7 research outputs found
SPUTNIK-V REACTOGENICITY AND IMMUNOGENICITY IN THE BLOOD AND MUCOSA: A PROSPECTIVE COHORT STUDY
Sputnik-V (Gam-COVID-Vac) is a heterologous, recombinant adenoviral (rAdv) vector-based, COVID-
19 vaccine now used in > 70 countries. Yet there is a shortage of data on this vaccine’s performance in
diverse populations. Here, we performed a prospective cohort study to assess the reactogenicity and
immunologic outcomes of Sputnik-V vaccination in Kazakhstan. COVID-19-free participants (n = 82 at
baseline) were followed at day 21 after Sputnik-V dose 1 (rAd5) and dose 2 (rAd26). Self-reported local
and systemic adverse events were captured using questionnaires. Blood and nasopharyngeal swabs
were collected to perform SARS-CoV-2 diagnostic and immunologic assays. We observed that most
of the reported adverse events were mild-to-moderate injection site or systemic reactions, no severe
or potentially life-threatening conditions were reported, and dose 1 appeared to be more reactogenic
than dose 2. The seroconversion rate was 97% post-dose 1, remaining the same post-dose 2. The
proportion of participants with detectable virus neutralization was 83% post-dose 1, increasing to
98% post-dose 2, with the largest relative increase observed in participants without prior COVID-
19 exposure. Dose 1 boosted nasal S-IgG and S-IgA, while the boosting effect of dose 2 on mucosal
S-IgG, but not S-IgA, was only observed in subjects without prior COVID-19. Systemically, vaccination
reduced serum levels of growth regulated oncogene (GRO), which correlated with an elevation
in blood platelet count. Overall, Sputnik-V dose 1 elicited both blood and mucosal SARS-CoV-2
immunity, while the immune boosting effect of dose 2 was minimal. Thus, adjustments to the current
vaccine dosing regimen are necessary to optimize immunization efficacy and cost-effectiveness. While
Sputnik-V reactogenicity is similar to that of other COVID-19 vaccines, the induced alterations to the
GRO/platelet axis warrant investigation of the vaccine’s effects on systemic immunology
Beta-Glucan Particles as a Delivery System in Peptide Vaccine Development
The successful delivery of vaccine antigens such as peptides and proteins to stimulate CD4 and CD8 T cell immunity could provide a prevention or treatment of infectious diseases and malignant disorders. This project tested different strategies of peptide delivery to phagocytic cells using using Beta-glucan particles (GPs), and assayed the in vitro immune-stimulatory capabilities. GPs are hollow microparticles derived from Baker’s yeast that can be used to encapsulate or bind peptide payloads to ensure delivery to target cells. Various synthetic strategies were evaluated to identify an effective delivery method for in vitro testing using a T-cell proliferation assay
Stem Cells and Society
The purpose of this project is to describe the impact of stem cells on society by describing their types, how they are isolated, and their medical benefits, while also investigating the ethical and legal issues surrounding their use. Chapter-1 and Chapter-2 describe different types of stem cells and their sources, and explain various applications of stem cells and how they can contribute to treating different diseases. Chapter-3 and Chapter-4 discuss ethical issues surrounding stem research, and the laws that govern their use. Based on the project research, the authors provide conclusions about the future directions of stem cell research
Detection of Hepatitis E Antibodies in Kazakhstan: A Pilot Study
Introduction. Hepatitis E virus exposure is associated with sporadic cases of acute hepatitis and outbreaks in many countries worldwide. It is particularly dangerous for pregnant women, in whom the mortality rate is high. There are no previously published data reporting circulation of this virus in Kazakhstan.
Methods. We tested blood samples for IgG anti-hepatitis E virus antibodies in 199 Kazakh participants; of these 119 were workers at the EXPO 2017 building site in Astana, 35 were volunteers who got tested at the Astana City Hall on the World Hepatitis Day 2017, and 45 were volunteers who presented for screening at the Hepatogastroenterology Outpatient Clinic of the Republican Diagnostic Center, University Medical Center.
Results. 11 (5.5%) individuals were positive for IgG anti-HEV antibodies, with a higher seroprevalence in males (7; 6.8%) vs females (4; 4.5%). The highest number of positive samples was in the 32-46 years age group.
Conclusions. This pilot study suggests that Hepatitis E virus has been circulating in Kazakhstan. Studies are needed to determine whether it continues to be present, which viral genotypes are involved and what are the best methodologies for preventing its spread
Sustained Delivery of a Monoclonal Antibody against SARS-CoV-2 by Microencapsulated Cells: A Proof-of-Concept Study
Background: Monoclonal antibody (mAb) therapy is a promising antiviral intervention for Coronovirus disease (COVID-19) with a potential for both treatment and prophylaxis. However, a major barrier to implementing mAb therapies in clinical practice is the intricate nature of mAb preparation and delivery. Therefore, here, in a pre-clinical model, we explored the possibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mAb delivery using a mAb-expressing encapsulated cell system. Methods: Murine G-8 myoblasts were transfected with plasmids coding for the heavy and light chains of CR3022, a well-characterized SARS-CoV-2 mAb that targets the Spike receptor binding domain (RBD), and then encapsulated into alginate microcapsules. The microcapsules were then intraperitoneally implanted into immunocompetent (C57/BL6J) mice and changes in circulating CR3022 titres were assessed. The in vitro and ex vivo characterization of the mAb was performed using western blotting, RBD ELISA, and microscopy. Results: Transfected G-8 myoblasts expressed intact CR3022 IgG at levels comparable to transfected HEK-293 cells. Cell encapsulation yielded microcapsules harbouring approximately 1000 cells/capsule and sustainably secreting CR3022 mAb. Subsequent peritoneal G-8 microcapsule implantation into mice resulted in a gradual increase of CR3022 concentration in blood, which by day 7 peaked at 1923 [1656–2190] ng/mL and then gradually decreased ~4-fold by day 40 post-implantation. Concurrently, we detected an increase in mouse anti-CR3022 IgG titers, while microcapsules recovered by day 40 post-implantation showed a reduced per-microcapsule mAb production. Summary: We demonstrate here that cell microencapsulation is a viable approach to systemic delivery of intact SARS-CoV-2 mAb, with potential therapeutic applications that warrant further exploration
HIGH SARS-COV-2 SEROPREVALENCE IN KARAGANDA, KAZAKHSTAN BEFORE THE LAUNCH OF COVID-19 VACCINATION
COVID-19 exposure in Central Asia appears underestimated and SARS-CoV-2 seroprevalence
data are urgently needed to inform ongoing vaccination efforts and other strategies to
mitigate the regional pandemic. Here, in a pilot serologic study we assessed the prevalence
of SARS-CoV-2 antibody-mediated immunity in a multi-ethnic cohort of public university
employees in Karaganda, Kazakhstan. Asymptomatic subjects (n = 100) were recruited
prior to their first COVID-19 vaccination. Questionnaires were administered to capture a
range of demographic and clinical characteristics. Nasopharyngeal swabs were collected
for SARS-CoV-2 RT-qPCR testing. Serological assays were performed to detect spike (S)-
reactive IgG and IgA and to assess virus neutralization. Pre-pandemic samples were used
to validate the assay positivity thresholds. S-IgG and -IgA seropositivity rates among SARSCoV-
2 PCR-negative participants (n = 100) were 42% (95% CI [32.2–52.3]) and 59% (95%
CI [48.8–69.0]), respectively, and 64% (95% CI [53.4–73.1]) of the cohort tested positive for
at least one of the antibodies. S-IgG titres correlated with virus neutralization activity, detectable
in 49% of the tested subset with prior COVID-19 history. Serologically confirmed history
of COVID-19 was associated with Kazakh ethnicity, but not with other ethnic minorities present
in the cohort, and self-reported history of respiratory illness since March 2020. Overall,
SARS-CoV-2 exposure in this cohort was ~15-fold higher compared to the reported all-time
national and regional COVID-19 prevalence, consistent with recent studies of excess infection
and death in Kazakhstan. Continuous serological surveillance provides important
insights into COVID-19 transmission dynamics and may be used to better inform the
regional public health response