competing Interests: Declaration of interests J.J.R. and G.S. have filed the patent application WO2019106205A1 and are named as inventors on this patent application describing the use of immune oncolytic VACV., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Recombinant viral vectors represent an important platform for vaccine delivery. Our recent studies have demonstrated distinct innate immune profiles in responding to viral vectors of different families (e.g., adenovirus versus poxvirus): while human Ad5 vector is minimally innate immune stimulatory, the poxviral vector ALVAC induces strong innate response and stimulates type I interferon (IFN) and inflammasome activation. However, the impact of the innate immune signaling on vaccine-induced adaptive immunity in viral vector vaccination is less clear. Here, we show that Modified Vaccinia Ankara (MVA), another poxviral vector, stimulated a type I IFN response in innate immune cells through cGAS-STING. Using MVA-HIV vaccine as a model, we found that type I IFN signaling promoted the generation of humoral immunity in MVA-HIV vaccination in vivo. Following vaccination, type I IFN receptor-knockout (IFNAR1-/-) mice produced significantly lower levels of total and HIV gp120-specific antibodies compared to wild-type (WT) mice. Consistent with the antibody response, a type I IFN signaling deficiency also led to reduced levels of plasma cells and memory-like B cells compared to WT mice. Furthermore, analysis of vaccine-induced CD4 T cells showed that type I IFN signaling also promoted the generation of a vaccine-specific CD4 T-cell response and a T follicular helper (Tfh) response in mice. Together, our data indicate a role for type I IFN signaling in promoting humoral immunity in poxviral vector vaccination. The study suggests that modulating type I IFN and its associated innate immune pathways will likely affect vaccine efficacy. [ABSTRACT FROM AUTHOR]

• MVAΔ008-OVA induces ex vivo IFN-γ secretion and in vivo cytotoxicity response against OVA. • This response has higher magnitude than the elicited by the conventional MVA vector. • Recombinant MVAs induce full protection against MO5 challenge (prophylactic scheme). • In a therapeutic scheme, both MVAs delay tumor growth and prolong mice survival. Modified vaccinia Ankara virus (MVA) is extensively used as a vaccine vector. We have previously observed that MVAΔ008, an MVA lacking the gene that codes for interleukin-18 binding protein, significantly increases CD8+ and CD4+ T-cell responses to vaccinia virus (VACV) epitopes and recombinant HIV antigens. However, the efficacy of this vector against pathogens or tumor cells remains unclear. Thus, the aim of this study was to evaluate the cellular immune response and the protection induced by recombinant MVAs encoding the model antigen ovalbumin (OVA). We used the MO5 melanoma tumor model (OVA-expressing tumor) as an approach for evaluating the vector-induced efficacy. Our results show that MVAΔ008-OVA (optimized vector) induced higher in vivo specific cytotoxicity and ex vivo T-cell IFN-γ responses against OVA than the conventional MVA vector. Importantly, the recombinant vectors were capable of controlling MO5 tumor growth. Indeed, the administration of MVAΔ008-OVA or MVA-OVA in prophylactic and therapeutic schemes provided total protection and longer survival of mice, respectively. Overall, our results demonstrate the improved immunogenicity and the protective capacity of MVAΔ008 against a heterologous model antigen. These findings suggest that MVAΔ008 constitutes an excellent candidate for vaccine development against pathogens or cancer therapy. [ABSTRACT FROM AUTHOR]

Modified vaccinia virus Ankara (MVA) was derived by repeated passaging in chick fibroblasts, during which deletions and mutations rendered the virus unable to replicate in most mammalian cells. Marker rescue experiments demonstrated that the host range defect could be overcome by replacing DNA that had been deleted from near the left end of the genome. One virus isolate, however, recovered the ability to replicate in monkey BS-C-1 cells but not human cells without added DNA, suggesting that it arose from a spontaneous mutation. Here, we showed that variants with enhanced ability to replicate in BS-C-1 cells could be isolated by blind passaging of MVA and that in each there was a point mutation leading to an amino acid substitution in the D10 decapping enzyme. The sufficiency of these single mutations to enhance host range was confirmed by constructing recombinant viruses. The D10 mutations occurred at N- or C-terminal locations distal to the active site, suggesting an indirect effect on decapping or on another previously unknown role of D10. Although increased amounts of viral mRNA and proteins were found in BS-C-1 cells infected with the mutants compared to those with parental MVA, the increases were much less than the 1- to 2-log-higher virus yields. Nevertheless, a contributing role for diminished decapping in overcoming the host range defect was consistent with increased replication and viral protein synthesis in BS-C-1 cells infected with an MVA engineered to have active-site mutations that abrogate decapping activity entirely. Optimal decapping may vary depending on the biological context. [ABSTRACT FROM AUTHOR]

The aim of the study was to assess the value and applicability of multivariate tools for hematological and plasma biochemical responses of fish living in treated wastewater. Physicochemical water properties and heavy metals concentration of water in spring and fall were used as determinants of multiple fish stressors. Three methods of data analysis (Agglomerative Hierarchical Clustering, Factor Analysis, Principal Component Analysis) and one method of data modeling (Partial Least Square Regression) were applied. These methods enabled identification of clustering based on observed parameters, identification of significant variables in the observed data set, and correlation of observed variables with samples collected in different places and at different seasons. Prediction of total leukocytes, lymphocytes, granulocytes, hematocrit, glucose, alanine aminotransferase, triglycerides and cholesterol from fish blood (R2 > 0.9) was better for fall than for spring variables, regardless the sampling site (R2 > 0.98). For hematocrit and glucose (determination coefficient over 0.99), prediction was successful regardless the season and the sampling site. The effectiveness of prediction models was also evaluated using ratio of standard error of performance to standard deviation (RPD), and range error ratio (RER). High applicability of these models was found for multiple purposes (RPD > 8 and RER > 15), including prediction of parameters from fish blood with regard to water quality.

Mitral valve aneurysm (MVA) is a rare but life-threatening valvular pathologic entity most commonly associated with infective endocarditis (IE) of the aortic valve (AV). We describe a diabetic patient with ruptured anterior MVA secondary to capsular genotype V Streptococcus agalactiae (GBS) harboring novel ST1656 IE without AV involvement. Our patient presented with manifestations of various serious systemic and intracardiac complications, requiring early surgery, but ultimately died from non-cardiogenic causes. This case emphasizes the importance of treating MVA as a dangerous sequela of IE, of performing transesophageal echocardiography to make its accurate diagnosis and institute early surgical intervention, and of considering GBS as a rare but important causative agent of IE in elderly patients with comorbidities.

Purpose: To determine the therapeutic effect of Xuezhitong capsule in patients with microvascular angina (MVA), and its impact on vascular endothelial function. Methods: In total, 172 MVA patients treated in Beijing City Fengtai District Nanyuan Hospital from September 2017 to September 2019 were selected and randomized into control group which received conventional treatment, and treatment group which received Xuezhitong capsules plus. There were 86 patients in each group. Therapeutic effect, levels of inflammatory factors, i.e., high-sensitivity C-reactive protein (hs-CRP), interleukin-(IL-6), tumor necrosis factor-α (TNF-α), and vascular endothelial factors such as nitric oxide (NO), thromboxane B2 (TXB2) and endothelin (ET), were determined. Results: Markedly higher total treatment effectiveness was observed in the treatment group than in the control group (89.53 % vs. 72.94 %; p < 0.05). In both groups, treatment reduced the levels of hs-CRP, IL-6, TNF-α, TXB2 and ET, but elevated NO, with better results for treatment group than the control group (p < 0.05). Better optimizations of total cholesterol (TC), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein (HDL) were observed in the treatment group, relative to the control group (p < 0.05). Patients in the treatment group experienced fewer (8.14 %) adverse reactions than those in control group (21.18 %, p < 0.05). Conclusion: Xuezhitong capsule, when combined with conventional treatment, exerts high therapeutic effectiveness and safety in MVA patients by inhibiting inflammatory reactions, optimizing endothelial function, reducing blood lipid levels, and decreasing the incidence of cardiovascular adverse events. Thus, the combination therapy is a potentially superior therapeutic strategy to the conventional approach for the management of MVA patients. [ABSTRACT FROM AUTHOR]

Penilaian kinerja menjadi sangat penting untuk perusahaan yang telah terbuka karena perusahaan tersebut harus senantiasa mampu melakukan penciptaan nilai. Penilaian kinerja internal dilakukan untuk membantu menentukan strategi yang sesuai dengan keadaan perusahaan. Penilaian kinerja eksternal bertujuan untuk pengambilan keputusan investasi bagi investor. Penelitian ini merupakan penelitian kualitatif dengan menggunakan 30 perusahaan consumer goods dan dilakukan analisis dari tahun 2011 hingga 2015. Hasil dari penelitian ini dari sisi penilaian kinerja internal adalah 8 perusahaan masuk dalam kuadran A financial strategy matrix, 14 perusahaan masuk dalam kuadran B financial strategy matrix, 2 perusahaan masuk dalam kuadran C financial strategy matrix, 6 perusahan masuk dalam kuadran D financial strategy matrix. Hasil dari penilaian kinerja eksternal adalah 8 perusahaan masuk dalam kuadran excellent value managers, 11 perusahaan masuk dalam kuadran expectation builders, 11 perusahaan masuk dalam kuadran traditionalist, tidak ada yang masuk dalam kuadran asset loaded value managers. Kinerja internal dan eksternal yang baik dari sampel 30 perusahaan, hanya 4 perusahaan yang memiliki kinerja baik, yaitu ADES, HMSP, UNVR, dan MLBI. Implikasi penelitian ini adalah kinerja internal dan eksternal melihat pada EPS (Earning Per Share). EPS di kinerja internal digunakan saat menentukan SGR (Sustainable Growth Rate) atau pertumbuhan sesungguhnya yang harus dicapai perusahaan dari financial strategy matrix. EPS di kinerja eksternal digunakan untuk menentukan current performance. Secara keseluruhan, kinerja internal dan eksternal membentuk penciptaan nilai untuk pemegang saham dalam bentuk laba yang siap dibagikan kepada pemegang saham.

Abstract Background Malawi has one of the highest maternal mortality rates in the world, with unsafe abortion as a major contributor. Curettage is most frequently used as the surgical method for treating incomplete abortions, even though it is costly for an impoverished health system and the less expensive and safe manual vacuum aspiration (MVA) method is recommended. Methods The aim of this 2016–17 study is to explore health worker’s perception of doing MVA 1 year after an educational intervention. Focus group discussions were recorded, transcribed verbatim, and analyzed using content analysis for interpreting the findings. A knowledge, attitude and practice survey was administered to health professionals to obtain background information before the MVA training program was introduced. Results Prior to the training sessions, the participants demonstrated knowledge on abortion practices and had positive attitudes about participating in the service, but preferred curettage over MVA. The training was well received, and participants felt more confident in doing MVA after the intervention. However, focus group discussions revealed obstacles to perform MVA such as broken equipment and lack of support. Additionally, the training could have been more comprehensive. Still, the participants appreciated task-sharing and team work. Conclusion Training sessions are considered useful in increasing the use of MVA. This study provides important insight on how to proceed in improving post-abortion care in a country where complications of unsafe abortion are common and the health system is low on resources.

Modified vaccinia virus Ankara (MVA) is a replication-deficient poxvirus, attenuated in chick embryo fibroblast primary cells. It has been utilised as a viral vector to develop many vaccines against cancer and infectious diseases such as malaria, HIV/AIDS, influenza, and tuberculosis, MERS-CoV, and Ebola virus infection. There is accumulating data from many preclinical and clinical studies that highlights the excellent safety and immunogenicity of MVA. However, due to the complex nature of many pathogens and their pathogenicity, MVA vectored vaccine candidates need to be optimised to improve their immunogenicity. One of the main approaches to improve MVA immunogenicity focuses on optimising poxviral promoters that drive recombinant vaccine antigens, encoded within recombinant MVA vector genome. A number of promoters were described or optimised to improve the development of MVA based vaccines such as p7.5, pF11, and mH5 promoters. This review focuses on poxviral promoters, their optimisation, genetic stability, and clinical use.

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen that can transmit from dromedary camels to humans, causing severe pneumonia, with a 35% mortality rate. Vaccine candidates have been developed and tested in mice, camels, and humans. Previously, we developed a vaccine based on the modified vaccinia virus Ankara (MVA) viral vector, encoding a full-length spike protein of MERS-CoV, MVA-MERS. Here, we report the immunogenicity of high-dose MVA-MERS in prime–boost vaccinations in mice and camels. Methods: Three groups of mice were immunised with MVA wild-type (MVA-wt) and MVA-MERS (MVA-wt/MVA-MERS), MVA-MERS/MVA-wt, or MVA-MERS/MVA-MERS. Camels were immunised with two doses of PBS, MVA-wt, or MVA-MERS. Antibody (Ab) responses were evaluated using ELISA and MERS pseudovirus neutralisation assays. Results: Two high doses of MVA-MERS induced strong Ab responses in both mice and camels, including neutralising antibodies. Anti-MVA Ab responses did not affect the immune responses to the vaccine antigen (MERS-CoV spike). Conclusions: MVA-MERS vaccine, administered in a homologous prime–boost regimen, induced high levels of neutralising anti-MERS-CoV antibodies in mice and camels. This could be considered for further development and evaluation as a dromedary vaccine to reduce MERS-CoV transmission to humans.

Novel 2‐domain PSA pixel design was proposed to get better viewing angle experience. Furthermore, the viewing angle is IPS‐like level, and the transmittance gain is about 10.5% compared with the conventional 4‐domain PSA pixel. [ABSTRACT FROM AUTHOR]

A seismic survey identified a basalt flow that could consist of cap rock of CO2 storage beneath saline aquifer sediment in the Southern Continental Shelf of Korea. To determine the precise depth of the basalt flow, specific depth-domain data processing of migration velocity analysis (MVA) was applied to the seismic survey data. The accurate depth measurement of a target structure provides crucial information when storing and stabilizing injected CO2 beneath basalt cap rock. Strong reflections of seismic amplitude at the volcanic mounds were adjusted from the time domain to the exact depth domain by the iterated velocity using MVA. The confidence of the updated velocity was verified by the horizontal alignment of seismic events sorted according to their common reflection point (CRP). The depth difference in volcanic mounds before and after MVA application ranged from 32.5 to 60 m along the vertical axis, showing the eruption shape on the strong-amplitude contour map in detail. The eruption shape of the top of volcanic mounds was verified with spatial continuity in 3D geological interpretation. The presented results provide suitable information that can be used to locate drilling sites and to prepare CO2 injection. The geological model obtained from both time- and depth-domain processing can significantly influence the calculation of the storage volume and can be useful for history matching studies. [ABSTRACT FROM AUTHOR]

Introduction: Spinal cord injury (SCI) is an unbearable neurological disorder. which has a destructive socioeconomic effect of affected individual, their families and the healthcare systems. Stressful spinal cord damages are caused by road traffic misfortunes, violence, sports or falls. Methods: Retrospective study of 112 spinal cord injured patient admitted to Aseer Central hospital (ACH) between the years 2016 and 2018. Results: The present study includes 112 cases of TSCI patients who admitted to Asser Central Hospital and surgically treated, with mean age 32.1 ± 14.12 years. Males were the mostly affected by almost 90.2%. Lower level of education is seen in 69.6% of patients; while only 30.3% of patients had university education or higher. Motor vehicle accidents (MVA) and falls are the only two causes of spinal cord injuries in this study; however, MVA was the cause of SCI in (79.5%) and 20.5% for falls. Conclusions: MVAs are the most source of spinal cord injuries in Southern Saudi Arabia with high male predominance. Despite the lack of significance between shorter time to surgery, and improvement in ASIA score, it was found that shorter time to surgery plays an important role in reducing the post-operative intensive care unit and ward stay, potentially reducing possible long stay related complications and eventually reducing health care cost. [ABSTRACT FROM AUTHOR]

The interactions of polymeric methylene diphenyl di‐isocyanate (pMDI) and a model Fe–Cr alloy have been studied by X‐ray photoelectron spectroscopy (XPS) and time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS). Films of two different thicknesses have been investigated: one with an extremely thin pMDI layer in which the interfacial chemistry can be probed directly and a thicker one in which sputter profiling using cluster ions is necessary to expose the interface chemistry for direct analysis. Multivariate analysis (MVA), using principal component analysis (PCA) and nonnegative matrix factorisation (NMF), has been used to identify specific ions associated with the interfacial region of the ToF‐SIMS sputter depth profile and chemical species from the XPS sputter depth profile. As an unsupervised method, this avoids an unconscious bias on the part of the analyst. Specific ions associated with pMDI interactions with both Fe and Cr allow the proposal of two complementary reaction mechanisms, supported by the XPS data. A range of cluster ions is used in this investigation, but the bulk of the work used argon clusters for the XPS depth profiles and Buckminster Fullerene projectiles for the ToF‐SIMS analyses. To ensure that such data were directly comparable, the ToF‐SIMS sputter profiles were repeated in a different system of the same type using argon cluster ions. [ABSTRACT FROM AUTHOR]

Two HIV-1 vaccines (SAAVI DNA-C2 and SAAVI MVA-C) were previously developed in South Africa and tested in preclinical studies and Phase 1 clinical trials. Here we report on improvements made to the SAAVI MVA-C vaccine design which include: the use of different promoters for both the Gag and Env genes, replacement of the native Gag gene with an in silico designed subtype C mosaic Gag antigen which forms virus-like particles and the modification of Env by sequence changes to improve stability and transport to the cell surface. A head-to-head comparison of the newly conceived MVAGD5 candidate vaccine with SAAVI MVA-C showed increased in vitro expression of both Env and Gag, and superior immunogenicity in rabbits. MVAGD5 induced high levels of binding antibodies to Env and Tier 1A and 1B neutralizing antibodies, neither of which were induced by SAAVI MVA-C. [ABSTRACT FROM AUTHOR]

Bovine respiratory syncytial virus (BRSV) affects both beef and dairy cattle, reaching morbidity and mortality rates of 60-80% and 20%, respectively. The aim of this study was to obtain a recombinant MVA expressing the BRSV F protein (MVA-F) as a vaccine against BRSV and to evaluate the immune response induced by MVA-F after systemic immunization in homologous and heterologous vaccination (MVA-F alone or combined with a subunit vaccine), and after intranasal immunization of mice. MVA-F administered by intraperitoneal route in a homologous scheme elicited levels of neutralizing antibodies similar to those obtained with inactivated BRSV as well as better levels of IFN-γ secretion. In addition, nasal administration of MVA-F elicited local and systemic immunity with a Th1 profile. This study suggests that MVA-F is a good candidate for further evaluations combining intranasal and intramuscular routes, in order to induce local and systemic immune responses, to improve the vaccine efficacy against BRSV infection., (Copyright © 2023 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.)