Lifelong Immunity Research Articles

In silico analysis and structural vaccinology prediction of Toxoplasma gondii ROP41 gene via immunoinformatics methods as a vaccine candidate

IntroductionToxoplasma gondii (T. gondii) infects all warm-blooded animals, including humans. Currently, no effective treatments exist to prevent the generation of chronic tissue cysts in infected hosts. Therefore, developing a vaccine to protect to deal with toxoplasmosis is a promising strategy, as a single immunization could provide lifelong protective immunity. Rhoptry proteins (ROPs) play a vital role for the parasite's survival within host cells and perform critical functions during different phases of parasite invasion. Little is known about ROP41 gene. Nevertheless, Understanding the characteristics of ROP41 will enhance diagnostic and vaccine research. Materials and MethodsThe current article provides a comprehensive analysis of the essential components of the ROP41 protein, including its transmembrane domain, physico-chemical properties, subcellular location, tertiary and secondary structures, and potential T- and B-cell epitopes. These features were determined by many bioinformatics approaches to identify possible epitopes for developing a highly effective vaccine. ResultsROP41 protein showed 36 possible post-translational modification regions. The ROP41 protein secondary structure contains 17.35 % extended strand, 33.47 % alpha-helix, and 49.18 % random coil. Also, ROP41 showed many possible B- and T-cell epitopes. According to the Ramachandran plot, 90.78 % of amino acid residues had been placed in favored, 3.28 % in outlier, and 5.94 % in allowed areas. Also, the allergenicity and antigenicity evaluation indicated that ROP41 is non-allergenic and immunogenic. ConclusionThe current study offered critical basic and conceptual information on ROP41 to increase a successful vaccine in opposition to continual and acute toxoplasmosis for in addition in vivo assessments. Further research is necessary for the development of vaccines utilizing ROP41 alone or combined with various antigens.

PREPARATION OF A SPECIFIC PEROXIDASE CONJUGATE TO THE CAUSATIVE AGENT OF CAMPYLOBACTERIOSIS

Immunoglobulins are protein compounds in blood plasma - glycoproteins, the main function of which is to protect the body from infections. Immune antibodies are divided into five classes - IgA, IgG, IgM, IgD, IgE. Great importance in diagnostic studies is attached to immunoglobulins IgG, IgA, IgM. During the study, their qualitative and quantitative content is determined. The first determines the presence of infection in the blood, the second determines the level of antibodies in the blood of the organism affected by the disease. For each infection there is a certain level of antibodies M and G in the blood, and some infections are not accompanied by an increase in the level of immunoglobulin. IgG antibodies are large molecules with a mass of about 150 kDa. These are specific antibodies produced by cells of the immune system in response to the attack of pathogens - causative agents of viral, bacterial, fungal and other diseases. G-class immunoglobulins (IgG) are dominant among all other serum immunoglobulins. They ensure the formation of long-term and stable, in some cases lifelong immunity against a number of serious pathologies such as measles, rubella, chickenpox. IgG makes up 80% of all immunoglobulins in the blood serum and up to 20% of its total proteins. Plasmocytes (mature B-lymphocytes) synthesize IgG. G-immunoglobulin (IgG). Immunoglobulins of this isotype have the classic monomeric form and provide the bulk of the antibodies synthesized during the second immune response. Because of its low molecular weight, IgG readily penetrates tissues and is the most studied immunoglobulin with the ability to penetrate the placental barrier. It passes through the placenta from mother to fetus and protects the baby from infection, many different viruses, providing the baby with humoral immunity until the first (until about 4-6 months of age) of its own immunity. Consequently, a newborn baby will have the same antibodies as its mother for the first five to six months of life, and thus will be able to protect itself from all the dangerous pathogens the baby encounters in the mother's life until these antibodies break down and disappear. This set of immunoglobulins is very important for the newborn, who is very susceptible to infections, especially in the respiratory and digestive systems that can activate the complement system. The main purpose of this work is to isolate and purify G-immunoglobulins from rabbit serum immunized with Campylobacteriosis pathogen antigen. As a result of precipitation and purification of rabbit blood serum immunized with Campylobacteriosis antigen-causing agent by saturated ammonium sulfate solution by chromatography method, G-immunoglobulin with a total volume of 30 ml and protein concentration of about 1 mg/ml was isolated. The obtained G-immunoglobulin will be used in the preparation of peroxidase conjugate specific for campylobacteriosis pathogen.

The impact of household size on measles transmission: A long-term perspective

Households play an important role in the transmission of infectious diseases due to the close contact therein. Previous modeling studies on disease transmission with household-level mixing have explored the relationship between household size distribution and epidemic characteristics such as final epidemic sizes and the basic reproduction number but have not considered the epidemic impact of declining household sizes caused by demographic shifts. Here, we use a disease transmission model that incorporates demographic changes in household sizes to study the long-term transmission dynamics of measles in communities with varying household size distributions. We explore the impact of incorporating both household- and age-structured mixing on the dynamic properties of the transmission model and compare these dynamics across different household size distributions. Our analysis, based on the household- and age-structured model, shows that communities with larger household sizes require higher vaccination thresholds and bear a greater burden of infections. However, simulations show the apparent impact of changing household sizes is the combined result of changing birth rates and household mixing, and that changing birth rates likely play a larger role than changes in household mixing in shaping measles transmission dynamics (n.b, life-long immunity makes replenishment of population susceptibility from births a crucial transmission driver for measles). In addition, simulations of endemic transmission of measles within a hypothetical population formulated using aggregated world demographic data suggest the decline in household size (driven by changing fertility rates of the population), in addition to increasing vaccination coverage, could have had a significant impact on the incidence of measles over time.

Unexpected high incidence of parvovirus B19 nucleic acid detection in German blood donors in the winter/spring season 2023/2024.

In healthy adults, parvovirus B19 (PVB19) typically causes mild symptoms but can lead to severe complications in immunosuppressed individuals or those with high red blood cell turnover. Infection can occur through respiratory transmission or via transfusion, necessitating the testing of blood donations in Germany. Between 2015 and April 2024, we screened 2 105 755 blood donations for PVB19 using polymerase chain reaction. Incidence rates were calculated for three periods: pre-COVID-19 (2015-2020), during the pandemic (2020-2023), and post-COVID-19 (2023-2024). A total of 242 PVB19-positive donations were identified. In the first period, there were 101 positives out of 1 228 361 donations (incidence: 0.83/10 000). In the second period, four positives were found out of 621 222 donations (incidence: 0.06/10 000). In the third period, 137 positives were detected out of 235 088 donations (incidence: 5.35/10 000) with a striking increase of incidence between December 2023 and March 2024 (4.3-21.1/10 000 donations). Most people develop lifelong immunity after infection in childhood but the COVID-19 pandemic interventions, like masks and distancing, correlate with a decline in PVB19 infections in donors indicating an impact of hygiene measures on PVB19 infection rates.

What's going on with measles?

Measles is a highly transmissible systemic viral infection associated with substantial mortality primarily due to secondary infections. Measles induces lifelong immunity to reinfection but loss of immunity to other pathogens. An attenuated live virus vaccine is highly effective, but lapses in delivery have resulted in increasing cases worldwide. Although the primary cause of failure to control measles is failure to vaccinate, waning vaccine-induced immunity and the possible emergence of more virulent virus strains may also contribute.

Congenital Rubella Syndrome Does Not Increase with Introduction of Rubella-Containing Vaccine.

Rubella infection is typically mild or asymptomatic except when infection occurs during pregnancy. Infection in early pregnancy can cause miscarriage, stillbirth, or congenital rubella syndrome. Only individuals that are still susceptible to rubella infection during child-bearing age are vulnerable to this burden. Rubella-containing vaccine (RCV) is safe and effective, providing life-long immunity. However, average age-at-infection increases with increasing vaccination coverage, which could potentially lead to increased disease burden if the absolute risk of infection during child-bearing age increases. The dynamics of rubella transmission were explored using EMOD, a software tool for building stochastic, agent-based infection models. Simulations of pre-vaccine, endemic transmission of rubella virus introduced RCV at varying levels of coverage to determine the expected future trajectories of disease burden. Introducing RCV reduces both rubella virus transmission and disease burden for a period of around 15 years. Increased disease burden is only possible more than a decade post-introduction, and only for contexts with persistently high transmission intensity. Low or declining rubella virus transmission intensity is associated with both greater burden without vaccination and greater burden reduction with vaccination. The risk of resurgent burden due to incomplete vaccination only exists for locations with persistently high infectivity, high connectivity, and high fertility. A trade-off between the risk of a small, future burden increase versus a large, immediate burden decrease strongly favors RCV introduction.

Leukolectins support lifelong innate immunity in lower vertebrates, and reveal dichotomies of several leukocytic lineages

Innate immunity is vital for animal homeostasis and survival. First-line immuno-defense for fish larvae involves mucus enriched with leukolectin (LL) secreted by dermal lectocytes. Later during the critical transition from yolk-nutrition to feeding, additional larval immuno-protection in zebrafish (zF) is provided by macrophages containing LL (lectophages). This work investigated new LL-expression in embryos and in blood, structures of fish leukocytic LL and LL-genes, and LL-presence in chicken leukocytes. In zF-embryos, lectophages appear ∼10 hpf, while later, cells co-expressing myeloperoxidase- and LL-mRNA were detected (∼19 hpf). Furthermore, protein-extracts of Atlantic salmon (Ssal) leukocytes contained LL-proteins, compartmentalized in the cytosol. Cloning and sequencing revealed 94 % nt-sequence identity between variants of Ssal-leukolectins. Highly conserved LLs allowed production of epitope-specific anti-LL IgGs. Immuno-fluorescence-analysis demonstrated that most Ssal-bloodcells were LL-negative, but both some large cells with protrusions and some small, rounded cells did express LL. Immunoperoxidase-staining method confirmed LL-expression in some Ssal-leukocytes, identified as macrophages, PMN-leukocytes, thrombocytes and dendritic cells. However, closer examination revealed a dichotomy of these cell-categories into either LL-positive, or LL-negative variants. In situ hybridization demonstrated profuse LL-expression in Ssal head kidney interstitial tissue, while LL-transcripts were absent in large kidney tubules. Both hematopoietic (non-pigmented) marrow cells and melano-macrophages expressed LL-mRNA, implying that leukolectins provide lifelong innate immuno-protection. PCR-amplification using Ssal-leukocytic DNA as template, and direct sequencing yielded a leukocytic ll-gene. Some cells in salmon, cod, halibut, oikopleura and zebrafish embryos express LL-proteins and/or LL-mRNA, and LL-mRNA is detected in salmon, cod and chicken leukocytes. However, current genomes for these species lack recognizable LL-loci except the Ssal_v3.1 Genome-assembly. The data demonstrate an unexpected dichotomy of some leukocyte lineages into LL-positive or LL-negative cell-variants. Such dichotomies suggest exploring differential impacts from the duplicated leukocyte-lineages in health and disease.

National Concept of Development of Vaccine Prophylaxis in Russia

The article is dedicated to outlining the conceptual directions for the development of vaccination in the Russian Federation. The provisions of the concept are formulated based on the authors' years of research on vaccination issues and analysis of data from domestic and foreign scientific literature. The main provisions of the concept aim at strengthening the state policy in the field of vaccination, reconstructing and expanding enterprises for the production of domestic vaccines, developing and improving immunobiological medicinal products against current infections, refining the National Immunization Schedule and Vaccination Schedule according to epidemiological indications; further promoting the WHO's "lifelong immunization" strategy; developing regional immunization programs; implementing a risk-oriented approach in the development of immunization programs; developing a system for monitoring post-vaccination complications; implementing epidemiological surveillance of vaccination as a methodology for assessing the strategy and tactics of immunization in accordance with the epidemiological situation; ensuring commitment to vaccination among the population, healthcare workers, and legislative and executive authorities.

Mechanistic insights into immune amnesia and immunity induced by measles infection and vaccination via comprehensive antiviral antibodies profiling

Abstract Measles is a disease known to induce acute immune amnesia and immunosuppression with increased susceptibility to other infections, while paradoxically conferring patients with life-long immunity to measles. However, it is not clear if the live-attenuated measles vaccine (LAMV) induces immunosuppression comparable to the wild-type measles (WT MeV) infection, nor how mechanistically LAMV and WT MeV affect antibodies specific to different pathogens. Therefore, we utilized VirScan, a phage-display immunoprecipitation and sequencing (PhIP-seq) technology for virome-wide detection of antibodies against viral epitopes, to compare longitudinal antibody diversity in plasma samples from WT MeV and LAMV-infected rhesus macaques (RMs) (n=10 and 6 respectively, with 5 longitudinal timepoints at D0, D14/15, D28, D84/89, D112/168/176). Preliminary analysis showed that WT MeV led to more long-term depletion of pre-existing antibodies to various viral peptides, while mounting a MeV-specific antibody response with greater intensity and breadth than LAMV-infected RM. Furthermore, in our sex difference analysis, male RMs elicited a stronger MeV response than female, particularly to N protein; also a more polyclonal MeV humoral response In summary, our work provided crucial mechanistic insights into immune amnesia and immunity induced by natural infection versus vaccination, highlighting the public health value of the measles vaccine in averting MeV-induced immune amnesia.

Bayesian modeling of post-vaccination serological data suggests that yearly vaccination of dog aged

Rabies control remains challenging in low and middle-income countries, mostly due to lack of financial resources, rapid turnover of dog populations and poor accessibility to dogs. Rabies is endemic in Cambodia, where no national rabies vaccination program is implemented. The objective of this study was to assess the short and long-term vaccination-induced immunity in Cambodian dogs under field conditions, and to propose optimized vaccination strategies. A cohort of 351 dogs was followed at regular time points following primary vaccination only (PV) or PV plus single booster (BV). Fluorescent antibody virus neutralization test (FAVNT) was implemented to determine the neutralizing antibody titer against rabies and an individual titer ≥0·5 IU/mL indicated protection. Bayesian modeling was used to evaluate the individual duration of protection against rabies and the efficacy of two different vaccination strategies. Overall, 61% of dogs had a protective immunity one year after PV. In dogs receiving a BV, this protective immunity remained for up to one year after the BV in 95% of dogs. According to the best Bayesian model, a PV conferred a protective immunity in 82% of dogs (95% CI: 75-91%) for a mean duration of 4.7 years, and BV induced a lifelong protective immunity. Annual PV of dogs less than one year old and systematic BV solely of dogs vaccinated the year before would allow to achieve the 70% World Health Organization recommended threshold to control rabies circulation in a dog population in three to five years of implementation depending on dog population dynamics. This vaccination strategy would save up to about a third of vaccine doses, reducing cost and time efforts of mass dog vaccination campaigns. These results can contribute to optimize rabies control measures in Cambodia moving towards the global goal of ending human death from dog-mediated rabies by 2030.

Expanded spectrum of varicella disease and the need for vaccination in India.

Varicella vaccine was first licensed in Japan and South Korea in 1989 for use in healthy children and was introduced in US in 1995. So far, 29 countries have adopted varicella vaccine in their universal immunization program (UIP). No Asian country, India included, has adopted the varicella vaccine as part of their UIP. The extra-cutaneous sites for VZV diseases are central nervous system and gastrointestinal tract, the expanded disease spectrum includes vasculopathy, myelitis, inflammatory bowel disease, perforated ulcers, and gastritis. The actual disease burden of varicella is not known as most of the infected individuals may not visit the physician. The amplifiable VZV DNA will not always be detectable in cerebrospinal fluid (CSF) samples in protracted illnesses such as vasculopathies, but demonstrable anti-VZV IgG in CSF has diagnostic value. The World Health Organization (WHO) position paper 2014 recommends two doses of varicella and zoster vaccines in targeted population. In India, varicella vaccine is not included in the UIP due to the cost and the belief that lifelong immunity occurs following primary infection. The expanded spectrum of VZV disease and the mounting body of evidence, however, suggest the need for both varicella and zoster vaccines in routine immunization schedule.

A study on the factors influencing the intention to receive booster shots of the COVID-19 vaccine in China based on the information frame effect.

In the response to and prevention and control of the Novel coronavirus pneumonia, the COVID-19 vaccine does not provide lifelong immunity, and it is therefore important to increase the rate of booster shots of the COVID-19 vaccine. In the field of information health science, research has found that information frames have an impact in changing individual attitudes and health behaviors. This study focuses on the effects of different influencing factors on the public's willingness to receive the booster shots of the COVID-19 vaccine under two information frameworks. An online questionnaire was conducted to explore the effects of demographic characteristics, personal awareness, social relationships, risk disclosure, perceived booster vaccination protection rate, and duration of protection under the assumption of an information framework. T test and one-way analysis were used to testing the effect of variables. (1) The persuasion effect under the gain frame is higher than that under the loss frame (B = 0.863 vs. B = 0.746); (2) There was no significant difference in subjects' intention of booster vaccination in terms of gender, age, income, occupation, educational background and place of residence. Whether family members received booster vaccination was strongly correlated with their intention of vaccination under the loss framework (p = 0.017, M = 4.63, SD = 0.664). (3) The higher the understanding of COVID-19, the higher the degree of compliance with the government's COVID-19 prevention and control measures, and the higher the willingness to strengthen vaccination; (4) Risk disclosure has a significant impact on people's willingness to receive COVID-19 booster shots (M = 2.48, under the loss framework; M = 2.44, under the gain framework); (5) Vaccine protection rate and duration of protection have an impact on people's willingness to vaccinate. Increased willingness to vaccinate when the protection rate of booster vaccine approaches 90% (M = 4.76, under the loss framework; M = 4.68, under the gain framework). When the vaccine protection period is 2 years, people are more willing to receive a booster vaccine; and the willingness to receive a booster shot is stronger under the loss framework (M = 4.60, SD = 0.721, p = 0.879). The impact of the information framework on COVID-19 vaccination intentions is different, and the disclosure of relevant health information should focus on the impact of the information framework and content on the public's behavior toward strengthening vaccination. Therefore, in the face of public health emergencies, public health departments, healthcare institutions, and other sectors can consider adopting the Gainful Information Framework tool to disseminate health information to achieve better persuasion and promote public health behavior change enhancing public health awareness, and promoting universal vaccination.

The life-long protective immunity of yellow fever vaccination: time to review?

The life-long protective immunity of yellow fever vaccination: time to review?

Effects of boosting and waning in highly exposed populations on dengue epidemic dynamics.

Sequential infection with multiple dengue virus (DENV) serotypes is thought to induce enduring protection against dengue disease. However, long-term antibody waning has been observed after repeated DENV infection. Here, we provide evidence that highly immune Nicaraguan children and adults (n = 4478) experience boosting and waning of antibodies during and after major Zika and dengue epidemics. We develop a susceptible-infected-recovered-susceptible (SIRS-type) model that tracks immunity by titer rather than number of infections to show that boosts in highly immune individuals can contribute to herd immunity, delaying their susceptibility to transmissible infection. In contrast, our model of lifelong immunity in highly immune individuals, as previously assumed, results in complete disease eradication after introduction. Periodic epidemics under this scenario can only be sustained with a constant influx of infected individuals into the population or a high basic reproductive number. We also find that Zika virus infection can boost DENV immunity and produce delays and then surges in dengue epidemics, as observed with real epidemiological data. This work provides insight into factors shaping periodicity in dengue incidence and may inform vaccine efforts to maintain population immunity.

Computer-aided Affinity Enhancement of a Cross-reactive Antibody against Dengue Virus Envelope Domain III.

The dengue virus (DENV), composed of four distinct but serologically related Flaviviruses, causes the most important emerging viral disease, with nearly 400 million infections yearly. Currently, there are no approved therapies. Although DENV infection induces lifelong immunity against the same serotype, the antibodies raised contribute to severe disease in heterotypic infections. Therefore, understanding the mechanism of DENV neutralization by antibodies is crucial in the design of vaccines against all serotypes. This study reports a comparative structural and energetic analysis of the monoclonal antibody (mAb) 4E11 in complex with its target domain III of the envelope protein for all four DENV serotypes. We use extensive replica molecular dynamics simulations in conjunction with the binding free energy calculations. Further single point and double mutations were designed through computational site-directed mutagenesis and observed that the re-engineered antibody exhibits high affinity to binding and broadly neutralizing activity against serotypes. Our results showed improved binding affinity by the gain of enthalpy, which could be attributed to the stabilization of salt-bridge and hydrogen bond interactions at the antigen-antibody interface. The findings provide valuable results in understanding the structural dynamics and energetic contributions that will be helpful to the design of high-affinity antibodies against dengue infections.

Mpox in people with past infection or a complete vaccination course: a global case series

Since May, 2022, a large global outbreak of human mpox (formerly known as monkeypox) has predominantly affected men who have sex with men. The strain responsible, Clade IIb, has mutated substantially from precursors originating from the 2017-18 outbreak in Nigeria. Immunity to smallpox, another orthopoxvirus, via previous infection or vaccination provides lifelong immunity. However, since the 2022 mpox outbreak, recent clusters were described in individuals with presumed immunity through recent infection or vaccination. We aim to describe the epidemiological and clinical characteristics of mpox in individuals with past infection or vaccination to improve the understanding of this disease in the setting of previous immunity. In this global case series, international collaborators from nine countries provided data on individuals with PCR-confirmed mpox after documented previous infection or vaccination between May 11, 2022, and June 30, 2023. We excluded cases that could not confirm vaccination status or cases with partial immunisation or any doses received before the current multi-national mpox outbreak (cutoff date May 1, 2022). Data were collected via a case report spreadsheet that reported on dates of infection and vaccination, route of immunisation, demographic characteristics, clinical findings, HIV status, concomitant sexually transmitted infections, and markers of disease severity (mpox severity score system). We describe case epidemiology, clinical course, and mpox severity scores; all analyses were descriptive. We report mpox infections in 37 gay and bisexual men who have sex with men: seven individuals had mpox reinfections, 29 individuals had mpox infections that occurred after two appropriately spaced Modified Vaccinia Ankara-Bavarian Nordic vaccine courses, and one individual had an infection that met the criteria for both reinfection and infection after vaccination. The median age of individuals was 36 years (IQR 30-45; range 21-58). Those with natural immunity after initial infection had a shorter disease course with less mucosal disease upon reinfection than with their initial infection. Infections post-vaccination were characterised by few lesions, little mucosal disease, and minimal analgesia requirements; two people received oral tecovirimat. Overall, there were no deaths, no bacterial superinfections, and all individuals were managed in the ambulatory clinic with one hospital admission for a necrotising neck lesion. The epidemiology of people with mpox reinfection or infection post-vaccination was similar to other published cohorts during the 2022 outbreak-predominantly young, sexually active gay and bisexual men who have sex with men. Clinical features and outcomes of repeat infection and infection after vaccination appear to be less clinically severe than those described in 2022 case literature. Specifically, compared with the 2022 case series, these individuals in the present study had fewer confluent lesions, less mucosal involvement, reduced analgesia requirement, and fewer admissions. Natural immunity and vaccine-induced immunity are not fully protective against mpox infection. However, in this small series both disease duration and severity appear to be reduced. None.

A Cross-sectional Survey of Public Knowledge and Perspective on Coronavirus Disease, Vaccination, and Related Research in India during the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has left no person unexposed to the wisdom about the need for human preparedness to tackle future pandemics irrespective of individual caste, race, religion, and education status. The extent of this change in knowledge and public perspective is difficult to measure in a populous nation like India subjected to individual freedom and cultural beliefs. Hence, we planned this study with the objective of evaluating the knowledge and perception of the Indian public towards COVID-19 disease, vaccination and research activities associated with the COVID-19 pandemic. This is an observational, single-center, cross-sectional study (n = 244) conducted after obtaining approval from the Ethics Committee for Academic Research Projects. All consenting study participants, Indian residents aged > 18 years, were administered a prevalidated and structured questionnaire and interviewed for their honest opinion. The outcome measures were to evaluate the knowledge and perception of the study participants in each of the domains of COVID-19 disease, COVID-19 vaccination, and COVID-19-related clinical research. Demographic characteristics were summarized using descriptive statistics. All analyses were done at a 5% significance level using GraphPad InStat version 3.1. Data on the proportion of participants' responses to the questions in each of the three domains of COVID-19 disease (D), COVID-19 vaccination (V), and COVID-19-related research (R) were assessed. Study participants who knew the causative agent for coronavirus disease were 93.03% (227/244), nomenclature (77.45%, 189/244), those who could define pandemic (89.34%, 218/244), preventive measures against covid (96.31%, 235/244), lungs as the most common organ affected (96.31%, 235/244) and all answered that the origin of novel coronavirus was China. The majority of them felt that COVID-19 pandemic waves would never end (39.34%, 96/244), there was no effective drug/vaccine therapy available, and the lack of oxygen/hospital beds (39%) resulted in maximum mortality, and 47.13% (115/244) were worried about future bioterrorism. The lockdown measures were justified by 161/244 (65.98%), and 93.85% supported lockdown measures to curb the spread of infection. The improvement in air quality/environment hygiene, realizing the importance of hygiene, vaccine and disease, and spending quality time with family were the best three things to happen during the pandemic, while the loss of wages, nonavailability of medicines/vaccines/oxygen/hospital beds with mental/physical health deterioration were the worst three things experienced by people. Regarding COVID-19 vaccination, the most common reason to get vaccinated was to prevent infection/critical outcomes of COVID-19 (78.27%, 191/244); 79% already suffered COVID-19 prior to vaccination, while 68.85% suffered a COVID-19 infection after taking the vaccine which was mostly asymptomatic/mild. Almost 56.96% (139/244) participants supported compulsory vaccination for all in the larger interest of society and to prevent fatal COVID-19 outcomes. There were safety concerns mainly with accelerated approval of vaccines (4.1%, 10/244) among the public, and 32.78% (80/244) attributed limited infrastructure/vaccination centers/healthcare staff as the major challenge of a mass vaccination program with 71.72% (175/244) supporting the vehicle/home vaccination drives to meet the vaccination demand in the pandemic. Approximately 38.11% (93/244) blamed the lack of sufficient vaccine manufacturing sites in India as a major vaccine shortage. Almost 82% public knew that vaccines are incapable of providing lifelong immunity or conferring protection against multiple variants, with 34.83% desiring to get polyvalent vaccines that would provide immunity against multiple COVID-19 variants. A total of 57.37% knew about clinical research, believed that the vaccine/drug development process was slow in India (29.91%), that there was a lack of funds invested in COVID-19-related clinical research (62.29%), 47.95% felt no attention was given to the alternative system of medicines, 77.86% supported accelerated drug/vaccine approval in the pandemic. Around 64.34% of the study, participants knew about the available and approved COVID-19 treatment options, such as antiviral drugs, monoclonal antibodies and vaccines. Of the total 244 study participants, 98.36% believed that clinical research is important for science to progress. When asked about their willingness to participate in COVID-19 clinical research, only 40.57% agreed, while 29% opted for non-COVID-19 related clinical research, and 29% refused to participate in any kind of clinical research. Almost 88.93% refused to take medicines without approval by drug regulatory bodies, and 54.51% agreed to participate in a controlled human challenge research study during the pandemic. The majority were of the opinion that lack of financial support (35.24%) was the main hindrance to the conduct of clinical research in India and the reason for lagging behind other countries in research and development (64.34%). The survey provides insight into the public awareness and perception of the pandemic that has taught all the lessons for capacity building in automation, construction of robust medical infrastructure, and the need for future preparedness. How to cite this article: Munshi R, Maurya M. A Cross-sectional Survey of Public Knowledge and Perspective on Coronavirus Disease, Vaccination, and Related Research in India during the COVID-19 Pandemic. J Assoc Physicians India 2023;71(9):19-27.

Defining the identity and the niches of epithelial stem cells with highly pleiotropic multilineage potency in the human thymus

Thymus is necessary for lifelong immunological tolerance and immunity. It displays a distinctive epithelial complexity and undergoes age-dependent atrophy. Nonetheless, it also retains regenerative capacity, which, if harnessed appropriately, might permit rejuvenation of adaptive immunity. By characterizing cortical and medullary compartments in the human thymus at single-cell resolution, in this study we have defined specific epithelial populations, including those that share properties with bona fide stem cells (SCs) of lifelong regenerating epidermis. Thymic epithelial SCs display a distinctive transcriptional profile and phenotypic traits, including pleiotropic multilineage potency, to give rise to several cell types that were not previously considered to have shared origin. Using here identified SC markers, we have defined their cortical and medullary niches and shown that, invitro, the cells display long-term clonal expansion and self-organizing capacity. These data substantively broaden our knowledge of SC biology and set a stage for tackling thymic atrophy and related disorders.

Natural products to reduce the severity of coronavirus 2019: A literature review

The COVID-19 pandemic may affect a large number of people. The coronavirus could re-infect someone in 2019. Nevertheless, work on developing new vaccines for lifelong immunization continues. Herbs for the intervention of life-threatening virus may be an alternative for people in order to lessen the severity of disease in susceptible patients. The objective of this paper is to present active components that have a strong potential to inhibit viral replication and reduce inflammation in patients with pneumonia. Numerous substances, including andrographolide (Andrographis), quercetin (Finger root), and curcumin (Turmeric), have biological activities. They were considered to be top-tier natural items. Thailand may be mandated to conduct research and ongoing development in the field of clinical testing on Thai and Chinese herbs, particularly artemisinin, in order to achieve this. As a result, these results will help with coronavirus infection therapy and symptom reduction in patients.

Dynamics of Humoral Immunity to Myxoma and Rabbit Hemorrhagic Disease Viruses in Wild European Rabbits Assessed by Longitudinal Semiquantitative Serology.

Myxoma virus (MYXV) and rabbit hemorrhagic disease virus (RHDV) are important drivers of the population decline of the European rabbit, an endangered keystone species. Both viruses elicit strong immune responses, but the long-term dynamics of humoral immunity are imperfectly known. This study aimed to assess the determinants of the long-term dynamics of antibodies to each virus based on a longitudinal capture-mark-recapture of wild European rabbits and semiquantitative serological data of MYXV and RHDV GI.2-specific IgG. The study included 611 indirect enzyme-linked immunosorbent assay (iELISA) normalized absorbance ratios for each MYXV and RHDV GI.2 from 505 rabbits from 2018 to 2022. Normalized absorbance ratios were analyzed using log-linear mixed models, showing a significant positive relationship with the time since the first capture of individual rabbits, with monthly increases of 4.1% for antibodies against MYXV and 2.0% against RHDV GI.2. Individual serological histories showed fluctuations over time, suggesting that reinfections boosted the immune response and likely resulted in lifelong immunity. Normalized absorbance ratios significantly increased with the seroprevalence in the population, probably because of recent outbreaks, and with body weight, highlighting the role of MYXV and RHDV GI.2 in determining survival to adulthood. Juvenile rabbits seropositive for both viruses were found, and the dynamics of RHDV GI.2 normalized absorbance ratios suggest the presence of maternal immunity up to 2 months of age. Semiquantitative longitudinal serological data provide epidemiological information, otherwise lost when considering only qualitative data, and support a lifelong acquired humoral immunity to RHDV GI.2 and MYXV upon natural infection. IMPORTANCE This study addresses the long-term dynamics of humoral immunity to two major viral pathogens of the European rabbit, an endangered keystone species of major ecological relevance. Such studies are particularly challenging in free-ranging species, and a combination of longitudinal capture-mark-recapture and semiquantitative serology was used to address this question. Over 600 normalized absorbance ratios of iELISA, obtained from 505 individual rabbits in 7 populations over 5 years, were analyzed using linear mixed models. The results support a lifelong acquired humoral immunity to myxoma virus and rabbit hemorrhagic disease virus upon natural infection and suggest the presence of maternal immunity to the latter in wild juvenile rabbits. These results contribute to understanding the epidemiology of two viral diseases threatening this keystone species and assist in developing conservation programs.