Double Vaccination Research Articles

Response to COVID-19 Vaccines in Patients Receiving Intensified Post-ASCT Therapy with Daratumumab, Lenalidomide, Bortezomib (Dara-VR) Due to Ultra-High Risk (UHiR) Newly Diagnosed Myeloma (NDMM) or Primary Plasma Cell Leukemia (pPCL): Exploratory Analysis of the UK Optimum/Muknine Trial

Background: Successful vaccination against SARS-CoV2 is highly effective in preventing serious COVID-19 illness and is particularly recommended for at risk populations including patients with multiple myeloma (MM). However, there is uncertainty to which extent modern intensified therapies targeting plasma cell features might attenuate vaccination responses; some early vaccination recommendations for MM have proposed extended treatment breaks of several weeks to maximise vaccination success. Such an approach can be challenging in UHiR MM and pPCL, where maintaining treatment intensity is hallmark for preventing rapid relapse of the aggressive tumor. To address this uncertainty, we measured post-vaccination serological responses in patients treated uniformly with intensified Dara-VR consolidation and Dara-R maintenance post-ASCT for UHiR NDMM or pPCL in the UK OPTIMUM/MUKnine trial (NCT03188172).Methods: Between Sep 2017 and Jul 2019, 107 patients with UHiR NDMM or pPCL were recruited to OPTIMUM and received intensified post-ASCT consolidation with Dara-VR(d) for 18 cycles followed by maintenance with Dara-R until progression. In an exploratory analysis, centrally stored serum samples available for patients with a completed and documented vaccination history of two doses of an anti-SARS-CoV2 vaccine were analyzed for serological vaccine responses Total IgG/IgA/IgM Anti-SARS-CoV-2 spike glycoprotein was measured by ELISA (MK654; The Binding Site). As per UK national guidance and local availability, patients received two vaccine doses 12 weeks apart of either tozinameran (Pfizer/Biontech) or vaxzevria (AstraZeneca); serum taken at least 3 weeks after patients received their second dose was analyzed. Results were correlated with baseline characteristics and annotated with treatment and response data. Patient with available matched serological and vaccination status data at time of data cut-off (09 JUL 2021) were included. Collection of vaccination status data is ongoing and updated results comprising additional patients enrolled in OPTIMUM, as well as antigen levels, will be presented. Data will also comprise longitudinal antibody level measurements for patient with available sequential material.Results: Serological vaccine response data was available for 40 OPTIMUM patients with documented completed double vaccination status. Median patient age was 58.5 years (range 39-70) and clinical and molecular tumor features were similar to the overall trial safety population. All patients had received their second dose before June 2021. Of the 40 patients, 42.5% had received tozinameran and 57.5% vaxzevria. Baseline characteristics of the two groups were comparable. At time of second vaccine dose, 55% of patients were receiving Dara-VR consolidation treatment and 45% Dara-R maintenance. There was no recommendation to pause trial treatment for purposes of vaccination and no extended times off treatment for this reason were reported. Overall, 72.5% of patients had a positive vaccine antibody level as per manufacturer cut-point for high specificity evidence of antigen exposure (infection or vaccine). The response rate was nominally higher for vaxzevria (91.3%) than for tozinameran (47.1%), a dysbalance that will be further investigated with ongoing extension of the cohort. Of note, 90% of patients analyzed had reached a complete response (CR) of their MM prior to being vaccinated, and the majority of patients not in CR had a positive vaccine response. Response rates were nominally slightly higher in patients in receipt of Dara-R maintenance at time of second dose with 77.8% compared to Dara-VR consolidation with 68.2%.Conclusions: These results show a high serological response rate to COVID-19 vaccination in UHiR MM patients receiving intensified post-ASCT consolidation and maintenance therapy in remission. Findings suggest that continuation of intensified post-ASCT therapy for patients with aggressive tumors and a high risk of relapse are compatible with serological responses to commonly used COVID-19 vaccines. DisclosuresJenner: Janssen: Consultancy, Honoraria, Speakers Bureau; BMS/Celgene: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy; Pfizer: Consultancy. Hall: BMS/Celgene: Research Funding; Janssen: Research Funding. Garg: University Hospital Leicester: Current Employment; Takeda Janssen Novartis Sanofi: Other: Travel Accommodations, Expenses; Amgen Janssen Novartis Sanofi Takeda: Honoraria. Jackson: J and J: Consultancy, Honoraria, Speakers Bureau; GSK: Consultancy, Honoraria, Speakers Bureau; takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; amgen: Consultancy, Honoraria, Speakers Bureau; celgene BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; oncopeptides: Consultancy; Sanofi: Honoraria, Speakers Bureau. Pratt: Binding Site: Consultancy; BMS/Celgene: Consultancy; Gilead: Consultancy; Janssen: Consultancy; Takeda: Consultancy; Amgen: Consultancy. Cook: Karyopharm: Consultancy; Sanofi: Consultancy; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; BMS/Celgene: Consultancy, Research Funding; Amgen: Consultancy. Drayson: Abingdon Health: Current holder of individual stocks in a privately-held company. Kaiser: BMS/Celgene: Consultancy, Other: Travel support, Research Funding; Janssen: Consultancy, Other: Educational support, Research Funding; GSK: Consultancy; Karyopharm: Consultancy, Research Funding; Pfizer: Consultancy; Amgen: Honoraria; Seattle Genetics: Consultancy; Takeda: Consultancy, Other: Educational support; AbbVie: Consultancy.

COVID-19 Vaccination Imperatives in People on Maintenance Dialysis: An International Perspective.

COVID-19 Vaccination Imperatives in People on Maintenance Dialysis: An International Perspective.

Inactivated vaccine against Aujeszky's disease.

Background and Aim:The Aujeszky’s disease, also known as Pseudorabies, remains one of the most problematic fulminant diseases in domestic animals, affecting the central nervous system. The study aimed to investigate the effect of an inactivated vaccine against Aujeszky’s disease based on “Kordai” virus strain.Materials and Methods:To test the inactivation of the “Kordai” strain (grown by the roller method in VNK-21/13 cell culture with an infectious titer of at least 7.5 lg TCD50/ml) which is causative of Aujeszky’s disease, next-generation teotropin and propolis preparations were usedin concentrations of 0.1%, 0.08%, and 0.04%.Results:As a result of comparative studies on the optimization of parameters for inactivating the “Kordai” virus strain, it was established that teotropin is a more effective inactivant than propolis. At the same time, the optimal final concentration of teotropin for inactivation was 0.1%, along with a reaction medium temperature of 37°C, pH of 7.4-7.6, and duration of inactivation of 14 h. The titer of virus-neutralizing activity (VNA) of antibodies at the pH (neutralization reactions) in vaccinated sheep of 10-12 months of age was 7.5±0.3, Ig TCID50/ml (tissue culture infectious dose 50%), and 3.5±0.3 in the cell culture VNK-21/13 (culture of Syrian hamster kidney cells).Conclusion:To determine colostral immunity in newborn lambs, the method of metabolic status correction was used to vaccinate lambs obtained from immune sheep 4 months after birth. The results showed that lambs obtained from immune sheep had high VNA titers. A sustained immune response in vaccinated animals was obtained after double vaccination.

Anti–SARS-CoV-2 Antibody Responses in Patients With IBD Treated With Biologics: Are We Finding CLARITY?

Anti–SARS-CoV-2 Antibody Responses in Patients With IBD Treated With Biologics: Are We Finding CLARITY?

Una sola dósis de BNT162b2 protege contra SARS-CoV-2: Reporte de un caso en un grupo familiar de COVID-19

Background. Coronavirus 2019 (COVID-19) disease is an infectious disease caused by the virus "Severe Acute Respiratory Syndrome Coronavirus 2" (SARS-CoV-2). This virus generated a pandemic in 2020 and has affected millions of people worldwide. Facing the need to prevent its contagion, the vaccine BNT162b2 was approved in December 2020 in Mexico and started administered in healthcare workers. Case presentation. We presented here, two healthcare workers vaccinated with one single dose of BNT162b2, who lives in a family nucleus with high transmission rate of SARS-CoV-2. These healthcare workers, identified in the manuscript as patient E and F, were asymptomatic and their real-time RT-PCR test for SARS-CoV-2 resulted negative, while the rest of the family (patients A-D) were SARS-CoV-2 positive. The antibody titers IgG anti-spike of patient F (after the second dose; 1080 Au/mL) turned out greater than patient E (before the second dose; 37.1 Au/mL). Discussion. To our knowledge this is the first case report of the protective effect of single BNT162b2 vaccine dose in the context of high transmission rates within a family nucleus. Despite changes induced by BNT162b2 in the antibody titers with single or double dose vaccination, a single dose of BNT162b2 showed to be sufficient for immunization of patients against COVID-19.

Mathematical analysis of a measles transmission dynamics model in Bangladesh with double dose vaccination

Although the availability of the measles vaccine, it is still epidemic in many countries globally, including Bangladesh. Eradication of measles needs to keep the basic reproduction number less than one (mathrm{i}.mathrm{e}. , , {mathrm{R}}_{0}<1). This paper investigates a modified (SVEIR) measles compartmental model with double dose vaccination in Bangladesh to simulate the measles prevalence. We perform a dynamical analysis of the resulting system and find that the model contains two equilibrium points: a disease-free equilibrium and an endemic equilibrium. The disease will be died out if the basic reproduction number is less than one (mathrm{i}.mathrm{e}. , , {mathrm{ R}}_{0}<1), and if greater than one (mathrm{i}.mathrm{e}. , , {mathrm{R}}_{0}>1) epidemic occurs. While using the Routh-Hurwitz criteria, the equilibria are found to be locally asymptotically stable under the former condition on {mathrm{R}}_{0}. The partial rank correlation coefficients (PRCCs), a global sensitivity analysis method is used to compute {mathrm{R}}_{0} and measles prevalence left({mathrm{I}}^{*}right) with respect to the estimated and fitted model parameters. We found that the transmission rate (upbeta ) had the most significant influence on measles prevalence. Numerical simulations were carried out to commissions our analytical outcomes. These findings show that how progression rate, transmission rate and double dose vaccination rate affect the dynamics of measles prevalence. The information that we generate from this study may help government and public health professionals in making strategies to deal with the omissions of a measles outbreak and thus control and prevent an epidemic in Bangladesh.

Safety and immunogenicity of a QazCovid-in® inactivated whole-virion vaccine against COVID-19 in healthy adults: A single-centre, randomised, single-blind, placebo-controlled phase 1 and an open-label phase 2 clinical trials with a 6 months follow-up in Kazakhstan.

BackgroundA new inactivated whole-virion QazCovid-in® vaccine against COVID-19 was developed from SARS-CoV-2 isolated in Kazakhstan, inactivated by formaldehyde, and adjuvanted with aluminium hydroxide. Phase 1 and 2 clinical trials aimed at assessing the vaccine's safety, immunogenicity, and the duration of immunity induced by the QazCovid-in® vaccine after one or two immunisations.MethodsFrom 23.09.2020 to 19.03.2021 we performed a randomised, single-blind, placebo-controlled phase 1 clinical trial and from 18.10.2020 to 17.04.2021 an open-label phase 2 clinical trials of the QazCovid-in® vaccine with a 6 months follow-up at a single centre in Almaty, the Republic of Kazakhstan. Eligible healthy adults aged 18 years and older with no history of laboratory-confirmed SARS-CoV-2 infection were randomly assigned to the treatment groups using a computerised randomisation scheme generator. In the phase 1 clinical trial, two doses of the vaccine (5 μg each) or placebo (0·9% NaCl) were administered intramuscularly to 44 subjects aged 18–50 years, 21 days apart. In the phase 2 trial, 200 healthy participants were randomised into four equal-sized groups according to the age (18–49 or ≥50 years) and either single (day 1) or double (day 1 and 21) vaccination protocol. The primary outcomes were safety and tolerability. The secondary outcome was immunogenicity. The cellular response was measured by a whole-blood cytokine release assay (phase 1 only). The trials were registered with ClinicalTrials.gov NCT04530357.FindingsThe QazCovid-in® vaccine was safe and well-tolerated and induced predominantly mild adverse events; no serious or severe adverse events were recorded in both trials. In the phase 1 trial, the percentage of subjects with a fourfold increase of antibody titres (sero conversion) in MNA was 59% after one vaccine dose and amounted to 100% after two doses. Neutralizing antibody titres reached the geometric mean titre (GMT) of 100 after administration of two doses. A statistically significant increase in the levels of pro-inflammatory cytokines after vaccination indicated the Th1-biased response. On day 180, 40% of placebo-treated subjects demonstrated a statistically significant increase in the levels of antibodies measured by both ELISA and MNA, which suggests the infection with SARS-CoV-2. In the phase 2 trial, 100% of subjects aged 18–49 years seroconverted for SARS-CoV-2 on day 21 after the first dose, as indicated by MNA yielding the GMTs of 32 or 30 in the one- and two-dose groups, respectively. Amongst ≥50-year-old subjects, the number of sero conversions in the two- and one-dose groups on day 21 was 94% and 92% with the respective GMTs of 25 and 24. After the second dose, the sero conversion rate reached 100%; however, the GMT was significantly lower when compared with the corresponding value measured in subjects aged 18–49 years (83 vs 143). In both trials, specific antibodies were detected in MNA and ELISA on study day 180, but the titres dropped in comparison to day 42. The results of this study serve as the rationale for the phase 3 study.InterpretationThe QazCovid-in® vaccine is safe and well-tolerated and promotes pronounced humoral immunity which lasts for at least 6 months after double intramuscular immunisation.FundingThe work was funded by the Science Committee of the Ministry of Education and Science of the Republic of Kazakhstan within the framework of the Scientific and Technical Program "Development of a vaccine against coronavirus infection COVID-1900 . State registration number ?.0927.

Walking down the memory lane with SARS-CoV-2 B cells.

The B-cell response to COVID-19 vaccines in convalescent individuals.

Coenzyme Q10 and Vitamin D Interventions Could Ameliorate COVID-19 Related Cellular Bioenergetic Dysfunction and Cytokine Storms

The immune response to SARS-CoV-2 varies from asymptomatic or mild symptoms of high temperature, muscle aches and coughs lasting 7 to 14 days to lower respiratory tract infections leading to pneumonia and serious respiratory distress as well as long COVID-19. Complications occur due to an abnormal immune response which involves upregulation of multiple cytokines leading to sustained inflammation which results in the spread of infection to vital organs. The double vaccine roll out has been rapid however vaccine mediated antibodies are not 100% effective against future coronavirus variants which may become increasingly more resistant and easily transmissible to overcome host immunity. Invariably supportive therapies will be needed. Research has shown that coenzyme Q10 and vitamin D deficiencies can have detrimental effects on immune cell defence, function and cytokine secretion promoting inflammation and sepsis especially against microbes. Early interventions including supplementation of these factors could mitigate cellular dysfunction especially in relation to mitochondria bioenergetics and help maintain cell immunity. This is particularly important as chronically ill COVID-19 patients seem to display abnormal immune cell phenotypes in infected organs indicating this could contribute to disease progression. The immune response and proposed roles of Vitamin D and Coenzyme Q10 in COVID-19 are discussed.

Partial protection of Sinopharm vaccine against SARS COV2 during recent outbreak in Bahrain

BackgroundIn order to impart immunity against SARS COV 2 in the community, the oil rich countries of the Gulf Cooperation Council (GCC) provided citizens and expatriates with free vaccination. Different types of vaccination brands were utilized for this purpose. The purpose of this study is to determine the efficacy of the different types of vaccinations used. MethodsThis is an observational analytical case study of one Bahraini family who were vaccinated with 1st, 2nd or no dose. ResultsOut of 22 double dose recipients of SARS COV2 vaccine, 20 were infected. Those 20 were vaccinated against SARS COV 2 using Sinopharm, the rest (2) were in direct contact with the source but were vaccinated against SARS COV 2 using other type of vaccine. Out of 26 single dose recipients of Sinopharm vaccine, 23 were infected. The other three were not in direct contact with the infected source. Social gathering has been the main source of transmission. The infection has been mild with headache, chest pain. From 20 cases with double dose vaccinations only one had a lung infection and needed hospitalization. Out of 23 cases with single dose vaccinations 10 were hospitalized due to lung infections. All family members who were not vaccinated were infected, three were hospitalized one of which was deceased due to diabetes mellitus complications. ConlcusionSinopharm provides partial protection against SARS COV 2 infection. That might be due to lack of its potential to detect recent variations in the protein structure of spike(S) protein of virus.

Humoral and Cellular Immune Responses Against Severe Acute Respiratory Syndrome Coronavirus 2 Variants and Human Coronaviruses After Single BNT162b2 Vaccination.

BackgroundVaccine-induced neutralizing antibodies are key in combating the coronavirus disease 2019 (COVID-19) pandemic. However, delays of boost immunization due to limited availability of vaccines may leave individuals vulnerable to infection and prolonged or severe disease courses. The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC)—B.1.1.7 (United Kingdom), B.1.351 (South Africa), and P.1 (Brazil)—may exacerbate this issue, as the latter two are able to evade control by antibodies.MethodsWe assessed humoral and T-cell responses against SARS-CoV-2 wild-type (WT), VOC, and endemic human coronaviruses (hCoVs) that were induced after single and double vaccination with BNT162b2.ResultsDespite readily detectable immunoglobulin G (IgG) against the receptor-binding domain of the SARS-CoV-2 S protein at day 14 after a single vaccination, inhibition of SARS-CoV-2 S-driven host cell entry was weak and particularly low for the B.1.351 variant. Frequencies of SARS-CoV-2 WT and VOC-specific T cells were low in many vaccinees after application of a single dose and influenced by immunity against endemic hCoV. The second vaccination significantly boosted T-cell frequencies reactive for WT and B.1.1.7 and B.1.351 variants.ConclusionsThese results call into question whether neutralizing antibodies significantly contribute to protection against COVID-19 upon single vaccination and suggest that cellular immunity is central for the early defenses against COVID-19.

A Novel E2 Glycoprotein Subunit Marker Vaccine Produced in Plant Is Able to Prevent Classical Swine Fever Virus Vertical Transmission after Double Vaccination.

The efficacy of a novel subunit vaccine candidate, based in the CSFV E2 glycoprotein produced in plants to prevent classical swine fever virus (CSFV) vertical transmission, was evaluated. A Nicotiana benthamiana tissue culture system was used to obtain a stable production of the E2-glycoprotein fused to the porcine Fc region of IgG. Ten pregnant sows were divided into three groups: Groups 1 and 2 (four sows each) were vaccinated with either 100 μg/dose or 300 μg/dose of the subunit vaccine at 64 days of pregnancy. Group 3 (two sows) was injected with PBS. Groups 1 and 2 were boosted with the same vaccine dose. At 10 days post second vaccination, the sows in Groups 2 and 3 were challenged with a highly virulent CSFV strain. The vaccinated sows remained clinically healthy and seroconverted rapidly, showing efficient neutralizing antibodies. The fetuses from vaccinated sows did not show gross lesions, and all analyzed tissue samples tested negative for CSFV replication. However, fetuses of non-vaccinated sows had high CSFV replication in tested tissue samples. The results suggested that in vaccinated sows, the plant produced E2 marker vaccine induced the protective immunogenicity at challenge, leading to protection from vertical transmission to fetuses.

Three vs Four Dose Schedule of Double Strength Recombinant Hepatitis-B Vaccine in HIV-infected Children: A Randomized Controlled Trial

To compare seroprotection rates and the anti-HBs titers following primary immunization with double strength (20 µg) recombinant hepatitis B virus (rHBV) vaccine administered intramuscularly (IM) in a 3-dose (0, 1 and 6 months) vs 4-dose (0, 1, 2 and 6 months) schedule in HIV-infected children receiving antiretroviral therapy (ART). An accelerated 3-dose schedule (0, 1, 2 months) within the 4-dose group was also compared. Randomized controlled trial. Pediatric ART clinic of a tertiary hospital in Delhi from November, 2017 to April, 2019. Fifty (25 per group) HIV-infected children aged 18 months - 12 years receiving ART for at least 6 months who had not received any prior dose of HBV vaccine, and were anti-HBs negative. Group 1 received 20 µg of rHBV vaccine IM (in deltoid muscle) at 0, 1, and 6 months, and group 2 received 20 µg the same vaccine at 0, 1, 2 and 6 months. Anti-HBs titers and proportion of responders in 3-dose vs 4-dose group at seventh and twelfth month and at third month after an accelerated 3-dose schedule. Median (IQR) anti-HBs titers at the seventh month were significantly higher in group 2 [225.7 (151-300) IU/L] compared to group 1 [138.2 (35.2-250) IU/L], but were comparable at the 12th month. Seroprotection rates were comparable between group 2 and group 1 at 7th month (96% vs 80%; P=0.19) and 12th month (96% vs 88%; P=0.61). The proportion of good responders were also comparable between the groups at 7th month and 12th month (both P=0.29). Accelerated 3-dose schedule achieved comparable anti-HBs titers [179.9 (130.6-250) IU/L] and seroprotection rate (92%) one month after completion of schedule to the standard 3-dose + schedule. A 3-dose double strength recombinant HBV vaccine schedule offers comparable seroprotection to 4-dose schedule for HIV-infected children receiving ART.

A single vaccination with four-segmented Rift Valley fever virus prevents vertical transmission of the wild-type virus in pregnant ewes

Rift Valley fever virus (RVFV) is a mosquito-transmitted bunyavirus that causes severe outbreaks among wild and domesticated ruminants, of which sheep are the most susceptible. Outbreaks are characterised by high mortality rates among new-born lambs and abortion storms, in which all pregnant ewes in a flock may abort their foetuses. In endemic areas, Rift Valley fever (RVF) can be controlled by vaccination with either inactivated or live-attenuated vaccines. Inactivated vaccines are safe for animals during all physiological stages, including pregnancy. However, optimal efficacy of these vaccines depends on multiple vaccinations and yearly re-vaccination. Live-attenuated vaccines are generally highly efficacious after a single vaccination, but currently available live-attenuated vaccines may transmit to the ovine foetus, resulting in stillbirths, congenital malformations or abortion. We have previously reported the development of a novel live-attenuated RVFV vaccine, named RVFV-4s. This vaccine virus was created by splitting the M genome segment and deleting the major virulence determinant NSs, and was shown to be safe even for the most susceptible species, including pregnant ewes. The demonstrated efficacy and safety profile suggests that RVFV-4s holds promise for veterinary and human application. The RVFV-4s vaccine for veterinary application, here referred to as vRVFV-4s, was shown to provide complete protection after a single vaccination of lambs, goats and cattle. In this work, we evaluated the efficacy of the vRVFV-4s vaccine in pregnant ewes. Anticipating on the extremely high susceptibility of pregnant ewes for RVFV, both a single vaccination and double vaccination were evaluated in two independent experiments. The combined results suggest that a single vaccination with vRVFV-4s is sufficient to protect pregnant ewes and to prevent transmission to the ovine foetus.

Эпидемиологическая и социально-экономическая оценка эффективности программы однократной вакцинации против ветряной оспы детей 6 лет на примере Алтайского края

Introduction. Chickenpox is one of the most common and highly contagious infections. Since the domestic vaccine has not been developed at the moment, and the purchase of an imported vaccine for routine vaccination is an expensive investment of the state, there is a need to assess the epidemiological and socio-economic effectiveness of vaccination. Purpose: to evaluate the epidemiological and socio-economic effectiveness of a single vaccination program against chickenpox in children aged 6 years on the example of the Altai Territory. Materials and methods. The materials were the reporting forms No. 2 of the Federal State Statistical Observation "Information on infectious and parasitic diseases" in the city of Barnaul for 2001-2019. The economic assessment was carried out on the basis of MU 3.3.1878-04 of 04.03.2004 "Economic efficiency of vaccination". The method of simulation modeling was used to assess the epidemiological effectiveness. Results. The cost of treating chickenpox is almost twice the cost of a vaccination program. The self-sufficiency of vaccination of a cohort of children 6 years of age against chickenpox, carried out in 2021, will be achieved during 2031, and in the future, the damage prevented will constantly increase. The economic benefit will amount to about 7.52 million rubles, and the prevented damage will exceed the costs by 1.2 times. The epidemiological effectiveness of vaccination is observed after five years of the program implementation, the incidence decreases 2-2.5 times. Conclusions. Taking into account the data of literary sources, it is advisable to vaccinate children according to the program of double cohort vaccination with the introduction of the first dose of the vaccine at 12 months and the second dose at 6 years. However, in regions such as the Altai Territory, where previously there was no vaccination of chickenpox, at the initial stage of implementation it is necessary to vaccinate children over 6 years of age in order to prevent the "maturation" of the infection.

Hybrid Immunity Versus Vaccine-Induced Immunity Against SARS CoV2 in Patients With Autoimmune Rheumatic Diseases

Introduction: Single-dose COVID-19 vaccines in healthy individuals with past COVID-19 infections seem to provide better immunity than double doses in COVID-19 unexposed individuals. However, it is not known whether the same is true for patients with autoimmune rheumatic diseases (AIRD) who are on immunosuppressants.Methods: We identified 30 patients with AIRD who took a single dose of the ChAdOx1 vaccine post-COVID-19 infection. Age, sex and disease similar patients were enrolled in to three groups of 30 each who had (1) past infection with COVID-19 but no vaccine, (2) a single dose of ChAdOx1 and (3) double doses of ChAdOx1. Sera were collected from each patient approximately 30 days after last vaccine dose or since the onset of COVID19 symptoms (in the unvaccinated group). Antibodies to spike protein were estimated and virus neutralization potential of sera was tested.Results: Baseline characteristics including drug usage was similar between the groups. Seroconversion occurred in 25(83%), 23(77%), 27(90%), and 30(100%) in natural infection, single-dose vaccine, double dose vaccine, and infection +single dose vaccine groups respectively. Mean antibody titres (10076.8±8998) in the last group were at least 6-100x higher than in the other 3 groups. Also, the infection +vaccine group had the highest neutralization potential of 83.37 % as compared to 45.4% in the fully vaccinated group.Conclusion: The hybrid immunity with a single dose of the vector-based vaccine post-infection seems to be superior to double dosage of the vaccine in patients with AIRD. A universal vaccination strategy involving a single dose of vaccine for all individuals with previous COVID-19 infection seems to be effective in these patients also.

Feasibility and efficiency of probiotics, antibiotics and vaccines in associated bacterial infectious diseases in cattle

The article presents the results of determining the feasibility and efficiency of the vaccine for the prevention of associated diseases in a farm with a high level of animal morbidity and the circulation of multidrug-resistant pathogens. The incidence of pneumoenteritis in calves was 38.0%, the incidence of various forms of mastitis and endometritis in cows was 48.2% and 76.2%, respectively. The causative agents of escherichiosis (Escherichia coli), staphylococcosis (Staphylococcus aureus), anaerobic enterotoxemia (Clostridium perfringens), and a number of opportunistic pathogens that were involved in complicating the associated course of the disease, were isolated from sick animals. The isolated microflora was resistant to penicillin drugs, aminoglycosides, macrolides, amphenicols, lincosamides, cephalosporins and even to some fluoroquinolones. In addition, it was found that probiotic cultures of the genus Bacillus had more pronounced antagonistic activity against isolated pathogens, so it is advisable to use them in disease outbreaks to displace pathogenic microflora from the source of infection. In the prevention of the disease and for normalization of the microflora after the use of antibacterial drugs, it is advisable to use probiotics based on lactobacilli, as they have the highest adhesion (from 6.4 ± 0.6 to 8.9 ± 0.4). Vaccination has contributed to a decrease in animal morbidity. The incidence in vaccinated cows was lower than in the control group, in particular the incidence of mastitis was lower by 15–25%; manure retention — by 15–32.7%, endometritis — by 17–30%. Double vaccination of dry cows provides the formation of colostral immunity in calves and 20% decrease in the incidence of respiratory and gastrointestinal diseases in calves. In addition, vaccination of cows helped to improve the quality of milk by the degree of its contamination with bacterial microflora

Efficacy of a turkey herpesvirus double construct vaccine (HVT-ND-IBD) against challenge with different strains of Newcastle disease, infectious bursal disease and Marek’s disease viruses

ABSTRACT A double construct vaccine of turkey herpesvirus (HVT) was prepared that contains the fusion (F) gene from Newcastle disease virus (NDV) and the viral protein 2 (VP2) gene from infectious bursal disease virus (IBDV). Safety of the vaccine (HVT-ND-IBD) was confirmed and efficacy was evaluated after subcutaneous (SC) vaccination at 1 day of age or the in ovo route of vaccination. Challenges were performed with velogenic NDV strains (Texas GB and Herts Weybridge 33/56), with different strains of IBDV (classical strain STC; very virulent strain CS89 and variant E strain) and with Marek’s disease virus (MDV) strain RB1B. Vaccination with HVT-ND-IBD induced a high level of protection against these challenges. Vaccination with HVT is often combined with Rispens CVI988 vaccine and live ND vaccines for higher and earlier, MD and ND protection, respectively. HVT-ND-IBD vaccination in combination with these vaccines showed MD protection as early as 4 days post vaccination and ND protection as early as 2 weeks post vaccination. The long protection as seen with HVT vaccination was confirmed by demonstrating protection against NDV up to 60 weeks. Finally, to evaluate the performance of the vaccine in commercial birds with maternally-derived antibodies, two field trials were performed, using in ovo vaccination in broilers and SC vaccination in combination with Rispens CVI988 vaccine in layer-type birds. The efficacy was confirmed for all components by challenges. These results demonstrate that HVT-ND-IBD is a safe and highly efficacious vaccine for simultaneous control of ND, IBD and MD. RESEARCH HIGHLIGHTS A double construct HVT vaccine with the NDV F and the IBDV VP2 genes was prepared. The vaccine protects against three important diseases: MDV, NDV and IBDV. In ovo and sub-cutaneous vaccination was evaluated in the field in commercial chickens.

Estimation of the Potential Benefits of Meningococcal Vaccination in Children at 9 and 12 Months of Age Using a Predictive Mathematical Model

Relevance. To address the issue of including vaccines against meningococcal infection (MI) in the Russian National Immunization Schedule (NIS), convincing arguments must be presented that demonstrate not only epidemiological, but also economic benefits.Aim of this study was conducted to confirm them.Materials &amp; methods. For calculating epidemiological consequences, a dynamic predictive simulation model was constructed to compare the potential epidemiological burden of the disease in the current vaccination scenario (no MI vaccination in the NIS) and a new scenario involving vaccination of children aged 9 and 12 months with the MenACWY-d vaccine. The epidemiological outlook for meningococcal infection was assessed based on the dynamics of the main indicators of its prevalence in the General population that developed in previous years, taking into account the impact of double vaccination of children at 9 and 12 months on the survival period of each age cohort vaccinated in 2019–2034. The aim is to assess the predicted socio-economic consequences for different scenarios: while maintaining the current vaccination algorithm and including in the NIS vaccination against MI of all children aged 9 and 12 months using mathematical modeling.Results and discussion. The greatest impact on reducing the number of clinical cases of the disease will be achieved in the age cohorts 0–1 years (-89%), 1–2 years (-84.5%), 3–6 years (-73.6%). Model calculations show that due to double vaccination of children under one year of age, 571 deaths can be expected to be prevented by 2034, which is equivalent to a reduction in losses of 40,509 years of life ahead and a social gain of 104.7 billion rubles in the monetary equivalent of the cost of these years (cumulative total). At the same time, taking into account the prevented cases of the disease, the total monetary equivalent of the benefits of society will begin to exceed the cost of vaccination earlier than in four years.Conclusions thus, even an underestimated estimate of benefits that does not take into account the total amount of damage prevented (prevention of 571 deaths, loss of 40,509 years of life and 104.7 billion rubles in monetary terms of the cost of years of life to come), indicates the obvious importance of expanding the NIS and including vaccination of children aged 9 and 12 months from meningococcal infection.

The efficiency of vaccination against cattle necrobacteriosis using an experimental vaccine with a new adjuvant complex

The purpose of the study was to analyze the effectiveness of the adjuvant complex based on saponin, glycerin and chitosan in the experimental series of an inactivated vaccine against cattle necrobacteriosis. 4 groups of animals (30 in each group) were selected for the study, aged 6 to 24 months. The first (1st) group consisted of calves 6 months old, the second (2nd) group consisted of animals 12 months old and the third group – animals 24 months old. The control 4 (fourth) group (non-vaccinated animals) contained 10 animals of each age group – 6, 12 and 24 months old. The animals were vaccinated using a needle-free injector at a dose of 0.4 cm3 in two points at a distance of 7–10 cm (0.2 cm3 each) twice at intervals of 4-6 weeks. Revaccinated after 6 months, with a single dose of 0.4 cm3 (at two points, 0.2 cm2 each). It was found that the vaccine with the multicomponent adjuvant had low viscosity and hardening temperature, moderate reactivity, high stability during storage, prolonged immunity in vaccinated animals. The immunity in animals was detected 21 days after the first vaccine administration and lasted at least 18 months after the last immunization. The necrobacteriosis incidence in animals of the control non-vaccinated group was 70-80%. During double vaccination, the average level of postvaccinal agglutinating antibodies in serum of experimental groups of animals was 312.08±74.12 – 62.13±69, 07. Humoral response in vaccinated animals provided reliable protection against Fusobacterium necrophorum disease within two years (observation period). Absence of disease symptoms in vaccinated animals during 2 years testified to the high preventive efficiency of the vaccine. The results obtained confirm the validity of the application of multicomponent adjuvant in inactivated sorbed vaccine as a means of specific prevention of animal necrobacteriosis.