Assess Vaccine Efficacy Research Articles

Artificial intelligence – NPHIs’ role in utilizing its opportunities and addressing the risks

Abstract Issue & Problem National Public Health Institutes (NPHIs) in many countries are at the forefront of action to mitigate the impact of current and future threats to health as well as improving population health and wellbeing. Through research, collaboration, and support, NPHIs can approach these new realities together. One of the many emerging realities that NPHIs will need to engage in is how NPHIs best can utilise the powers of artificial intelligence and deal with the ethical and legal issues that come with it. Methods In preparation of IANPHI’s (International Association of National Public Health Institutes) Europe Regional network meeting in April 2024 a survey was conducted among the 42 members. 16 countries replied to questions, around e.g., 1) current applications of (generative) artificial intelligence (AI) in the work of institutes, 2) which experiences were made and 3) which measures NPHIs take to best utilize the possibilities and overcome challenges of AI technologies. Within four weeks 16 replies were shared. Lessons & Conclusions Some institutes have not yet adopted AI, while others report multiple applications but the primary areas of application vary considerably among Europe. Applications include summarizing and reformatting text; translation; transcribing and documenting meetings; search information in documents or databases; coding; creating visuals; literature review; surveillance of infectious diseases; disease forecasting; analysis of transmission dynamics; vaccine efficacy assessment and development; image recognition; diagnosis and prediction of diseases from medical datasets; text mining; symptom extraction; social listening; prediction of nitrate concentration in groundwater; drug analysis and measuring psychological resilience in social crisis. Key messages • AI poses opportunities and risks for public health and work of national public health institutes and capacity building initiatives are essential. • IANPHI decided to develop a joint framework for the use of AI in its member organisations with a focus on research and responsible use.

Immunogenicity and Protectivity of Sputnik V Vaccine in hACE2-Transgenic Mice against Homologous and Heterologous SARS-CoV-2 Lineages Including Far-Distanced Omicron BA.5

Background: The SARS-CoV-2 virus continuously acquires mutations, leading to the emergence of new variants. Notably, the effectiveness of global vaccination efforts has significantly declined with the rise and spread of the B.1.1.529 (Omicron) variant. Methods: The study used virological, immunological and histological research methods, as well as methods of working with laboratory animals. In this study, we evaluated the Gam-COVID-Vac (Sputnik V), an adenoviral vaccine developed by the N.F. Gamaleya National Research Center for Epidemiology and Microbiology, and conducted experiments on hemizygous K18-ACE2-transgenic F1 mice. The variants studied included B.1.1.1, B.1.1.7, B.1.351, B.1.1.28/P.1, B.1.617.2, and B.1.1.529 BA.5. Results: Our findings demonstrate that the Sputnik V vaccine elicits a robust humoral and cellular immune response, effectively protecting vaccinated animals from challenges posed by various SARS-CoV-2 variants. However, we observed a notable reduction in vaccine efficacy against the B.1.1.529 (Omicron BA.5) variant. Conclusions: Our results indicate that ongoing monitoring of emerging mutations is crucial to assess vaccine efficacy against new SARS-CoV-2 variants to identify those with pandemic potential. If protective efficacy declines, it will be imperative to develop new vaccines tailored to current variants of the virus.

B-043 Q-nab™ Igg kit: verification and validation of a novel cell-free quantitative neutralizing antibody assay

Abstract Background As the world exits the COVID-19 pandemic era, it is very important to assess population-level and individual seroprotectivity against multiple circulating and emerging SARS-CoV-2 strains, especially in vulnerable populations. Current serological measurements for neutralizing antibodies (NAbs) are either done using complex and time-intensive pseudovirus- or micro-neutralization assays or as a high throughput competitive ELISA assay. These assays, by design, cannot be multiplexed to measure NAb titers against multiple strains and suffer from a limited dynamic range. The Q-NAb IgG Tests, which rely on blocking the non-neutralizing antibodies (NNAbs) using a novel fusion protein, were developed and validated to quantitatively measure NAb titer against the SARS-CoV-2 strains used to develop the first two mRNA vaccines viz. ancestral and BA.4/5 strains. Methods The Q-NAb assay measures the NAb titer in a sample by first sequestering the NNAbs using the fusion protein (made by covalently coupling SARS-CoV-2 BA.4/5 RBD and h-ACE2 protein) thereby enriching the NAbs in the sample. Variant-specific NAbs are then detected using an indirect ELISA where the wells are coated with the variant RBD and yield a signal that is directly proportional to the concentration of NAb. Clinical samples from subjects that have either had a SARS-CoV-2 infection (N=27), taken the initial vaccine series (N=123) and/or the bivalent booster (N=151) and pre-pandemic samples (N=29) were commercially sourced. Q-NAb NAb titers were measured using the ancestral and BA.4/5 kits and were compared against corresponding MN50 values using both parametric and non-parametric models. Single-site precision, low-end sensitivity, dilutional linearity, and interference screening of Q-NAb IgG Kits were evaluated in accordance with appropriate CLSI guidelines. Traceability and total uncertainty of the Q-NAb IgG Kits (Ancestral and BA.4/5) to WHO International Standard 21/340 and 21/338 respectively was established using a calibration hierarchy adapted from ISO 17511:2020. Results Both the ancestral and BA.4/5 Q-NAb IgG Test Kits correlated with MN50 titers with a Spearman correlation coefficient of 0.90 and 0.89 respectively. The total uncertainty in traceability of calibration to WHO International standards 21/340 and 21/338 was found to be less than 10% for both tests. Single site precision across the assay range for BA.4/5 kit was found to be 6-10% with a limit of quantitation of 312 IU/mL. Assays exhibited dilutional linearity across their respective dynamic range and had no significant interference from common endogenous and exogenous substances. Conclusions We have successfully validated the novel Q-NAb IgG neutralization assay platform as individual assays for measuring neutralizing titers against ancestral and BA.4/5 SARS-CoV-2 strains. The assays have expanded dynamic range, excellent analytical performance and correlation to accepted gold-standard microneutralization assays. Both assays are calibrated and traceable to WHO international standards, thereby enabling the compilation and comparison of data from multiple clinical cohorts run across multiple laboratories. The design of the Q-NAb IgG Test kit makes it amenable to multiplexing (for example, on an MSD platform) to assess neutralization titers against multiple variants at the same time. Such a multiplexed platform can be used to assess vaccine efficacy and seroprotection against multiple variants including emerging variants.

Phylodynamics of high pathogenicity avian influenza virus in Bangladesh identifying domestic ducks as the amplifying host reservoir

ABSTRACT High pathogenicity avian influenza (HPAI) virus H5N1 first emerged in Bangladesh in 2007. Despite the use of vaccines in chickens since 2012 to control HPAI, HPAI H5Nx viruses have continued to infect poultry, and wild birds, resulting in notable mass mortalities in house crows (Corvus splendens). The first HPAI H5Nx viruses in Bangladesh belonged to clade 2.2.2, followed by clade 2.3.4.2 and 2.3.2.1 viruses in 2011. After the implementation of chicken vaccination in 2012, these viruses were mostly replaced by clade 2.3.2.1a viruses and more recently clade 2.3.4.4b and h viruses. In this study, we reconstruct the phylogenetic history of HPAI H5Nx viruses in Bangladesh to evaluate the role of major host species in the maintenance and evolution of HPAI H5Nx virus in Bangladesh and reveal the role of heavily impacted crows in virus epidemiology. Epizootic waves caused by HPAI H5N1 and H5N6 viruses amongst house crows occurred annually in winter. Bayesian phylodynamic analysis of clade 2.3.2.1a revealed frequent bidirectional viral transitions between domestic ducks, chickens, and house crows that was markedly skewed towards ducks; domestic ducks might be the source, or reservoir, of HPAI H5Nx in Bangladesh, as the number of viral transitions from ducks to chickens and house crows was by far more numerous than the other transitions. Our results suggest viral circulation in domestic birds despite vaccination, with crow epizootics acting as a sentinel. The vaccination strategy needs to be updated to use more effective vaccinations, assess vaccine efficacy, and extension of vaccination to domestic ducks, the key reservoir.

Comparative Analysis of HPV16 Variants in the Untranslated Regulatory Region, L1, and E6 Genes among Vaccinated and Unvaccinated Young Women: Assessing Vaccine Efficacy and Viral Diversity.

HPV16 is occasionally detected in vaccinated women who received the bivalent HPV16/18 vaccine, usually at low viral loads. This study explored potential differences in HPV16 variants between vaccinated and unvaccinated women. HPV16-postive viral loads were detected in 1.9% (17/875) and 13% (162/760) of vaccinated and unvaccinated women, respectively, showcasing the vaccine's high efficacy. The L1, E6, and URR regions of HPV16 were sequenced from genital swabs from 16 vaccinated and 25 unvaccinated women in the HAVANA (HPV Among Vaccinated And Non-vaccinated Adolescents) study. The majority of HPV16 variants from vaccinated and unvaccinated women clustered similarly with sub-lineages A1 and A2. Additionally, a separate cluster within lineage A was found, with the variants sharing the L1-located SNP A753G (synonymous) and the URR-located SNP T340C, which did not occur in the other variants. Furthermore, four variants from vaccinated women had relatively long branches, but were not characterized by specific SNPs. The frequency of G712A in the URR was the only SNP observed to be marginally higher among vaccinated women than unvaccinated women. Non-synonymous SNPs T266A in the FG-loop of L1 and L83V in E6 were common among variants from vaccinated and unvaccinated women, but present in similar frequencies. In conclusion, the detection of HPV16 in vaccinated (and unvaccinated) women seemed to be the result of random circulation within this study population.

Assessing vaccine efficacy for infectious diseases with variable immunity using a mathematical model

This study introduces an SIRS compartmental mathematical model encompassing vaccination and variable immunity periods for infectious diseases. I derive a basic reproduction number formula and assess the local and global stability of disease-free and the local stability of the endemic equilibria. I demonstrate that the basic reproduction number in the presence of a vaccine is highly sensitive to the rate of immunity loss, and even a slight reduction in this rate can significantly contribute to disease control. Additionally, I have derived a formula to calculate the critical efficacy period required for a vaccine to effectively manage and control the disease.The analysis conducted for the model suggests that increasing the vaccine’s immunity duration (efficacy) decelerates disease dynamics, leading to reduced rates of reinfection and less severe disease outcomes. Furthermore, this delay contributes to a decrease in the basic reproduction number (R0\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$R_0$$\\end{document}), thus facilitating more rapid disease control efforts.

Evaluation of SARS-Cov-2 neutralizing antibody among Sinopharm Vero Cell (BBIBP-CorV) vaccinated medical students.

Information regarding seropositivity and vaccine efficacy among medical students is scarce. This study aims to detect the status of SARS-CoV-2 neutralizing antibodies among the Sinopharm's Vero Cell (BBIBP-CorV) vaccinated medical students. A prospective, cross-sectional study was carried out among medical students of Gandaki Medical College Teaching Hospital, Pokhara, Nepal from March through August 2022. The level of SARS-CoV-2 serum- neutralizing IgG antibody was measured and its relation with participants' age and sex, duration of vaccination, and any comorbid condition was determined. A total of 110 medical students were included in the final analysis, the majority being females (65.5%) and the mean age is 23.1 ± 3.2years. Most of the students (96.4%) had neutralizing antibodies against SARS-CoV-2. Among the 29 (26.36%) students who received a booster dose, the positivity rate was 100%. The mean IgG levels were 9.57 ± 9.58μg/ml and 2.91 ± 2.47μg/ml among students receiving an additional booster dose and among those not receiving it, respectively. In the cohort receiving a booster dose of the vaccine, the average value of neutralizing IgG antibodies was high. In contrast, the ones not receiving it, the titers were low and showed a declining trend. Though the dose strategy of the Sinopharm vaccine is effective, booster vaccination may be an important strategy to ensure protection among medical students, who are at high risk of COVID-19 due to constant patient exposure during their training. Further studies should assess vaccine efficacy among individuals who received other vaccines as well.

An injectable subunit vaccine containing Elongation Factor Tu and Heat Shock Protein 70 partially protects American bison from Mycoplasma bovis infection.

Mycoplasma bovis (M. bovis) is the etiologic agent of high mortality epizootics of chronic respiratory disease in American bison (Bison bison). Despite the severity of the disease, no efficacious commercial vaccines have been licensed for the prevention of M. bovis infection in bison. Elongation factor thermal unstable (EFTu) and Heat Shock Protein 70 (Hsp70, DnaK) are highly conserved, constitutively expressed proteins that have previously been shown to provide protection against M. bovis infection in cattle. To assess the suitability of EFTu and Hsp70 as vaccine antigens in bison, the immune response to and protection conferred by an injectable, adjuvanted subunit vaccine comprised of recombinantly expressed EFTu and Hsp70 was evaluated. Vaccinates developed robust antibody and cellular immune responses against both EFTu and Hsp70 antigens. To assess vaccine efficacy, unvaccinated control and vaccinated bison were experimentally challenged with bovine herpes virus-1 (BHV-1) 4 days prior to intranasal infection with M. bovis. Vaccinated bison displayed reductions in joint infection, lung bacterial loads, and lung lesions compared to unvaccinated controls. Together, these results showed that this subunit vaccine reduced clinical disease and bacterial dissemination from the lungs in M. bovis challenged bison and support the further development of protein subunit vaccines against M. bovis for use in bison.

Immunological Insights: A Multicenter Longitudinal Study on Humoral Response to COVID-19 Vaccines in Greece

Vaccination has emerged as the most effective tool in the battle against COVID-19. To optimize vaccination protocols, a deeper understanding of the immune response to vaccination, including influential factors and its duration, is essential. This study aimed to assess the humoral response in vaccinated individuals with or without prior SARS-CoV-2 infection. A prospective observational study was conducted across 14 private healthcare structures in Greece. Anti-spike IgG titers were measured at different timepoints following the initial vaccination and booster doses of the BNT162b2, mRNA-1273, ChAdOx1 nCoV-19, and Ad26.COV2.S vaccines. A total of 505 participants were included in the first phase, evaluating the humoral response after the initial vaccination, and 311 participants were involved in the second phase, assessing the effects of booster vaccination. All vaccines elicited high anti-S IgG titers initially, followed by a subsequent decline that was addressed by the booster vaccination. The humoral response was sustained up to one year after the booster vaccination. mRNA vaccines induced higher anti-S IgG titers compared to vector vaccines, with mRNA-1273 eliciting higher titers than BNT162b2. Vaccination resulted in higher antibody titers than natural infection alone; however, convalescent patients who received vaccination had significantly higher anti-S IgG titers compared to those who received the booster vaccine without previous SARS-CoV-2 infection. Lower antibody titers were observed in men and older patients (>51.5 years old), as well as smokers, although the decline rate was lower in these subgroups. These results underscore the importance of booster doses and reveal the potential influence of age, gender, smoking habits, and vaccine type on varying humoral responses. Long-term monitoring of antibody persistence, evaluation of cellular immune responses, and assessment of vaccine efficacy against emerging variants should be considered to enhance our understanding of immunity dynamics and inform vaccine development and deployment strategies.

A Simplistic Label‐Free Electrochemical Immunosensing Approach for Rapid and Sensitive Detection of Anti‐SARS‐COV‐2 Nucleocapsid Antibodies

AbstractRapid and precise detection of SARS‐CoV‐2 antibodies is paramount for effective outbreak monitoring and vaccine efficacy assessment. While existing approaches for antibody detection often rely on complex electrochemical immunosensing with nanomaterial functionalization targeting S‐protein antibodies, their limitations in sensitivity and complexity have hindered widespread application. Here, we present a simplistic immunosensing platform designed for the rapid, and precise detection of SARS‐CoV‐2 specific IgG and Nucleocapsid antibodies. Notably, this study marks only the second exploration of SARS‐CoV‐2 N‐protein antibody detection. The platform utilizes traditional self‐assembled monolayers to establish selective bio‐affinity between SARS‐CoV‐2 specific Nucleocapsid antibodies and a gold electrode functionalized with the N‐protein antigen. Interestingly, despite the absence of nanomaterial functionalization, the developed platform achieves sensitivity comparable to existing sensors across a wide detection range (0.025 to 1 ng/mL) with an impressive limit of detection (0.019 ng/mL). The simplicity of the approach, relying solely on immunocomplex reactions, underscores that effective binding efficiency may be achieved in the absence of complex functionalization and determines its affordability, specificity, and high sensitivity. By eliminating the need for additional functionalization steps, the platform offers a streamlined solution for SARS‐CoV‐2 antibody detection and demonstrates the possibility of N‐protein antibody detection as a promising avenue for widespread application in SARS‐CoV‐2 outbreak monitoring and vaccine efficacy assessment particularly in underdeveloped regions.

SARS-CoV-2 Neutralization Assays Used in Clinical Trials: A Narrative Review.

Since the emergence of COVID-19, extensive research efforts have been undertaken to accelerate the development of multiple types of vaccines to combat the pandemic. These include inactivated, recombinant subunit, viral vector, and nucleic acid vaccines. In the development of these diverse vaccines, appropriate methods to assess vaccine immunogenicity are essential in both preclinical and clinical studies. Among the biomarkers used in vaccine evaluation, the neutralizing antibody level serves as a pivotal indicator for assessing vaccine efficacy. Neutralizing antibody detection methods can mainly be classified into three types: the conventional virus neutralization test, pseudovirus neutralization test, and surrogate virus neutralization test. Importantly, standardization of these assays is critical for their application to yield results that are comparable across different laboratories. The development and use of international or regional standards would facilitate assay standardization and facilitate comparisons of the immune responses induced by different vaccines. In this comprehensive review, we discuss the principles, advantages, limitations, and application of different SARS-CoV-2 neutralization assays in vaccine clinical trials. This will provide guidance for the development and evaluation of COVID-19 vaccines.

Profiling of Early Immune Responses to Vaccination Using THP-1-Derived Dendritic Cells.

The COVID-19 pandemic has made assessing vaccine efficacy more challenging. Besides neutralizing antibody assays, systems vaccinology studies use omics technology to reveal immune response mechanisms and identify gene signatures in human peripheral blood mononuclear cells (PBMCs). However, due to their low proportion in PBMCs, profiling the immune response signatures of dendritic cells (DCs) is difficult. Here, we develop a predictive model for evaluating early immune responses in dendritic cells. We establish a THP-1-derived dendritic cell (TDDC) model and stimulate their maturation in vitro with an optimal dose of attenuated yellow fever 17D (YF-17D). Transcriptomic analysis reveals that type I interferon (IFN-I)-induced immunity plays a key role in dendritic cells. IFN-I regulatory biomarkers (IRF7, SIGLEC1) and IFN-I-inducible biomarkers (IFI27, IFI44, IFIT1, IFIT3, ISG15, MX1, OAS2, OAS3) are identified and validated in vitro and in vivo. Furthermore, we apply this TDDC approach to various types of vaccines, providing novel insights into their early immune response signatures and their heterogeneity in vaccine recipients. Our findings suggest that a standardizable TDDC model is a promising predictive approach to assessing early immunity in DCs. Further research into vaccine efficacy assessment approaches on various types of immune cells could lead to a systemic regimen for vaccine development in the future.

Safety of a controlled human infection model of tuberculosis with aerosolised, live-attenuated Mycobacterium bovis BCG versus intradermal BCG in BCG-naive adults in the UK: a dose-escalation, randomised, controlled, phase 1 trial

Mycobacterium tuberculosis is the main causative agent of tuberculosis. BCG, the only licensed vaccine, provides inadequate protection against pulmonary tuberculosis. Controlled human infection models are useful tools for vaccine development. We aimed to determine a safe dose of aerosol-inhaled live-attenuated Mycobacterium bovis BCG as a surrogate for M tuberculosis infection, then compare the safety and tolerability of infection models established using aerosol-inhaled and intradermally administered BCG. This phase 1 controlled human infection trial was conducted at two clinical research facilities in the UK. Healthy, immunocompetent adults aged 18-50 years, who were both M tuberculosis-naive and BCG-naive and had no history of asthma or other respiratory diseases, were eligible for the trial. Participants were initially enrolled into group 1 (receiving the BCG Danish strain); the trial was subsequently paused because of a worldwide shortage of BCG Danish and, after protocol amendment, was restarted using the BCG Bulgaria strain (group 2). After a dose-escalation study, during which participants were sequentially allocated to receive either 1 × 103, 1 × 104, 1 × 105, 1 × 106, or 1 × 107 colony-forming units (CFU) of aerosol BCG, the maximum tolerated dose was selected for the randomised controlled trial. Participants in this trial were randomly assigned (9:12), by variable block randomisation and using sequentially numbered sealed envelopes, to receive aerosol BCG (1 × 107 CFU) and intradermal saline or intradermal BCG (1 × 106 CFU) and aerosol saline. Participants were masked to treatment allocation until day 14. The primary outcome was to compare the safety of a controlled human infection model based on aerosol-inhaled BCG versus one based on intradermally administered BCG, and the secondary outcome was to evaluate BCG recovery in the airways of participants who received aerosol BCG or skin biopsies of participants who received intradermal BCG. BCG was detected by culture and by PCR. The trial is registered at ClinicalTrials.gov, NCT02709278, and is complete. Participants were assessed for eligibility between April 7, 2016, and Sept 29, 2018. For group 1, 15 participants were screened, of whom 13 were enrolled and ten completed the study; for group 2, 60 were screened and 33 enrolled, all of whom completed the study. Doses up to 1 × 107 CFU aerosol-inhaled BCG were sufficiently well tolerated. No significant difference was observed in the frequency of adverse events between aerosol and intradermal groups (median percentage of solicited adverse events per participant, post-aerosol vs post-intradermal BCG: systemic 7% [IQR 2-11] vs 4% [1-13], p=0·62; respiratory 7% [1-19] vs 4% [1-9], p=0·56). More severe systemic adverse events occurred in the 2 weeks after aerosol BCG (15 [12%] of 122 reported systemic adverse events) than after intradermal BCG (one [1%] of 94; difference 11% [95% CI 5-17]; p=0·0013), but no difference was observed in the severity of respiratory adverse events (two [1%] of 144 vs zero [0%] of 97; 1% [-1 to 3]; p=0·52). All adverse events after aerosol BCG resolved spontaneously. One serious adverse event was reported-a participant in group 2 was admitted to hospital to receive analgesia for a pre-existing ovarian cyst, which was deemed unrelated to BCG infection. On day 14, BCG was cultured from bronchoalveolar lavage samples after aerosol infection and from skin biopsy samples after intradermal infection. This first-in-human aerosol BCG controlled human infection model was sufficiently well tolerated. Further work will evaluate the utility of this model in assessing vaccine efficacy and identifying potential correlates of protection. Bill & Melinda Gates Foundation, Wellcome Trust, National Institute for Health Research Oxford Biomedical Research Centre, Thames Valley Clinical Research Network, and TBVAC2020.

Diverse animal models for Chlamydia infections: unraveling pathogenesis through the genital and gastrointestinal tracts.

Chlamydia trachomatis is responsible for infections in various mucosal tissues, including the eyes, urogenital, respiratory, and gastrointestinal tracts. Chronic infections can result in severe consequences such as blindness, ectopic pregnancy, and infertility. The underlying mechanisms leading to these diseases involve sustained inflammatory responses, yet thorough comprehension of the underlying mechanisms remains elusive. Chlamydial biologists employ in multiple methods, integrating biochemistry, cell biology, and genetic tools to identify bacterial factors crucial for host cell interactions. While numerous animal models exist to study chlamydial pathogenesis and assess vaccine efficacy, selecting appropriate models for biologically and clinically relevant insights remains a challenge. Genital infection models in animals have been pivotal in unraveling host-microbe dynamics, identifying potential chlamydial virulence factors influencing genital pathogenicity. However, the transferability of this knowledge to human pathogenic mechanisms remains uncertain. Many putative virulence factors lack assessment in optimal animal tissue microenvironments, despite the diverse chlamydial infection models available. Given the propensity of genital Chlamydia to spread to the gastrointestinal tract, investigations into the pathogenicity and immunological impact of gut Chlamydia become imperative. Notably, the gut emerges as a promising site for both chlamydial infection vaccination and pathogenesis. This review elucidates the pathogenesis of Chlamydia infections and delineates unique features of prevalent animal model systems. The primary focus of this review is to consolidate and summarize current animal models utilized in Chlamydia researches, presenting findings, discussions on their contributions, and suggesting potential directions for further studies.

Inactivated Aeromonas salmonicida impairs adaptive immunity in lumpfish (Cyclopterus lumpus).

Aeromonas salmonicida, a widely distributed aquatic pathogen causing furunculosis in fish, exhibits varied virulence, posing challenges in infectious disease and immunity studies, notably in vaccine efficacy assessment. Lumpfish (Cyclopterus lumpus) has become a valuable model for marine pathogenesis studies. This study evaluated several antigen preparations against A. salmonicida J223, a hypervirulent strain of teleost fish, including lumpfish. The potential immune protective effect of A. salmonicida bacterins in the presence and absence of the A-layer and extracellular products was tested in lumpfish. Also, we evaluated the impact of A. salmonicida outer membrane proteins (OMPs) and iron-regulated outer membrane proteins (IROMPs) on lumpfish immunity. The immunized lumpfish were intraperitoneally (i.p.) challenged with 104 A. salmonicida cells/dose at 8 weeks-post immunization (wpi). Immunized and non-immunized fish died within 2 weeks post-challenge. Our analyses showed that immunization with A. salmonicida J223 bacterins and antigen preparations did not increase IgM titres. In addition, adaptive immunity biomarker genes (e.g., igm, mhc-ii and cd4) were down-regulated. These findings suggest that A. salmonicida J223 antigen preparations hinder lumpfish immunity. Notably, many fish vaccines are bacterin-based, often lacking efficacy evaluation. This study offers crucial insights for finfish vaccine approval and regulations.

Re-evaluating efficacy of vaccines against highly pathogenic avian influenza virus in poultry: A systematic review and meta-analysis

The global spread of highly pathogenic avian influenza (HPAI) A (H5N1) clade 2.3.4.4b virus since 2021 necessitates a re-evaluation of the role of vaccination in controlling HPAI outbreaks among poultry, which has been controversial because of the concern of silent spread with viral mutation and spillover to human. We systematically reviewed and meta-analyzed all existing data from experimental challenge trials to assess the efficacy of HPAI vaccines against mortality in specific pathogen free (SPF) chickens, with evaluation of the certainty of evidence (CoE) using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Out of 223 screened publications, 46 trials met our eligibility criteria. Inactivated vaccines showed an efficacy of 95% (risk ratio [RR] = 5% [95% CI: 1% to 17%], I2 = 0%, CoE high) against homologous strains and an efficacy of 78% (RR = 22% [95% CI: 14% to 37%], I2 = 18%, CoE high) against heterologous strains (test for subgroup difference p = 0.02). Live recombinant vaccines exhibited the highest efficacy at 97% (RR = 3% [95% CI: 1% to 13%], I2 = 0%, CoE high). Inactivated recombinant vaccines had an overall efficacy of 90% (RR = 10% [95% CI: 6% to 16%], I2 = 47%, CoE high). Commercial vaccines showed an overall efficacy of 91% (RR = 9% [95% CI: 5% to 17%], I2 = 23%, CoE high), with 96% efficacy (RR = 4% [95% CI: 1% to 21%], I2 = 0%, CoE high) against homologous strains and 90% efficacy (RR = 10% [95% CI: 5% to 20%], I2 = 31%, CoE moderate) against heterologous strains. Our systematic review offers an updated and unbiased assessment of vaccine efficacy against HPAI-related mortality, providing timely and crucial information for re-evaluating the role of vaccination in poultry avian influenza control policy amist the global HPAI outbreak post-2021.

In Vitro Evaluation of Effect of Storage Time on Immunogenicity of the 10-Valent Pneumococcal Conjugate Vaccine Using Baby Rabbit Complement & HL-60 Cells

Background: The efficacy and effectiveness of a vaccine is influenced by several factors including storage duration. Additionally, vaccines may be sufficiently administered but functionality of antibody generated may be hampered with by other factors such as nutritional status of the patient. As such, one of the ways of assessing vaccine efficacy is assessing the functionality of the antibodies generated. The 10v-PCV is a highly effective vaccine used to prevent invasive pneumococcal diseases in children. However, here in Kenya, cases of pneumococcal diseases are high and challenging to treat. This study thus aimed to evaluate the effect of storage of PCV-10 storage time on the functionality of Abs generated. Methodology; An in vitro experimental research design was employed for this study. opsonophagocytic activity assay using HL-60 Cells & Baby rabbit complement was used to assess whether or not the Pneumococci Serotype IgG antibodies elicited following administration with 10v-PCV vaccine are functional. Only 10v-PCV vaccine with same production date were procured. Twenty experimental rabbits of same gender were procured and used injected intraperitoneally with 3 doses of 100µl (0.34g) of 10v-PCV vaccine after every four weeks. Antibody functionality was then assessed using the opsonophagocytic activity assay method. Results: An average of 28.9% of pneumococcus exposed to the vaccine-induced secreted antibodies were killed by the pneumococcal IgG antibody. The highest percentage of number of bacteria killed was achieved after the 3rd dose of vaccination. There was no significant influence of storage duration on opsonophagocytic activity of generated antibodies. Conclusion: Storing of 10v-PCV vaccine up to 12 weeks does not significantly affect the opsonophagocytic activity of pneumococcal IgG antibodies.

Experimental Animal Models for Influenza/Flu Virus Vaccine Development

Objectives: The objective of this review is to explore the different animal models used in the development of Influenza / Flu Virus Vaccine as well as some important guidelines adhered to it.
 Methods: Laboratory animal models are widely used in the preclinical evaluation of potential vaccines and antiviral compounds to investigate the safety and efficacy of the vaccine or compound in preventing or moderating infection, disease, or secondary transmission. Animal models must also represent humans in terms of similarity of clinical signs, histopathological changes, virus growth kinetics, or transmission. Common animal models for influenza virus vaccine testing include mice, ferrets, and non-human primates. These models help researchers assess vaccine efficacy, immune response, and potential side effects before advancing to human trials. Animal models play a crucial role in the development and testing of influenza vaccines, as they help researchers examine potential side effects and adverse reactions, evaluate the efficacy of vaccines, study the immune response elicited by vaccines, understand the pathogenesis of influenza virus infection, and predict the potential impact of emerging strains. They also help test various vaccine platforms and delivery methods, and compare the effectiveness of different vaccine formulations in animals to identify promising candidates for further human trials.
 Results: We have discussed in detail the various animal models such as Chick embryo model for the development of influenza virus vaccine and mice, ferrets, guinea pig and non-human primates etc. used for the evaluation of safety and therapeutic effectiveness.
 Conclusion: As we have discussed various animal models, their merits, demerits etc. for the evaluation of safety and effectiveness of influenza virus vaccine and expect that these will help for the young researchers to carry out their vaccine research using suitable animal models.
 Keywords: influenza virus, vaccine development, mouse models, ferret model, guinea pig model, cotton rat model

Controlled human infection study underpins efficacy of the tetravalent live-attenuated dengue vaccine TV005.

Dengue fever, caused by four distinct serotypes of the dengue virus (DENV1-4), poses a public health concern for much of the world. The NIH's Laboratory of Infectious Diseases at the National Institute of Allergy and Infectious Diseases (NIAID) has developed a series of single-dose, live-attenuated tetravalent DENV vaccines, including TV005. However, phase III trials require a lengthy three-to-five year follow-up. In contrast, controlled human infection models (CHIMs) offer a faster means to assess vaccine efficacy for any of the four serotypes. In this issue of the JCI, Pierce, Durbin, and colleagues conducted a CHIM study with attenuated DENV2 and DENV3 challenge viruses in individuals six months after vaccination with TV005. The TV005 vaccine was well tolerated and effectively protected all vaccinated individuals from viremia and rash during challenges with DENV2 or DENV3. Notably, vaccine recipients also showed serotype-specific efficacy. While long-term studies are still needed, these findings represent an important step in providing protection against dengue virus.

Standardised quantitative assays for anti-SARS-CoV-2 immune response used in vaccine clinical trials by the CEPI Centralized Laboratory Network: a qualification analysis

Accurate quantitation of immune markers is crucial for ensuring reliable assessment of vaccine efficacy against infectious diseases. This study was designed to confirm standardised performance of SARS-CoV-2 assays used to evaluate COVID-19 vaccine candidates at the initial seven laboratories (in North America, Europe, and Asia) of the Coalition for Epidemic Preparedness Innovations (CEPI) Centralized Laboratory Network (CLN). Three ELISAs (pre-spike protein, receptor binding domain, and nucleocapsid), a microneutralisation assay (MNA), a pseudotyped virus-based neutralisation assay (PNA), and an IFN-γ T-cell ELISpot assay were developed, validated or qualified, and transferred to participating laboratories. Immune responses were measured in ELISA laboratory units (ELU) for ELISA, 50% neuralisation dilution (ND50) for MNA, 50% neutralisation titre (NT50) for PNA, and spot-forming units for the ELISpot assay. Replicate assay results of well characterised panels and controls of blood samples from individuals with or without SARS-CoV-2 infection were evaluated by geometric mean ratios, standard deviation, linear regression, and Spearman correlation analysis for consistency, accuracy, and linearity of quantitative measurements across all laboratories. High reproducibility of results across all laboratories was demonstrated, with interlaboratory precision of 4·1-7·7% coefficient of variation for all three ELISAs, 3·8-19·5% for PNA, and 17·1-24·1% for MNA, over a linear range of 11-30 760 ELU per mL for the three ELISAs, 14-7876 NT50 per mL for PNA, and 21-25 587 ND50 per mL for MNA. The MNA was also adapted for detection of neutralising antibodies against the major SARS-CoV-2 variants of concern. The results of PNA and MNA (r=0·864) and of ELISA and PNA (r=0·928) were highly correlated. The IFN-γ ELISpot interlaboratory variability was 15·9-49·9% coefficient of variation. Sensitivity and specificity were close to 100% for all assays. The CEPI CLN provides accurate quantitation of anti-SARS-CoV-2 immune response across laboratories to allow direct comparisons of different vaccine formulations in different geographical areas. Lessons learned from this programme will serve as a model for faster responses to future pandemic threats and roll-out of effective vaccines. CEPI.