Analysing vaccine efficacy evaluated in phase 3 clinical trials carried out during outbreaks

In this paper we examine several definitions of vaccine efficacy(VE)that we found in the literature,for diseases that express themselves in outbreaks,that is,when the force of infection grows in time,reaches a maximum and then vanishes.The fact that the disease occurs in outbreaks results in several problems that we analyse.We propose a mathematical model that allows the calculation of VE for several scenarios.Vaccine trials usually needs a large number of volunteers that must be enrolled.Ideally,all volunteers should be enrolled in approximately the same time,but this is generally impossible for logistic reasons and they are enrolled in a fashion that can be replaced by a continuous density function(for example,a Gaussian function).The outbreak can also be replaced by a continuous density function,and the use of these density functions simplifies the calculations.Assuming,for example Gaussian functions,one of the problems one can immediately notice is that the peak of the two curves do not occur at the same time.The model allows us to conclude:First,the calculated vaccine efficacy decreases when the force of infection increases;Second,the calculated vaccine efficacy decreases when the gap between the peak in the force of infection and the peak in the enrollment rate increases;Third,different trial protocols can be simulated with this model;different vaccine efficacy definitions can be calculated and in our simulations,all result are approximately the same.The final,and perhaps most important conclusion of our model,is that vaccine efficacy calculated during outbreaks must be carefully examined and the best way we can suggest to overcome this problem is to stratify the enrolled volunteer's in a cohort-by-cohort basis and do the survival analysis for each cohort,or apply the Cox proportional hazards model for each cohort.

Chronic social defeat stress‑induced depression reduces BCG efficacy by promoting regulatory T‑cell levels in mice

Despite the initial successes of the Bacillus Calmette-Guerin(BCG)vaccine in children,its efficacy against tuberculosis is highly variable.There is a lack of understanding about how mental conditions influence BCG vaccination.Here,we used the chronic social defeat stress(CSDS)model to explore the effects of depression on BCG vaccination efficacy.We observed higher lung and spleen bacterial loads and a lower organ index in depressed compared to BCG mice.Meanwhile,a relatively lower T cell protective efficacy was observed in both compared to control and BCG mice via a mycobacterium growth inhibition assay(MGIA).Cytokine expression of IL-12p40,IL-1β,IL-17,TNF-αand IFN-γwas reduced,whereas the expression of IL-10 and IL-5 was increased in the spleen of both compared to BCG mice.Moreover,the proportions of CD4^(+)IFN-γ^(+),CD8^(+)IFN-γ^(+)T lymphocytes and CD4^(+)effector/central memory T cells were reduced in the splenocytes of the depressed BCG mice.Depression promotes CD4^(+)regulatory T cells(Treg)and myeloid-derived suppressor cell(MDSC)generation in depressed mice,contributing to the reduced pro-inflammatory immune response upon BCG vaccination.This study provides insight into the decreased protective immunity by BCG vaccination attributable to depression in mice.

Vaccination for solid organ transplanted patients:Recommendations,efficacy,and safety

Solid organ transplant recipients face unique challenges in managing their im-munosuppressed status,making vaccination a critical consideration.This review aimed to comprehensively analyze current recommendations,evaluate the effi-cacy of vaccinations in this population,and assess safety concerns.We explored the latest evidence on vaccine types,timing,and potential benefits for transplant patients,highlighting the importance of individualized approaches for routinely used vaccines as well as coronavirus disease 2019 vaccines.By synthesizing avai-lable data,this review underscored the pressing need to optimize vaccination strategies,ensuring that transplant recipients can obtain the full protection against many pathogens while minimizing risks associated with their post-transplant immunosuppression.

Evaluation of the Protective Efficacy of a Fused OmpK/Omp22 Protein Vaccine Candidate against Acinetobacter baumannii Infection in Mice

Acinetobocter baumannfi （A. Baumannii） is an emerging opportunistic pathogen responsible for hospital-acquired infections, and which now constitutes a sufficiently serious threat to public health to necessitate the development of an effective vaccine. In this study, a recombinant fused protein named OmpK/Omp22 and two individual proteins OmpK and Omp22 were obtained using recombinant expression and Ni-affinity purification. Groups of BALB/c mice were immunized with these proteins and challenged with a clinically isolated strain of A. boumonnii. The bacterial load in the blood, pathological changes in the lung tissue and survival rates after challenge were evaluated. Mice immunized with OmpK/Omp22 fused protein provided significantly greater protection against A. boumonnfi challenge than those immunized with either of the two proteins individually. The results provide novel clues for future design of vaccines against A. boumonnii.

Mathematical modeling for estimating influenza vaccine efficacy:A case study of the Valencian Community,Spain.

Vaccine efficacy and its quantification is a crucial concept for the proper design of public health vaccination policies.In this work we proposed a mathematical model to estimate the efficacy of the influenza vaccine in a real-word scenario.In particular,our model is a SEIR-type epidemiological model,which distinguishes vaccinated and unvaccinated populations.Mathematically,its dynamics is governed by a nonlinear system of ordinary differential equations,where the non-linearity arises from the effective contacts between susceptible and infected individuals.Two key aspects of this study is that we use a vaccine distribution over time that is based on real data specific to the elderly people in the Valencian Community and the calibration process takes into account that over one influenza season a specific proportion of the population becomes infected with influenza.To consider the effectiveness of the vaccine,the model incorporates a parameter,the vaccine attenuation factor,which is related with the vaccine efficacy against the influenza virus.With this framework,in order to calibrate the model parameters and to obtain an influenza vaccine efficacy estimation,we considered the 2016–2017 influenza season in the Valencian Community,Spain,using the influenza reported cases of vaccinated and unvaccinated.In order to ensure the model identifiability,we choose to deterministically calibrate the parameters for different scenarios and we find the one with the minimum error in order to determine the vaccine efficacy.The calibration results suggest that the influenza vaccine developed for 2016–2017 influenza season has an efficacy of approximately 76.7%,and that the risk of becoming infected is five times higher for an unvaccinated individual in comparison with a vaccinated one.This estimation partially agrees with some previous studies related to the influenza vaccine.This study presents a new integrated mathematical approach to study the influenza vaccine efficacy and gives further insight into this important public health topic.

Peptides-based vaccine against SARS-nCoV-2 antigenic fragmented synthetic epitopes recognized by T cell and β-cell initiation of specific antibodies tofightthe infection

The World Health Organization has declared the rapidly spreading coronavirus to be a global pandemic.The FDA is yet to approve a vaccine for human novel coronavirus.Here,we developed a peptide-based vaccine and used high-throughput screening by molecular dynamics simulation to identify T-cell-and p-cell-recognized epitopes for producing specific antibod-ies against SARS-nCoV-2.We construct~12 P'antigenic epitope peptides to develop a more effective vaccine and identify specific antibodies.These epitope peptides selectively presented the best antigen presentation scores for both human pMHC class I and II alleles to develop a strong binding affinity.All antigens identified of SARS-nCoV-2 different proteins by each attached specific~1-7 L linker adaptor were used to construct a broad single peripheral peptide vaccine.It is expected to be highly antigenic with a minimum allergic effect.As a result of these exciting outcomes,expressing a vaccine using the intimated peptide was highly promising and positive to be highly proposed as epitope-based peptide vaccine of specific antibody against SARS-nCoV-2 by initiating T cells and β-cells.An in vitro study for the proposed peptide-based vaccine is.mostly recommended.Further clinical trials are required to check the efficacy of this vaccine.

A Game-Theoretic Modeling Approach to Comprehend the Advantage of Dynamic Health Interventions in Limiting the Transmission of Multi-Strain Epidemics

In the situation of inadequate vaccines and rapid mutation of virulent strains, alternative health interventions play a crucial role in the containment of emerging epidemics. This study elucidates the critical aspects of health interventions to control epidemic resurgence. Besides, human behavioral response to epidemics plays an instrumental role in bringing the success of control efforts. The appearance of multi-strain epidemics has become a global health concern that requires special attention. Here, we introduce a novel mean-field epidemic game approach to predict the evolutionary dynamics of flu-like epidemics having multiple disease strains. Our model illustrates the importance of multiple provisions alongside their timely execution for better disease attenuation. In addition to vaccination, we introduce self-protection as a potential alternative that yields safeguard against either strain. Both these imperfect provisions render better efficacy against primary (resident) strain than secondary (mutant) to contain epidemic transmission. The simulation-backed model analysis further sheds some light on the crucial impacts of control interventions to limit the invasion of virulent strains from qualitative and quantitative viewpoints. It explicates how vaccination and self-protection complement each other as per situation demands. Our full-fledged theoretical approach further illustrates the dynamic trade-off between the cost and efficacy of a certain intervention. We confirm that the disease dies out when the basic reproduction number of individual strains is less than one and becomes endemic if it is greater than one. Finally, the model addresses the evolutionary consequences when mutation takes place from primary to secondary strain. Some impressive facts while employing dual provisions have been reinforced using a game-theoretic framework.

LONG-TERM IMMUNOGENICITY AND EFFICACY OF RECOMBINANT YEAST DERIVED HEPATITIS B VACCINE FOR INTERRUPTION OF MOTHER-INFANT TRANSMISSION OF HEPATITIS B VIRUS

Recombinant DNA Yeast-Derived Hepatitis B Vaccine (RYHB vaccine) is comparable to and can replace Plasma-Derived Hepatitis B Vaccine (PHB vaccine) for the prevention of mother-nfant transmission of hepatitis B virus (HBV), but the duration of immune efficacy of RYHB vaccine is not clear. This study indicates the long-term efficacy for the prevention of mother-infant transmission of HBV. One hundred and six neonates born to HBsAg-arrier mothers with HBeAg positive were randomly divided into two groups, one receiving 20 μg per dose of RYHB vaccine and the another receiving 20 μg per dose of PHB vaccine on the day of birth, at 1 month and at 6 months (three times). Physical examination and blood tests were performed for all infants at 6, 12, 24, 36, 48 and 60 months of age. The results showed that the protective efficacies at 6, 12, 24, 36, 48 and 60 months were 67%, 75%, 63%, 62%, 57% and 56%, respectively for the RYHB vaccine group and 58%, 76%, 51%, 41%, 24% and 18%, respectively for the PHB vaccine group. The protective efficacy was notably significant in the last two years. The study indicates that the duration of protective efficacy is over 5 years with RYHB vaccine, being longer than that of PHB vaccine. These recipients of RYHB vaccine showed no side effects, and the vaccine is regarded as safe and effective.

Non-pharmaceutical interventions and their relevance in the COVID-19 vaccine rollout in Saudi Arabia and Arab Gulf countries

In the early stages of the pandemic,Saudi Arabia and other countries in the Arab Gulf region relied on non-pharmaceutical therapies to limit the effect of the pandemic,much like other nations across the world.In comparison to other nations in the area or globally,these interventions were successful at lowering the healthcare burden.This was accomplished via the deterioration of the economy,education,and a variety of other societal activities.By the end of 2020,the promise of effective vaccinations against SARS-CoV-2 have been realized,and vaccination programs have begun in developed countries,followed by the rest of the world.Despite this,there is still a long way to go in the fight against the disease.In order to explore disease transmission,vaccine rollout and prioritisation,as well as behavioural dynamics,we relied on an age-structured compartmental model.We examine how individual and social behaviour changes in response to the initiation of vaccination campaigns and the relaxation of non-pharmacological treatments.Overall,vaccination remains the most effective method of containing the disease and resuming normal life.Additionally,we evaluate several vaccination prioritisation schemes based on age group,behavioural responses,vaccine effectiveness,and vaccination rollout speed.We applied our model to four Arab Gulf nations(Saudi Arabia,Bahrain,the United Arab Emirates,and Oman),which were chosen for their low mortality rate compared to other countries in the region or worldwide,as well as their demographic and economic settings.We fitted the model using actual pandemic data in these countries.Our results suggest that vaccinations focused on the elderly and rapid vaccine distribution are critical for reducing disease resurgence.Our result also reinforces the cautious note that early relaxation of safety measures may compromise the vaccine's short-term advantages.

The immune response to SARS-CoV-2 in people with HIV

This review examines the intersection of the HIV and SARS-CoV-2 pandemics.People with HIV(PWH)are a heterogeneous group that differ in their degree of immune suppression,immune reconstitution,and viral control.While COVID-19 in those with wellcontrolled HIV infection poses no greater risk than that for HIV-uninfected individuals,people with advanced HIV disease are more vulnerable to poor COVID-19 outcomes.COVID-19 vaccines are effective and well tolerated in the majority of PWH,though reduced vaccine efficacy,breakthrough infections and faster waning of vaccine effectiveness have been demonstrated in PWH.This is likely a result of suboptimal humoral and cellular immune responses after vaccination.People with advanced HIV may also experience prolonged infection that may give rise to new epidemiologically significant variants,but initiation or resumption of antiretroviral therapy(ART)can effectively clear persistent infection.COVID-19 vaccine guidelines reflect these increased risks and recommend prioritization for vaccination and additional booster doses for PWH who are moderately to severely immunocompromised.We recommend continued research and monitoring of PWH with SARS-CoV-2 infection,especially in areas with a high HIV burden.

Impact of mycotoxin on immune response and consequences for pig health

Mycotoxins are fungal secondary metabolites detected in many agricultural commodities, especially cereals. Due to their high consumption of cereals, pigs are exposed to these toxins. In the European Union, regulations and/or recommendations exist in pig feed for aflatoxins, ochratoxin A, fumonisins,zearalenone, and trichothecenes, deoxynivalenol and T-2 toxin. These mycotoxins have different toxic effects, but they all target the immune system. They have immunostimulatory or immunosuppressive effects depending on the toxin, the concentration and the parameter investigated. The immune system is primarily responsible for defense against invading organisms. The consequences of the ingestion of mycotoxin-contaminated feed are an increased susceptibility to infectious diseases, a reactivation of chronic infection and a decreased vaccine efficacy. In this review we summarized the data available on the effect of mycotoxins on the immune system and the consequences for pig health.

The effect of mixed vaccination rollout strategy:A modelling study

Vaccines have measurable efficacy obtained first from vaccine trials.However,vaccine efficacy(VE)is not a static measure and long-term population studies are needed to evaluate its performance and impact.COVID-19 vaccines have been developed in record time and the currently licensed vaccines are extremely effective against severe disease with higher VE after the full immunization schedule.To assess the impact of the initial phase of the COVID-19 vaccination rollout programmes,we used an extended Susceptible-Hospitalized-Asymptomatic/mild-Recovered(SHAR)model.Vaccination models were proposed to evaluate different vaccine types:vaccine type 1 which protects against severe disease only but fails to block disease transmission,and vaccine type 2 which protects against both severe disease and infection.VE was assumed as reported by the vaccine trials incorporating the difference in efficacy between one and two doses of vaccine administration.We described the performance of the vaccine in reducing hospitalizations during a momentary scenario in the Basque Country,Spain.With a population in a mixed vaccination setting,our results have shown that reductions in hospitalized COVID-19 cases were observed five months after the vaccination rollout started,from May to June 2021.Specifically in June,a good agreement between modelling simulation and empirical data was well pronounced.