Effective Vaccine Research Articles

Effects of vaccination on antibody level and duration of viral shedding in Omicron patients.

We compared the clinical characteristics of vaccinated and non-vaccinated Omicron patients in order to provide a reference for the clinical diagnosis and treatment of coronavirus disease 2019 (COVID-19). This study included 360 patients diagnosed with COVID-19. The serum immunoglobulin G (IgG) and serum immunoglobulin M (IgM) antibody levels of the patients and the duration of virus shedding were analyzed according to age, gender, vaccine dose, and the time from the most recent vaccination to the onset of Omicron infection. Age (OR = 0.974), days from last vaccination to onset ≤ 180 days (OR = 4.409), and booster dose of the vaccine (OR = 4.999) were protective factors associated with patients who were IgG antibody positive. The duration of virus shedding in IgG -antibody-positive patients was 9 (8-11) days; and this was significantly lower than that in IgG-antibody-negative patients, who had virus shedding duration of 10 (8-12) days (p < 0.05). Booster immunizations could increase IgG-antibody in patients who have already been infected with the Omicron variant and enhance immune protection. In addition, COVID-19 vaccination may shorten the duration of virus shedding.

Seroprevalence of Bordetella pertussis infection in children 1-14 years old: Indonesia basic health research (Riskesdas) 2013 and 2018 data.

Bordetella pertussis infection is a highly contagious respiratory disease that can cause complications such as pneumonia and death. A total of 62,646 cases of pertussis worldwide were reported by WHO in 2022. This study aimed to obtain the pertussis seroprevalence and sociodemographic data in children aged 1-14 years and its association factors in the community based on Riskesdas 2013 and 2018. Bivariate and multivariate analysis was carried out on data from 12,753 children aged 1-14 years collected from Riskesdas 2013 and 2018 in Indonesia. Pertussis serology data was obtained based on the results of the ELISA examination which was categorized as seropositive if anti-pertussis toxin IgG ≥ 100 IU/mL or anti-pertussis IgG > 11 NTU. Pertussis seropositive indicated recent pertussis infection if no pertussis vaccine was received within the last twelve months. Pertussis seroprevalence was found at 9.8% and 33.4% in Riskesdas 2013 and 2018 respectively. While 10.1% of children aged 5-14 years were found pertussis seropositive by excluding the possible effect of vaccination in the last twelve months in Riskesdas 2013. The most important associated factor in seropositive pertussis at ages 1-4 years and 5-14 years was a history of pneumonia in the last month (OR = 2.709, 95%CI: 2.592-2.831 in Riskesdas 2013 and OR = 2.421, 95%CI: 2.299-2.550 in Riskesdas 2018). In the adjusted analysis for respondents' characteristics, low maternal education was the predictive factor that most influenced pertussis seropositivity, especially in the 2013 Riskesdas (APOR = 2.983, 95%CI: 2.670-3.333). In conclusion, the results of this study showed that the seroprevalence of pertussis was high, especially in children aged 5-14 years, so that pertussis vaccine booster administration could be considered. Because the most influencing factor towards pertussis seropositive was low maternal education, the groups of children with low-educated mothers should be targets for strengthening complete vaccination coverage and disease control.

COVID-19 and Service Provisions at Darou Khoudous Health Center of Touba

Introduction: The objective is to study the consequences of COVID-19 on service provision at the Serigne Mbacke Madina health center in Darou Khoudous in the Touba district. Materials and methods: To achieve this objective, a retrospective, descriptive study was conducted from July 2021 to December 2021. Results: Over the period 2016-2020, the age group 50-59 years and 60 years and over rarely attended the health structure. This low attendance at the health structure was further accentuated in 2020. According to consultation by service: We note that General Medicine, TRI and On-call are quite busy over the period with a significant drop in these consultations within these services in 2020. Indeed, General Medicine went from 37,378 patients in 2017 to 22,332 patients in 2020, i.e. 40%, TRI went from 35,461 patients in 2017 to 26,080 patients in 2020, i.e. 26.45%, and On-call went from 21,880 patients to 12,008 patients in 2020, i.e. 45.11%. Between 2019 and 2020 in Medicine we noted a decrease of 27.84%, in TRI a decrease of 27.8%. For patients followed for HIV at the Darou Khoudous health center, we noticed an almost complete absence of the 0-14 age group. We also noticed a low rate of new cases before 2018 and a sharp drop in the rate of new cases in 2020, a decrease of 87.84% compared to 2019. For tuberculosis patients followed in the department, we noted a strong impact on the age group &amp;gt;15 years, more accentuated between 15 and 35 years over the period 2016-2020. For this same age group, we also noticed a decrease in cases between 2019 and 2020, a decrease of 10%. In 2018 we also noticed a peak in cases compared to the previous 2 years. According to the EPI: variations are almost non-existent during the pandemic, on the contrary, attendances have increased since 2016, this would surely be due to awareness of the beneficial effects of EPI vaccines and that the disease initially only affected the elderly, rare are the cases of children reported. Conclusion: The data collected as part of this study show that the COVID-19 pandemic has disrupted health services and put intolerable pressure on health systems and their staff. We urgently need to reverse this trend and strengthen the resilience of health systems.

Targeted recruitment of immune effector cells for rapid eradication of influenza virus infections

Despite much research, considerable data suggest that influenza virus remains a serious health problem because i) the effectiveness of current vaccines ranges only from 19% to 60%, ii) available therapies remain ineffective in advanced stages of disease, iii) death rates vary between 25,000 and 72,000/year in the United States, and iv) avian influenza strains are now being transmitted to dairy cattle that in turn are infecting humans. To address these concerns, we have developed zanDR, a bispecific small molecule that binds and inhibits viral neuraminidase expressed on both free virus and virus-infected cells and recruits naturally occurring anti-rhamnose and anti-dinitrophenyl (DNP) antibodies with rhamnose and DNP haptens. Because the neuraminidase inhibition replicates the chemotherapeutic mechanism of zanamivir and oseltamivir, while rhamnose and DNP recruit endogenous antibodies much like an anti-influenza vaccine, zanDR reproduces most of the functions of current methods of protection against influenza virus infections. Importantly, studies on cells in culture demonstrate that both of the above protective mechanisms remain highly functional in the zanDR conjugate, while studies in lethally infected mice with advanced-stage disease establish that a single intranasal dose of zanDR not only yields 100% protection but also reduces lung viral loads faster and ~1,000× more thoroughly than current antiviral therapies. Since zanDR also lowers secretion of proinflammatory cytokines and protects against virus-induced damage to the lungs better than current therapies, we suggest that combining an immunotherapy with a chemotherapy in single pharmacological agent constitutes a promising approach for treating the more challenging forms of influenza.

Isolation and characterization of &lt;i&gt;Salmonella enterica &lt;/i&gt; associated with diarrhea in chickens and ducks in Hai Duong province

Salmonella infections, or salmonellosis, represent a significant threat to poultry health and the global poultry industry, leading to considerable economic losses and serving as a major source of foodborne illnesses in humans and animals. Identifying the specific strains present in local poultry farms is crucial for implementing targeted interventions, including the development of effective biosecurity measures, vaccination strategies, and treatment protocols to mitigate outbreaks. This study focuses on isolating and characterizing Salmonella strains associated with diarrhea in chickens and ducks in Hai Duong province, Vietnam. The Salmonella strains were initially isolated using a culture-based method, followed by identification and characterization through Matrix-Assisted Laser Desorption Ionization/Time of Flight (MALDI-TOF), PCR amplification of the invA gene, and 16S rRNA gene sequencing. As a result, 18 Salmonella isolates were obtained, all of which contained the invA gene, indicating its potential significance in Salmonella pathogenesis. Analysis of the 16S rRNA gene sequences confirmed that all isolates belonged to the species Salmonella enterica, a well-known causative agent of intestinal diseases in humans and animals. Furthermore, phylogenetic analysis revealed that all 18 isolates grouped with Salmonella enterica subsp. enterica strains from China and Korea, suggesting a close relationship with strains circulating in the broader Southeast Asian region. This regional similarity may be attributed to the movement of poultry and poultry products, facilitating the cross-border spread of Salmonella. Our findings underscore the importance of implementing robust biosafety measures throughout the poultry production chain to control the spread of Salmonella, thereby enhancing both animal and food safety.

Structural Prediction and Antigenic Analysis of ROP18, MIC4, and SAG1 Proteins to Improve Vaccine Design against Toxoplasma gondii: An In silico Approach.

Toxoplasmosis is a cosmopolitan infectious disease in warm-blooded mammals that poses a serious worldwide threat due to the lack of effective medications and vaccines. The purpose of this study was to design a multi-epitope vaccine using several bioinfor-matics approaches against the antigens of Toxoplasma gondii (T. gondii). Three proteins of T. gondii, including ROP18, MIC4, and SAG1, were analyzed to predict the most dominant B- and T-cell epitopes. Finally, we designed a chimeric immunogen RMS (ROP18, MIC4, and SAG1) using some domains of ROP18 (N377-E546), MIC4 (D302-G471), and SAG1 (T130-L299) linked by rigid linker A (EAAAK) A. Physicochemical prop-erties, secondary and tertiary structures, antigenicity, and allergenicity of RMS were predicted utilizing immunoinformatic tools and servers. RMS protein had 545 amino acids with a molecular weight (MW) of 58,833.46 Da and a theoretical isoelectric point (IP) of 6.47. The secondary structure of RMS protein con-tained 21.28% alpha-helix, 24.59% extended strand, and 54.13% random coil. In addition, eval-uation of antigenicity and allergenicity showed the protein to be an immunogen and non-aller-gen. The results of the Ramachandran plot indicated that 76.4%, 12.9%, and 10.7% of amino acid residues were incorporated in the favored, allowed, and outlier regions, respectively. ΔG of the best-predicted mRNA secondary structure was -593.80 kcal/mol, which indicated that a stable loop was not formed at the 5' end. Finally, the accuracy and precision of the in silico analysis must be confirmed by successful heterologous expression and experimental studies.

Measles in the elimination period: the epidemic situation in Voronezh region

Vaccine-preventable diseases, one of which is measles, do not lose their importance and still remain a threat to public health. There is a deterioration in the epidemic situation regarding measles, both in the world and in the Russian Federation. The purpose of the study was to characterize the manifestations of the measles epidemic process in the Voronezh region for the period 1940–2023. The study of morbidity was carried out on the basis of data from Rosstat Form 2, 146 maps of the epidemiological investigation of a case of measles in the Voronezh region for the period 2011–2023 with the calculation of basic statistical indicators. The general availability of effective measles vaccination led to a decrease in the incidence, which by the beginning of the 21st century had become sporadic. However, from 2011 to 2023, there is an upward trend in incidence: rates increased from 0.27 cases (95 % CI 0.06–0.48) to 2.14 per 100 thousand population (95 % CI: 1.54–2,74); the risk group were children (average age 5.70 ± 0.24 years). From 2011 to 2015 imported cases predominated; since 2016 local cases predominated. For 2011–2023 146 cases (81 outbreaks) of measles were registered; among those who fell ill, the majority were not vaccinated against this infection or did not know about their vaccination status. Seroprotection level for the period 2011–2023 averaged 94.09±0.41 %; in certain years, there was an insufficient level of the immune layer in indicator groups of the population 16–17 years old and older. Thus, the pronounced activation of the measles epidemic process in the Voronezh region in recent years is due to a decrease in the immune layer.

Tetracistronic minigenomes elucidate a functional promoter for Ghana virus and unveils Cedar virus replicase promiscuity for all henipaviruses.

Henipaviruses are recognized as significant global health threats due to their high mortality rates and lack of effective vaccines or therapeutics. Due to the requirement for high biocontainment facilities, the scope of research which may be conducted on henipaviruses is limited. To address this challenge, we developed innovative tetracistronic, transcription, and replication-competent minigenomes. We demonstrate that these systems replicate key aspects of the viral life cycle, such as budding, fusion, and receptor binding, and are safe for use in lower biocontainment settings. Importantly, the application of this system to the Ghana virus revealed that its known sequence is incomplete; however, substituting the missing sequences with those from other henipaviruses allowed us to overcome this challenge. We demonstrate that the Ghana virus replicative machinery is functional and can identify two orally efficacious antivirals effective against it. Our research offers a versatile system for life-cycle modeling of highly pathogenic henipaviruses at low biocontainment.

Genetic polymorphism of Duffy binding protein in Pakistan Plasmodium vivax isolates

Plasmodium vivax Duffy binding protein (PvDBP) is crucial for erythrocyte invasion, interacting with the Duffy Antigen Receptor for Chemokines (DARC) on the erythrocyte surface. The amino-terminal cysteine-rich region II of PvDBP (PvDBPII) is a promising blood stage vaccine candidate, yet the genetic polymorphisms of this protein in global P. vivax isolates complicate the design of effective vaccines against vivax malaria. This study analyzed the genetic polymorphism of PvDBPII in Pakistan P. vivax isolates. A total of 29 single nucleotide polymorphisms (SNPs), including 22 nonsynonymous SNPs, were identified in 118 Pakistan PvDBPII. Most amino acid substitutions occurred in subdomains II and III, with six commonly observed in the global PvDBPII population. The amino acid change patterns in Pakistan PvDBPII generally mirrored those in global PvDBPII, although the frequencies of amino acid changes varied by country. Nucleotide diversity in Pakistan PvDBPII was comparable to that found in global PvDBPII. Evidence of natural selection and recombination in Pakistan PvDBPII aligned with observations in global PvDBPII. Analysis of the haplotype network of global PvDBPII revealed a complexed network of 167 haplotypes, but no geographical clustering was observed. The findings are crucial for understanding the genetic characteristics of Pakistan PvDBPII. A comprehensive analysis of nucleotide diversity and evolutionary trends in the global PvDBPII population offers valuable insights for the development of vivax malaria vaccines based on this antigen.

Computational Workflow to Design Novel Vaccine Candidates and Small-Molecule Therapeutics for Schistosomiasis.

Human schistosomiasis, caused by the Schistosoma trematode, is a neglected parasitic disease affecting over 250 million people worldwide. There is no vaccine, and the single available drug is threatened by drug resistance. This study presents a computational approach to designing multiepitope vaccines (MEVs) targeting the cercarial (CMEV) and schistosomular (SMEV) stages of schistosomes, and identifies potential schistosomicidal compounds from the Medicine for Malaria Ventures (MMV) and SuperNatural Database (SND) libraries. The designed vaccines (CMEV and SMEV) are engineered to provoke robust immune responses by incorporating a blend of T- and B-cell epitopes. Structural and immunoinformatics evaluations predicted robust interactions of CMEV and SMEV with key immune receptors and prolonged immune responses. In addition, molecular docking identified several compounds from the MMV and SND libraries with strong binding affinities to vital Schistosoma cathepsin proteases, indicating their potential as schistosomicidal agents. Our findings contribute to the potential development of effective vaccines and drugs against schistosomiasis.

Assessment of “Knowledge, attitudes and practice” of the population of the Republic of Tajikistan regarding COVID-19

Introduction. Despite the high level of vaccination, some groups of the population still lack reliable information about vaccines and resources with which to familiarize themselves with it. Social and behavioral changes are a key element of an effective response to COVID-19, such as increasing the level of knowledge of the population through the dissemination of information and educational materials on vaccination of the population against coronavirus infection. The purpose of the study: to assess the level of knowledge about COVID-19, behavioral practices, as well as attitudes towards vaccination and other ongoing anti-epidemic measures among the population of the Republic of Tajikistan. Materials and methods. The study was conducted by the NGO “Subhi Tandurusti” from February to May 2024. To assess the level of respondents in the Knowledge, Attitudes and Practices survey regarding issues related to COVID-19, a questionnaire survey was conducted using a specially designed questionnaire. The study involved 2,500 respondents from 15 different districts and cities of the republic. Results. About 93 % of respondents (n = 2322) correctly answered this question regarding modes of transmission of the virus, indicating a high level of awareness of modes of transmission of COVID-19. Relatively high rates of correct answers were recorded to the question “Is it possible to get sick with COVID-19 several times?” 69.5 % of respondents (n = 1737) answered this question correctly, indicating an understanding that it is possible to get sick with COVID-19 several times. Attitude of respondents regarding the safety and effectiveness of vaccination: 78.3 % of respondents (n = 1957) expressed confidence in its safety, 11.3 % (n = 282) did not know the answer, and 10.4 % (n = 261) did not consider the vaccine safe. 2,430 people (97.20 %) have already received the full course of vaccination against COVID-19, 42 people (1.68 %) have only received the first dose of the vaccine and are planning to receive the second. The most popular source of information about COVID-19 was television programs – 44.0 % of respondents (n = 1101), followed by information materials (25.2 %, n = 631) and the Internet, including websites and social networks (22.8 %, n = 571). At the same time, 75.6 % (n = 1889) of respondents rated information and educational materials about COVID-19 as very useful and reliable. To the question “Have you been tested?”: 639 people (25.6 %) “never” got tested, 588 (23.5 %) “often” and 461 (18.4 %) “always” got tested. Conclusion. The results of the study showed that the interviewees had sufficient knowledge about COVID-19, including the transmission of the virus through various routes and clinical symptoms of the disease, as well as the importance of vaccination. Public health initiatives help better protect public health during emergencies such as infectious disease pandemics.

Lung damage in SARS-CoV-2 patients: An autopsy study in the era of vaccination.

The contribution of SARS-CoV-2 infection on lung damage and the effect of vaccination on either containing the number of deaths or mitigating lung damage has not been systematically investigated. Post-mortem analysis was performed among consecutive in-patients with COVID-19 deceased in the Province of Trieste (2020-2022). The outcomes of the study were (i) rates of in-hospital mortality, (ii) contribution of COVID-19 to death, (iii) histological extent of lung injury and (iv) impact of vaccination. A total of 1038 consecutive hospitalized patients who died with SARS-CoV-2 infection were autopsied and deep histological analysis of the lungs was performed in a randomly selected sample of 508 cases. Among them, SARS-CoV-2 infection was (a) the cause of death (n = 90), (b) contributing to death (n = 304) and (c) an accompanying feature (n = 114). The incidence of SARS-CoV-2 infection as the primary cause of mortality decreased over time (23.8% in 2020, 20.9% in 2021 and 7.9% in 2022). On multivariable analysis, vaccination (any dose) was independently associated with lower rates of death related to SARS-CoV-2 infection (HR .15, p < .001), after adjusting for other independent predictors. A total of 172 patients were vaccinated at least with two doses at the time of death: 93% triple-vaccinated, 7% double-vaccinated. On histological analysis, vaccinated patients had a greater frequency of pneumonia severity score 0 and 1 (20.3% vs. 5.4% and 20.9% vs. 7.7%, p < .001, respectively), and a substantially lower proportion of pneumonia severity score 3 (26.2% vs. 55.1%, p < .001) compared to unvaccinated patients. COVID-19 vaccination has substantially reduced rates of death related to SARS-CoV-2 infection over time and may have the ability to mitigate lung damage.

Comparative Ability of Various Immunosuppressants as Adjuvants on the Activity of T1D Vaccine

Background: Type 1 diabetes (T1D) is an autoimmune disorder characterised by the destruction of insulin-producing beta cells in the pancreatic islets, resulting from a breakdown in immunological tolerance. Currently, T1D treatment primarily relies on insulin replacement or immunosuppressive therapies. However, these approaches often have significant drawbacks, including adverse effects, high costs, and limited long-term efficacy. Consequently, there is a pressing need for innovative immunotherapeutic strategies capable of inducing antigen-specific tolerance and protecting beta cells from autoimmune destruction. Among the various antigens, β-cell antigens like 65 kDa glutamic acid decarboxylase (GAD65) have been explored as vaccine candidates for T1D. Despite their potential, their effectiveness in humans remains modest, necessitating the use of appropriate adjuvants to enhance the vaccine’s protective effects. Methods: In this study, we evaluated the therapeutic potential of kynurenine (KYN), dexamethasone (DXMS), tacrolimus (FK506), and aluminium hydroxide (Alum) in combination with the GAD65 phage vaccine as adjuvants. Results: Our findings demonstrate that KYN, when used in conjunction with the GAD65 vaccine, significantly enhances the vaccine’s immunosuppressive effects. Compared to dexamethasone, FK506, and Alum adjuvants, KYN more effectively reduced the incidence and delayed the onset of T1D, preserved β-cell function, and promoted the induction of regulatory T cells and antigen-specific tolerance. These results suggest that KYN combined with vaccines could offer superior preventive and therapeutic benefits for T1D compared to existing treatments. Additionally, we investigated the dose-dependent effects of the GAD65 vaccine by including a low-dose group in our study. The results indicated that reducing the vaccine dose below 1010 plaque-forming units (pfu) did not confer any protective advantage or therapeutic benefit in combination with KYN. This finding underscores that 1010 pfu is the minimum effective dose for the GAD65 vaccine in achieving a protective response. In conclusion, KYN shows considerable promise as an adjuvant for the GAD65 vaccine in T1D therapy, potentially offering a more effective and durable treatment option than current immunosuppressive strategies.

Long Complications of COVID Vaccination

COVID-19 vaccination has been a critical tool in the global fight against the pandemic, offering hope for a return to normalcy. While the immediate side effects of vaccination are well-documented and generally mild, concerns around potential long-term complications have emerged. This article explores the reported long-term complications following COVID vaccination, factors influencing these outcomes, and strategies for managing and addressing them. By delving into research findings and offering recommendations, we aim to provide valuable insights for individuals navigating the complexities of post-vaccination health concerns.

Prevalence of Transfusion-Transmissible Infections Among Voluntary Blood Donors in a Tertiary Care Hospital.

Background Transfusion-transmissible infections (TTIs) pose a significant risk to blood transfusion safety, especially in low-resource settings. TTIs include infections such as HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis, and malaria. Over four years, this study assesses the seroprevalence of TTIs among voluntary blood donors at a tertiary care center. Materials and methods This retrospective observational study was conducted at the blood bank of a tertiary care center from June 2019 to December 2022. A total of 4639 voluntary blood donors were screened for TTIs, including HIV, HBV, HCV, syphilis, and malaria, using third-generation enzyme-linked immunosorbent assay (ELISA) kits and rapid diagnostic tests. The data were analyzed to evaluate the seroprevalence of each infection and its trends over the study period. Results The overall prevalence of TTIs among the 4639 donors was 68 (1.46%). The highest seroprevalence was observed for HBV, with 33 (0.71%), followed by syphilis with 22 (0.47%), HIV with nine (0.19%), and HCV with four (0.08%). No cases of malaria were detected. The prevalence of TTIs was highest in 2021, with the seroprevalence of HBV peaking at 15 (1.14%). Male donors accounted for 4412 (98%) of all donations, and the prevalence of TTIs was significantly higher among males than females. Conclusion The study highlights the importance of continuous surveillance and screening for TTIs among blood donors to ensure transfusion safety. The higher seroprevalence of HBV underscores the need for effective vaccination programs, and the disparity in gender distribution calls for strategies to encourage female blood donations. TTIs remain a public health concern, necessitating improved donor screening and public awareness.

Immune Profile in COVID-19: Unveiling TR3-56 Cells in SARS-CoV-2 Infection.

The emergence of COronaVIrus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presented a global health challenge since its identification in December 2019. With clinical manifestations ranging from mild respiratory symptoms to severe multi-organ dysfunction, COVID-19 continues to affect populations worldwide. The complex interactions between SARS-CoV-2 variants and the human immune system are crucial for developing effective therapies, vaccines, and preventive measures. Understanding these immune responses highlights the intricate nature of COVID-19 pathogenesis. This retrospective study analyzed, by flow cytometry approach, a cohort of patients infected with SARS-CoV-2 during the initial pandemic waves from 2020 to 2021. It focused on untreated individuals at the time of hospital admission and examined the presence of TR3-56 cells in their immune profiles during the anti-viral immune response. Our findings provide additional insights into the complex immunological dynamics of SARS-CoV-2 infection and highlight the potential role of TR3-56 cells as crucial components of the immune response. We suggest that TR3-56 cells could serve as valuable biomarkers for identifying more severe cases of COVID-19, aiding in the assessment and management of the disease.

Quantifying and Adjusting for Confounding From Health-Seeking Behavior and Health Care Access in Observational Research.

Health-seeking behavior and health care access (HSB/HCA) are recognized confounders in many observational studies but are not directly measurable in electronic health records. We used proxy markers of HSB/HCA to quantify and adjust for confounding in observational studies of influenza and COVID-19 vaccine effectiveness (VE). This cohort study used primary care data prelinked to secondary care and death data in England. We included individuals aged ≥66 years on 1 September 2019 and assessed influenza VE in the 2019-2020 season and early COVID-19 VE (December 2020-March 2021). VE was estimated with sequential adjustment for demographics, comorbidities, and 14 markers of HSB/HCA. Influenza vaccination in the 2019-2020 season was also considered a negative control exposure against COVID-19 before COVID-19 vaccine rollout. We included 1 991 284, 1 796 667, and 1 946 943 individuals in the influenza, COVID-19, and negative control exposure populations, respectively. Markers of HSB/HCA were positively correlated with influenza and COVID-19 vaccine uptake. For influenza, adjusting for HSB/HCA markers in addition to demographics and comorbidities increased VE against influenza-like illness from -1.5% (95% CI, -3.2% to .1%) to 7.1% (95% CI, 5.4%-8.7%) with a less apparent trend for more severe outcomes. For COVID-19, adjusting for HSB/HCA markers did not change VE estimates against infection or severe disease (eg, 2 doses of BNT162b2 against infection: 82.8% [95% CI, 78.4%-86.3%] to 83.1% [95% CI, 78.7%-86.5%]). Adjusting for HSB/HCA markers removed bias in the negative control exposure analysis (-7.5% [95% CI, -10.6% to -4.5%] vs -2.1% [95% CI, -6.0% to 1.7%] before vs after adjusting for HSB/HCA markers). Markers of HSB/HCA can be used to quantify and account for confounding in observational vaccine studies.

Protection of vaccine boosters and prior infection against mild/asymptomatic and moderate COVID-19 infection in the UK SIREN healthcare worker cohort: October 2023 to March 2024

ObjectivesBivalent original/BA.4-5 and monovalent XBB.1.5 mRNA boosters were offered to UK healthcare workers (HCWs) in autumn 2023. We aimed to estimate booster vaccine effectiveness (VE) and post-infection immunity among the SIREN HCW cohort over the subsequent 6-month period of XBB.1.5 and JN.1 variant circulation. MethodsBetween October 2023 to March 2024, 2,867 SIREN study participants tested fortnightly for SARS-CoV-2 and completed symptoms questionnaires. We used multi-state models, adjusted for vaccination, prior infection, and demographic covariates, to estimate protection against mild/asymptomatic and moderate SARS-CoV-2 infection. ResultsHalf of participants (1,422) received a booster during October 2023 (280 bivalent, 1,142 monovalent), and 536 (19%) had a PCR-confirmed infection over the study period. Bivalent booster VE was 15.1% (-55.4 to 53.6%) at 0-2 months and 4.2% (-46.4 to 37.3%) at 2-4 months post-vaccination. Monovalent booster VE was 44.2% (95% CI 21.7 to 60.3%) at 0-2 months, and 24.1% (-0.7 to 42.9%) at 2-4 months. VE was greater against moderate infection than against mild/asymptomatic infection, but neither booster showed evidence of protection after 4 months. Controlling for vaccination, compared to an infection >2 years prior, infection within the past 6 months was associated with 58.6% (30.3 to 75.4%) increased protection against moderate infection, and 38.5% (5.8 to 59.8%) increased protection against mild/asymptomatic infection. ConclusionsMonovalent XBB.1.5 boosters provided short-term protection against SARS-CoV-2 infection, particularly against moderate symptoms. Vaccine formulations which target the circulating variant may be suitable for inclusion in seasonal vaccination campaigns among HCWs.

Development and characterization of reverse genetics systems of feline infectious peritonitis virus for antiviral research

Feline infectious peritonitis (FIP) is a lethal, immune-mediated disease in cats caused by feline infectious peritonitis virus (FIPV), a biotype of feline coronavirus (FCoV). In contrast to feline enteric coronavirus (FECV), which exclusively infects enterocytes and causes diarrhea, FIPV specifically targets macrophages, resulting in the development of FIP. The transmission and infection mechanisms of this complex, invariably fatal disease remain unclear, with no effective vaccines or approved drugs for its prevention or control. In this study, a full-length infectious cDNA clone of the wild-type FIPV WSU79-1149 strain was constructed to generate recombinant FIPV (rFIPV-WT), which exhibited similar growth kinetics and produced infectious virus titres comparable to those of the parental wild-type virus. In addition, the superfold green fluorescent protein (msfGFP) and Renilla luciferase (Rluc) reporter genes were incorporated into the rFIPV-WT cDNA construct to generate reporter rFIPV-msfGFP and rFIPV-Rluc viruses. While the growth characteristics of the rFIPV-msfGFP virus were similar to those of its parental rFIPV-WT, the rFIPV-Rluc virus replicated more slowly, resulting in the formation of smaller plaques than did the rFIPV-WT and rFIPV-msfGFP viruses. In addition, by replacing the S, E, M, and ORF3abc genes with msfGFP and Rluc genes, the replicon systems repFIPV-msfGFP and repFIPV-Rluc were generated on the basis of the cDNA construct of rFIPV-WT. Last, the use of reporter recombinant viruses and replicons in antiviral screening assays demonstrated their high sensitivity for quantifying the antiviral effectiveness of the tested compounds. This integrated system promises to significantly streamline the investigation of virus replication within host cells, enabling efficient screening for anti-FIPV compounds and evaluating emerging drug-resistant mutations within the FIPV genome.

Comprehensive statistical analysis reveals significant benefits of COVID-19 vaccination in hospitalized patients: propensity score, covariate adjustment, and feature importance by permutation

BackgroundCOVID-19 vaccines effectively prevent infection and hospitalization. However, few population-based studies have compared the clinical characteristics and outcomes of patients hospitalized for COVID-19 using advanced statistical methods. Our objective is to address this evidence gap by comparing vaccinated and unvaccinated patients hospitalized for COVID-19.MethodsThis retrospective cohort included adult COVID-19 patients admitted from March 2021 to August 2022 from 27 hospitals. Clinical characteristics, vaccination status, and outcomes were extracted from medical records. Vaccinated and unvaccinated patients were compared using propensity score analyses, calculated based on variables associated with vaccination status and/or outcomes, including waves. The vaccination effect was also assessed by covariate adjustment and feature importance by permutation.ResultsFrom the 3,188 patients, 1,963 (61.6%) were unvaccinated and 1,225 (38.4%) were fully vaccinated. Among these, 558 vaccinated individuals were matched with 558 unvaccinated ones. Vaccinated patients had lower rates of mortality (19.4% vs. 33.3%), invasive mechanical ventilation (IMV-18.3% vs. 34.6%), noninvasive mechanical ventilation (NIMV-10.6% vs. 22.0%), intensive care unit admission (ICU-32.0% vs. 44.1%) vasoactive drug use (21.1% vs. 32.6%), dialysis (8.2% vs. 14.7%) hospital length of stay (7.0 vs. 9.0 days), and thromboembolic events (3.9% vs.7.7%), p < 0.05 for all. Risk-adjusted multivariate analysis demonstrated a significant inverse association between vaccination and in-hospital mortality (adjusted odds ratio [aOR] = 0.42, 95% confidence interval [CI]: 0.31–0.56; p < 0.001) as well as IMV (aOR = 0.40, 95% CI: 0.30–0.53; p < 0.001). These results were consistent in all analyses, including feature importance by permutation.ConclusionVaccinated patients admitted to hospital with COVID-19 had significantly lower mortality and other severe outcomes than unvaccinated ones during the Delta and Omicron waves. These findings have important implications for public health strategies and support the critical importance of vaccination efforts, particularly in low-income countries, where vaccination coverage remains suboptimal.