Vaccine Efficacy Research Articles

Predicting Efficacies of Fractional Doses of Vaccines by Using Neutralizing Antibody Levels: Systematic Review and Meta-Analysis.

With the emergence of SARS-CoV-2 variants that have eluded immunity from vaccines and prior infections, vaccine shortages and vaccine effectiveness pose unprecedented challenges for governments in expanding booster vaccination programs. The fractionation of vaccine doses might be an effective strategy for helping society to face these challenges, as fractional doses may have efficacies comparable with those of the standard doses. This study aims to investigate the relationship between vaccine immunogenicity and protection and to project efficacies of fractional doses of vaccines for COVID-19 by using neutralizing antibody levels. In this study, we analyzed the relationship between in vitro neutralization levels and the observed efficacies against both asymptomatic infection and symptomatic infection, using data from 13 studies of 10 COVID-19 vaccines and from convalescent cohorts. We further projected efficacies for fractional doses, using neutralization as an intermediate variable, based on immunogenicity data from 51 studies included in our systematic review. In comparisons with the convalescent level, vaccine efficacy against asymptomatic infection and symptomatic infection increased from 8.8% (95% CI 1.4%-16.1%) to 71.8% (95% CI 63%-80.7%) and from 33.6% (95% CI 23.6%-43.6%) to 98.6% (95% CI 97.6%-99.7%), respectively, as the mean neutralization level increased from 0.1 to 10 folds of the convalescent level. Additionally, mRNA vaccines provided the strongest protection, which decreased slowly for fractional dosing with dosages between 50% and 100% of the standard dose. We also observed that although vaccine efficacy increased with the mean neutralization level, the rate of this increase was slower for vaccine efficacy against asymptomatic infection than for vaccine efficacy against symptomatic infection. Our results are consistent with studies on immune protection from SARS-CoV-2 infection. Based on our study, we expect that fractional-dose vaccination could provide partial immunity against SARS-CoV-2 and its variants. Our findings provide a theoretical basis for the efficacy of fractional-dose vaccines, serving as reference evidence for implementing fractional dosing vaccine policies in areas facing vaccine shortages and thereby mitigating disease burden. Fractional-dose vaccination could be a viable vaccination strategy comparable to full-dose vaccination and deserves further exploration.

Immunoprotective efficacy of aqueous monovalent vaccine, turmeric (curcuma longa) rhizome and soursop (annona muricata) leaves against Pseudomonas aeruginosa infection in African sharptooth catfish (clarias gariepinus) fingerlings

ABSTRACT This study evaluated the efficacy of aqueous monovalent vaccine (AqMV) and adjuvant monovalent vaccine (AdMV), different levels of soursop leaves (SL), and turmeric rhizome (TR) on growth performance, immune response, and disease resistance of African sharptooth catfish (Clarias gariepinus) fingerlings against Pseudomonas aeruginosa. The experimental diet consists of control (without vaccine, soursop leaves and turmeric rhizome), AqMV2, AdMV3, TR4 (0.5), TR5 (1.0), TR6 (2.0), SL7 (0.5), SL8 (1.0) and SL9 (2.0). Fish were exposed to 4.85 log10 CFU/ml P. aeruginosa of 24 h old culture intraperitoneally after feeding trial with relative level of protection recorded at 28 days of post-infection. The results revealed that fish fed with treated diets showed increased (p < .05) weight gain, feed conversion ratio, nitrogen metabolism, white blood cell, globulin, total protein and blood performance and better relative level of protection compared to the control. The microbial loads in fish samples (muscle, spleen and kidney) were reduced (p < .05) in the treatments when compared to the control at 4-week post-infection. These results suggest that inactivated aqueous monovalent vaccine, soursop leaves and turmeric rhizome could be effective against P. aeruginosa infection in fish farming.

Comparative safety and efficacy of autogenous vaccine administrated by different routes against furunculosis caused by Aeromonas salmonicida sub. salmonicida in large Rainbow trout (Oncorhynchus mykiss)

The development and growth of fish farming are hindered by viral and bacterial infectious diseases, which necessitate effective disease control measures. Furunculosis, primarily caused by Aeromonas salmonicida, stands out as a significant bacterial disease affecting salmonid fish farms, particularly rainbow trout. Vaccination has emerged as a crucial tool in combating this disease. The objective of this experiment was to assess and compare the efficacy and duration of different vaccine protocols against furunculosis in large trout under controlled rearing conditions, utilizing single and booster administrations via intraperitoneal, oral, and immersion routes. Among the various vaccination protocols tested, only those involving intraperitoneal injection, administered at least once, proved truly effective in preventing the expression of clinical signs of furunculosis and reducing mortality rates. A single intraperitoneal administration provided protection for up to 2352 degree-days, equivalent to approximately 5 months in water at 16°C. However, intraperitoneal vaccination may lead to reduced growth in the fish due to resultant intraperitoneal adhesions. Additionally, protocols incorporating booster doses via intraperitoneal injection demonstrated efficacy regardless of the administration route of the primary vaccination. Nevertheless, the use of booster vaccinations via the intraperitoneal route did not confer any significant advantage over a single intraperitoneal injection in terms of efficacy.

Safety and immunogenicity of the intranasal H3N2 M2-deficient single-replication influenza vaccine alone or coadministered with an inactivated influenza vaccine (Fluzone High-Dose Quadrivalent) in adults aged 65–85 years in the USA: a multicentre, randomised, double-blind, double-dummy, phase 1b trial

Older adults (aged ≥65 years) show increased susceptibility to severe disease with influenza virus infection, accounting for 70-85% of annual influenza-related fatalities in the USA. Stimulating mucosal antibodies and T cells might enhance the low vaccine effectiveness seen in older adults for currently licensed inactivated influenza vaccines, which induce mainly serum antibodies. We aimed to evaluate the safety and immunogenicity of the intranasal H3N2 M2-deficient single-replication (M2SR) vaccine, alone or coadministered with a licensed inactivated influenza vaccine (Fluzone High-Dose Quadrivalent; hereafter referred to as Fluzone HD), in older adults. In this multicentre, randomised, double-blind, double-dummy, phase 1b trial, individuals aged 65-85 years who were considered healthy or with stable chronic conditions with no recent (<6 months) influenza vaccinations were recruited from five clinical trial sites in the USA and randomly assigned (3:3:3:1) using a permuted block design to receive the H3N2 M2SR vaccine and Fluzone HD, the H3N2 M2SR vaccine and placebo, Fluzone HD and placebo, or placebo alone. All participants received a single intranasal spray and a single intramuscular injection, whether active or placebo, to maintain masking. The primary outcome was to assess the safety of H3N2 M2SR, administered alone or with Fluzone HD, in the safety analysis set, which included all participants who were randomly assigned and received treatment. Serum and mucosal antibodies were assessed as a secondary endpoint, and cell-mediated immunity as an exploratory endpoint, in participants in the per-protocol population, which included individuals in the safety analysis set without major protocol deviations. This trial is registered with ClinicalTrials.gov, NCT05163847. Between June 14 and Sept 15, 2022, 305 participants were enrolled and randomly assigned to receive the H3N2 M2SR vaccine plus placebo (n=89), H3N2 M2SR vaccine plus Fluzone HD (n=94), Fluzone HD plus placebo (n=92), or placebo alone (n=30). All randomly assigned participants were included in the safety analysis set. The most frequently reported local symptoms up to day 8 in groups that received M2SR were rhinorrhoea (43% [38 of 89] in the H3N2 M2SR plus placebo group and 38% [36 of 94] in the H3N2 M2SR plus Fluzone HD group), nasal congestion (51% [45 of 89] and 35% [33 of 94]), and injection-site pain (8% [seven of 89] and 49% [46 of 94]), and the most frequently reported solicited systemic symptoms were sore throat (28% [25 of 89]) for M2SR and decreased activity (26% [24 of 94]) for the M2SR plus Fluzone HD group. In the Fluzone HD plus placebo group, the most frequently reported local symptom was injection-site pain (48% [44 of 92]) and systemic symptom was muscle aches (22% [20 of 92]). The frequency of participants with any treatment-emergent adverse event related to vaccination was low across all groups (2-5%). One serious adverse event was reported, in a participant in the Fluzone HD plus placebo group. M2SR with Fluzone HD induced seroconversion (≥four-fold increase in haemagglutination inhibition antibodies from baseline to day 29) in 44 (48%) of 91 participants, compared with 28 (31%) of 90 participants who seroconverted in the Fluzone HD plus placebo group (p=0·023). M2SR with Fluzone HD also induced mucosal and cellular immune responses. The H3N2 M2SR vaccine coadministered with Fluzone HD in older adults was well tolerated and provided enhanced immunogenicity compared with Fluzone HD administered alone, suggesting potential for improved efficacy of influenza vaccination in this age group. Additional studies are planned to assess efficacy. US Department of Defense.

Structural insights into immune escape at killer T cell epitope by SARS-CoV-2 Spike Y453F variants

CD8+ T cell immunity, mediated by human leukocyte antigen (HLA) and T cell receptor (TCR), plays a critical role in conferring immune memory and protection against viral pathogens. The emergence of SARS-CoV-2 variants poses a serious challenge to the efficacy of current vaccines. Whereas numerous SARS-CoV-2 mutations associated with immune escape from CD8+ T cells have been documented, the molecular effects of most mutations on epitope-specific TCR recognition remain largely unexplored. Here, we studied an HLA-A24-restricted NYN epitope (Spike448-456) that elicits broad CD8+ T cell responses in COVID-19 patients characterized by a common TCR repertoire. Four natural mutations, N450K, L452Q, L452R, and Y453F, arose within the NYN epitope and have transmitted in certain viral lineages. Our findings indicate that these mutations have minimal impact on the epitope's presentation by cell surface HLA, yet they diminish the affinities of their respective peptide-HLA complexes (pHLAs) for NYN peptide-specific TCRs, particularly L452R and Y453F. Furthermore, we determined the crystal structure of HLA-A24 loaded with the Y453F peptide (NYNYLFRLF), and subsequently a ternary structure of the public TCRNYN-I complexed to the original NYN-HLA-A24 (NYNYLYRLF). Our structural analysis unveiled that despite competent presentation by HLA, the mutant Y453F peptide failed to establish a stable TCR-pHLA ternary complex due to reduced peptide: TCR contacts. This study supports the idea that cellular immunity restriction is an important driving force behind viral evolution.

Natural carriage of Streptococcus pneumoniae is associated with increased experimental pneumococcal carriage but reduced conjugate vaccine efficacy in a human challenge model.

In Malawi, the national pneumococcal conjugate vaccine (PCV13) demonstrated less herd immunity than the USA, likely due to higher natural pneumococcal carriage rates. We assessed PCV13 efficacy against experimental pneumococcal carriage in healthy Malawian adults. We explored how natural carriage (pneumococcal carriage of any other serotype apart from 6B) influenced experimental carriage rates and vaccine efficacy. Healthy adults aged 18-40 were randomly assigned PCV13 (n=98) or saline (n=106), followed by intranasal SPN 6B inoculation at 20,000 (n=40), 80,000 (n=74), or 160,000 (n=90) CFU/100µl, 28 days post-vaccination. We evaluated natural and experimental pneumococcal carriage before and after vaccination on days 2, 7, and 14 post-inoculation using culture and multiplex qPCR targeting lytA/cpsA genes and compared carriage rates by vaccination status. Of 204 participants, 19.6% (40) exhibited experimental carriage, detected by culture and 25.5% (52) by qPCR. Vaccinated individuals had lower experimental carriage rates (10.2%, n=10/98) compared to the placebo group (28.3%, n=30/106). This difference in vaccine efficacy was more pronounced in participants without natural carriage (PCV13=8% n=6/75 vs. placebo=25.9%, n=21/81) compared to those with natural carriage (PCV13=14.8%, n=4/27 vs. placebo=26.5%, n=9/34). Using a log-binomial model, vaccine effectiveness (VE) was 62%, whether assessed by culture or qPCR. Natural carriers had a lower VE of 52% compared to participants with no natural carriage (VE=69%). We have shown that PCV13 VE estimate (62%) is robust whether carriage is assessed by culture or qPCR. PCV13 had lower VE in natural carriers compared to those without natural carriage at the inoculation visit.

Vaccine enhancement and improved immunogenicity using erythrocytes as carriers

Achieving optimal immunogenicity and efficacy in vaccination presents significant challenges, including the need for multiple doses and the limited immunogenicity observed with certain vaccine formulations. To overcome these obstacles, researchers are exploring supplementary components and innovative delivery strategies. The development of an effective vaccine delivery technology is crucial for achieving sufficient protective immunity and disease prevention. This article focuses on the potential of erythrocytes as vaccine carriers to enhance vaccine effectiveness, particularly in the context of whole particle vaccines. The extended lifespan of erythrocytes enables sustained antigen exposure, resulting in continuous antigen presentation to immune cells. Moreover, erythrocytes exhibit biocompatibility, a well-established safety profile, and the capacity to modulate immune responses through interactions with complement receptors. These characteristics position erythrocytes as an appealing platform for targeted vaccine delivery. The hypothesis suggests utilizing bispecific monoclonal antibodies to complement receptor 1 and specific pathogen proteins to hitchhike inactivated pathogens onto erythrocytes. These modified erythrocytes can then serve as carriers to deliver the whole particle vaccine to antigen-presenting cells (APCs) or function as APCs themselves in the spleen. This article puts forward treatment protocols aimed at improving accessibility of vaccinations at the appropriate location, reducing the frequency of vaccine doses, and stimulating sufficient protective immunity.

Genetic and Pathogenic Analysis of a Novel Porcine Epidemic Diarrhea Virus Strain Isolated in the Republic of Korea

Porcine epidemic diarrhea (PED), caused by the porcine epidemic diarrhea virus (PEDV), emerges annually in several Asian countries. Its major symptoms include watery diarrhea, vomiting, anorexia, and dehydration. PED outbreaks incur significant economic losses. The efficacy of vaccines is limited by viral mutations and insufficient intestinal mucosal immunity. Therefore, new vaccines against these recent variants are urgently needed. Herein, we isolated and genetically characterized a novel Korean PEDV strain using NGS. Comparative genomic analysis demonstrated that the CKK1-1 strain belonged to genogroup 2. The isolated strain was cultured in sodium-glycochenodeoxycholic acid for 180 passages. Typically, PEDV isolation and passage require proteases, such as trypsin. However, the CKK1-1 strain adapted to this atypical culture condition, achieving a high titer of 8.83 ± 0.14 log TCID50/mL. In vitro biological analysis revealed no cell syncytium formation without trypsin; however, a cell-lysis-type cytopathic effect was noted. Notably, pathogenicity evaluation showed that CKK1-1 p0 exhibited naturally weakened virulence in five-day-old piglets, while piglets administered with CKK1-1 p180 exhibited 100% survival and reduced clinical symptoms. Collectively, our data demonstrate that this Korean PEDV strain, attenuated through atypical culture conditions with Na-glycochenodeoxycholic acid, has potential as a vaccine candidate, providing valuable insights into the genetic variation in and pathogenicity of PEDV.

Comparative Studies of Nairobi-Sheep-Disease Virus Strains Infectivity, Immunogenicty and Cross- Protectivity in BALB/C Mice Model

Nairobi sheep disease virus is a hemorrhagic virus that cause severe gastroenteritis in shoats resulting to significant morbidity and mortality in naïve small ruminants’ populations. Vaccine platform to develop efficacious vaccine against the Nairobi sheep disease virus have been unsuccessful. This research detail the comparative infection, immunogenicity, and protection of three Nairobi sheep strains; I34, 1473 and Ansell. The three strains are marked with differences in their ability to cause disease in suckling mice model. Fatality rates range from 0-50% from the virulent pathogenic 1473 strain, I34 and the seemingly less virulent Ansell strain also shown by their relative time to death. Findings of this research demonstrate that protective efficacy mediated by inactivated Nairobi sheep disease virus strain I34 conferred a stronger cross protection against homologous and heterologous strains compared to 1473 and Ansell strains. Strain I34 sera neutralization against homologous I34 strain was similar to that against Entebe strain providing evidence of possible antigenic homology. Vaccine developed from I34 strain will protect against multiple strains of Nairobi sheep disease virus; 1473, Ansell and Entebe strain. Understanding immune response in mice elicited by different Nairobi sheep disease virus strains will facilitate development of a more efficacious vaccine. Using formalin inactivated NSDV vaccine, I34 strain showed complete protection from homologous and a partial protection heterologous strains in in vitro assay. Protection was associated by higher neutralizing antibodies against homologous and heterologous strains compared to that of 1473 and Ansell. Thus, this study deduce serum neutralizing antibody titers are associated with protection against homologous and heterologous challenge

COVID-19 Vaccine in Lung and Liver Transplant Recipients Exceeds Expectations: An Italian Real-Life Experience on Immunogenicity and Clinical Efficacy of BNT162b2 Vaccine

This study assessed humoral and T cell-mediated immune responses to the BNT162b2 vaccine in orthotopic liver transplant (OLT) and lung transplant (LUT) recipients who received three doses of the vaccine from March 2021 at our institution. Serum samples were collected 60 days post-second and third dose to quantify antibodies against the spike region of SARS-CoV-2 while whole blood samples were collected to analyze the SARS-CoV-2-specific T-cell response using an IFN-γ ELISpot assay. We enrolled 244 OLT and 120 LUT recipients. The third dose increased antibody titres in OLT recipients (from a median value of 131 after the second dose to 5523 IU/mL, p &amp;lt; 0.001) and LUT recipients (from 14.8 to 1729 IU/mL, p &amp;lt; 0.001). T-cell response also increased in OLT recipients (from 8.5 to 23 IFN-γ SFU per 250,000 PBMC, p &amp;lt; 0.001) and LUT recipients (from 8 to 15 IFN-γ SFU per 250,000 PBMC, p &amp;lt; 0.001). A total of 128 breakthrough infections were observed: two (0.8%) OLT recipients were hospitalized due to COVID-19 and one died (0.4%); among LUT recipients, seven were hospitalized (5.8%) and two patients died (1.7%). In conclusion, the three-dose schedule of the BNT162b2 vaccine elicited both humoral and T cell-mediated responses in solid organ transplant recipients. The risk of severe COVID-19 post-vaccination was low in this population.

Evaluation of Infectivity and Immunogenicity of Sugar Stabilized Nairobi Sheep Disease Vaccine

This work presents a cost-effective approach that can tremendously reduce the financial and logistical burden for vaccine delivery. Strict requirement of a cold chain account about 80% of the total cost of vaccination program. This research paper detail the use of inexpensive FDA approved biocompatible sugars for stabilizing inactivated Nairobi sheep disease virus vaccine. We evaluated sugar additives that improve the storage and maintain the antigenic properties of inactivated vaccine. Low concentrations of trehalose and sucrose maintain the residual infectivity of the virus. Nairobi sheep disease virus vaccine was lyophilized in trehalose and sucrose and subjected to accelerated stability test at temperatures; 25 0C, 37 0C and 40 0C. Results of this study showed the sugar stabilizers can retain residual infectivity for 14 days at 400C. Stabilization effect of trehalose and sucrose preserve the efficacy of inactivated vaccine stored at 40 0C for despite loss of infectivity.

Dysregulated cytokine and oxidative response in hyper-glycolytic monocytes in obesity

IntroductionObesity is associated with a plethora of health complications, including increased susceptibility to infections or decreased vaccine efficacy, partly due to dysregulated immune responses. Monocytes play a crucial role in innate immunity, yet their functional alterations in obesity remain poorly understood.MethodsHere, we employed proteomic and metabolomic analyses to investigate monocyte characteristics in individuals with overweight, obesity, impaired glucose tolerance (IGT), and type 2 diabetes (T2D), compared to lean donors.Results and discussionOur results revealed distinct molecular signatures in monocytes from individuals with obesity, with significant alterations in pathways related to metabolism, cellular migration, and phagocytosis. Moreover, LPS-induced activation of monocytes unveiled heightened metabolic reprogramming towards glycolysis in subjects with obesity accompanied by dysregulated cytokine responses and elevated oxidative stress. Additionally, monocytes from donors with obesity exhibited increased lipid droplet accumulation. These findings shed light on the immunometabolic dysregulation underlying obesity-associated immune dysfunction, highlighting potential targets for therapeutic intervention.

Immunogenicity and vaccine potential of clinical isolate Mycobacterium kansasii strain against Mycobacterium tuberculosis infection.

Mycobacterium kansasii is a bacterium included in non-tuberculous mycobacteria (NTM) that can cause lung disease. It shares a significant number of antigens with Mycobacterium tuberculosis (Mtb), suggesting that it has the potential to be used as a tuberculosis (TB) vaccine. Therefore, we subcutaneously vaccinated mice with reference strain, M. kansasii-ATCC12478 [M. kansasii-American Type Culture Collection (ATCC)], and clinically isolated strain, M. kansasii-SM-1 to evaluate potential as a TB vaccine by comparing with bacille Calmette-Guerin (BCG) vaccine. Ten weeks after vaccination, we evaluated immunogenicity of M. kansasii-ATCC and M. kansasii-SM-1, and M. kansasii-SM-1 immunization induces potent Mtb antigen-specific IFN-γ-producing CD4+ T cells than M. kansasii-ATCC. Upon Mtb infection, M. kansasii-SM-1 provided better protection than M. kansasii-ATCC, which was comparable to the efficacy of BCG. These results showed that the clinical strain M. kansasii-SM-1, which exhibits an enhanced Mtb antigen-specific Th1 response, shows greater vaccine efficacy compared to M. kansasii-ATCC. In this study, we demonstrated that vaccine efficacy can vary depending on the strain of M. kansasii and that its efficacy can be comparable to BCG. This suggests that M. kansasii has the potential to be a live TB vaccine candidate.IMPORTANCEMycobacterium kansasii, a non-tuberculous mycobacteria (NTM) species causing lung disease, shares key antigens with Mycobacterium tuberculosis (Mtb), indicating its potential for TB vaccine development. Subcutaneous vaccination of mice with M. kansasii strains reference strain M. kansasii-ATCC12478 [(M. kansasii-American Type Culture Collection (ATCC)] and clinically isolated strain M. kansasii-SM-1 revealed differences in immunogenicity. M. kansasii-SM-1 induced a robust Mtb antigen-specific IFN-γ-producing CD4+ T cell response compared to M. kansasii-ATCC. Additionally, M. kansasii-SM-1 conferred better protection against Mtb infection than M. kansasii-ATCC, which is comparable to bacille Calmette-Guerin (BCG). These findings underscore the variable vaccine efficacy among M. kansasii strains, with M. kansasii-SM-1 exhibiting promising potential as a live TB vaccine candidate, suggesting its comparative effectiveness to BCG.

Social Media Authentication and Users' Assessments of Health Information: Random Assignment Survey Experiment.

In an effort to signal the authenticity of user accounts, social networking sites (SNSs) such as Facebook and X, formerly known as Twitter, use visual heuristics (blue checkmarks) to signify whether accounts are verified. While these verification badges are generally well recognized (and often coveted) by SNS users, relatively little is known about how they affect users' perceptions of accuracy or their likelihood of engaging with web-based information. This is particularly true in the case of information posted by medical experts and health care professionals. This study aims to use an experimental survey design to assess the effect of these verification badges on SNS users' assessments of information accuracy as well as their proclivity to recirculate health information or follow verified medical experts in their social network. A survey experiment using random assignment was conducted on a representative sample of 534 adult SNS users in Florida, United States. A total of 2 separate experimental scenarios exposed users to vaccine-related posts from verified medical experts on X. In each case, the original post contained a platform-issued verification badge (treatment group), which was subsequently edited out of the image as an experimental control. For each scenario, respondents were randomly assigned to either the treatment or control group, and responses to 3 follow-up questions were assessed through a series of chi-square analyses and 2 logit regression models. Responses were fielded using a stratified quota sampling approach to ensure representativeness of the state's population based on age, sex, race, ethnicity, and political affiliation. Users' assessments of information accuracy were not significantly impacted by the presence or absence of verification badges, and users exposed to the experimental treatment (verification badge) were not any more likely to repost the message or follow the author. While verification badges did not influence users' assessments or subsequent behaviors, reliance on social media for health-related information and political affiliation were substantial predictors of accuracy assessments in both experimental scenarios. In scenario 1, which included a post addressing COVID-19 vaccine efficacy, users who relied on social media "a great deal" for health information were 2 times more likely to assess the post as accurate (odds ratio 2.033, 95% CI 1.129-3.661; P=.01). In scenario 2, which included a post about measles vaccines, registered Republicans were nearly 6 times less likely to assess the post as accurate (odds ratio 0.171, 95% CI 0.097-0.299; P<.001). For health professionals and medical experts wishing to leverage social networks to combat misinformation and spread reliable health-related content, account verification appears to offer little by way of added value. On the basis of prior research, other heuristics and communication strategies are likely to yield better results.

Assessing the impacts of vaccination and viral evolution in contact networks

A key lesson learned with COVID-19 is that public health measures were very different from country to country. In this study, we provide an analysis of epidemic dynamics using three well-known stochastic network models—small-world networks (Watts–Strogatz), random networks (Erdös–Rényi), and scale-free networks (Barabási–Albert)—to assess the impact of different viral strains, lockdown strategies, and vaccination campaigns. We highlight the significant role of highly connected nodes in the spread of infections, particularly within Barabási–Albert networks. These networks experienced earlier and higher peaks in infection rates, but ultimately had the lowest total number of infections, indicating their rapid transmission dynamics. We also found that intermittent lockdown strategies, particularly those with 7-day intervals, effectively reduce the total number of infections, serving as viable alternatives to prolonged continuous lockdowns. When simulating vaccination campaigns, we observed a bimodal distribution leading to two distinct outcomes: pandemic contraction and pandemic expansion. For WS and ER networks, rapid mass vaccination campaigns significantly reduced infection rates compared to slower campaigns; however, for BA networks, differences between vaccination strategies were minimal. To account for the evolution of a virus into a more transmissible strain, we modeled vaccination scenarios that varied vaccine efficacy against the wild-type virus and noted a decline in this efficacy over time against a second variant. Our results showed that vaccination coverage above 40% significantly flattened infection peaks for the wild-type virus, while at least 80% coverage was required to similarly reduce peaks for variant 2. Furthermore, the effect of vaccine efficacy on reducing the peak of variant 2 infection was minimal. Although vaccination strategies targeting hub nodes in scale-free networks did not substantially reduce the total number of infections, they were effective in increasing the probability of preventing pandemic outbreaks. These findings underscore the need to consider the network structure for effective pandemic control.

Assessment of Antibody Titers after 6 Months of Vaccination against SARS-COV-2 in Patients with CKD Stage 4, 5 and CKD 5d

Background: Since the pandemic of COVID-19 started from December 2019, remarkable numbers of infections and deaths associated with COVID-19 have been recorded worldwide. Chronic kidney disease patients are particularly at high risk of infections due to impairments in the innate and adaptive immune systems. Adequate humoral (antibody) and cellular (T cell-driven) immunity are required to minimize pathogen entry and promote pathogen clearance to enable infection control. Vaccination can generate cellular and humoral immunity against this specific pathogen. COVID-19 prevention through successful vaccination is therefore paramount in chronic kidney disease population. But vaccination efficacy is diminished in these patients because premature ageing of the immune system and chronic systemic low- grade inflammation are the main causes of immune alteration in these patients. Therefore, it is urgently necessary to establish a different vaccination strategy for chronic kidney disease and dialysis patient in terms of the dose and administration time. Aims: This study aimed to assessment of antibody titers after vaccination against SARS-COV-2 in patients with chronic kidney disease stage 4, 5 on conservative management and maintenance haemodialysis. Methods: This prospective observational comparative was conducted in Nephrology department of Dhaka Medical College Hospital. Selectionof patients was done by purposive sampling according to inclusion and exclusion criteria. Total 135 patients distributed in three groups: 45 patients of chronic kidney disease (CKD) stage 4, 5 on conservative management, 45 patients on maintenance haemodialysis (MHD) and 45 healthy controls were approached for the study who were receiving SARS-COV-2 vaccination. Demographic, clinical and laboratory data were collected initially. At first a pre vaccination sample or 1st sample was taken for antibody measurement. Then participants from all groups were given 2 doses MODERNA vaccine containing 100 µg in 0.5 ml each in 28 days apart. Then after 14 days of 1st dose of vaccination the 2nd samples were taken, 3rd samples were taken 14 days after the 2nd dose vaccination. Study populations were subdivided into two groups according to pre vaccination SARS-COV-2 antibody titer; seropositive- positive response before vaccination and seronegative- negative response before vaccination. They were also divided into two groups according to quantitive antibody response; positive response- values ≥10 DU/mL were positive Negative response- values of &lt;10 DU/mL were negative. Result: Seroconversion rate was around 20% among study participants before vaccination. 14 days after the 1st dose of vaccination, 90.04% patients had positive immune response in CKD stage 4, 5 on conservative management group whereas in MHD group 84.82% responded to vaccination and immune response in control group was 100%. Immune response is 100% among all the groups after 14 days of 2nd dose of vaccination but the concentration of antibody differs significantly among the study groups. Responders were comparatively younger with normal BMI. Conclusion: Haemodialysis patients as well as patients with chronic kidney disease stage 4, 5 on conservative management showed a favorable but profoundly lower early antibody response, which decreased substantially during follow-up.

Protection against experimental cryptococcosis elicited by Cationic Adjuvant Formulation 01-adjuvanted subunit vaccines.

The fungal infection, cryptococcosis, is responsible for >100,000 deaths annually. No licensed vaccines are available. We explored the efficacy and immune responses of subunit cryptococcal vaccines adjuvanted with Cationic Adjuvant Formulation 01 (CAF01). CAF01 promotes humoral and T helper (Th) 1 and Th17 immune responses and has been safely used in human vaccine trials. Four subcutaneous vaccines, each containing single recombinant Cryptococcus neoformans protein antigens, partially protected mice from experimental cryptococcosis. Protection increased, up to 100%, in mice that received bivalent and quadrivalent vaccine formulations. Vaccinated mice that received a pulmonary challenge with C. neoformans had an influx of leukocytes into the lung including robust numbers of polyfunctional CD4+ T cells which produced Interferon gamma (IFNγ), tumor necrosis factor alpha (TNFα), and interleukin (IL)-17 upon ex vivo antigenic stimulation. Cytokine-producing lung CD8+ T cells were also found, albeit in lesser numbers. A significant, durable IFNγ response was observed in the lungs, spleen, and blood. Moreover, IFNγ secretion following ex vivo stimulation directly correlated with fungal control in the lungs. Thus, we have developed multivalent cryptococcal vaccines which protect mice from experimental cryptococcosis using an adjuvant which has been safely tested in humans. These preclinical studies suggest a path towards human cryptococcal vaccine trials.

A Flagellin-Adjuvanted Trivalent Mucosal Vaccine Targeting Key Periodontopathic Bacteria

Periodontal disease (PD) is caused by microbial dysbiosis and accompanying adverse inflammatory responses. Due to its high incidence and association with various systemic diseases, disease-modifying treatments that modulate dysbiosis serve as promising therapeutic approaches. In this study, to simulate the pathophysiological situation, we established a “temporary ligature plus oral infection model” that incorporates a temporary silk ligature and oral infection with a cocktail of live Tannerella forsythia (Tf), Pophyromonas gingivalis (Pg), and Fusobacterium nucleatum (Fn) in mice and tested the efficacy of a new trivalent mucosal vaccine. It has been reported that Tf, a red complex pathogen, amplifies periodontitis severity by interacting with periodontopathic bacteria such as Pg and Fn. Here, we developed a recombinant mucosal vaccine targeting a surface-associated protein, BspA, of Tf by genetically combining truncated BspA with built-in adjuvant flagellin (FlaB). To simultaneously induce Tf-, Pg-, and Fn-specific immune responses, it was formulated as a trivalent mucosal vaccine containing Tf-FlaB-tBspA (BtB), Pg-Hgp44-FlaB (HB), and Fn-FlaB-tFomA (BtA). Intranasal immunization with the trivalent mucosal vaccine (BtB + HB + BtA) prevented alveolar bone loss and gingival proinflammatory cytokine production. Vaccinated mice exhibited significant induction of Tf-tBspA-, Pg-Hgp44-, and Fn-tFomA-specific IgG and IgA responses in the serum and saliva, respectively. The anti-sera and anti-saliva efficiently inhibited epithelial cell invasion by Tf and Pg and interfered with biofilm formation by Fn. The flagellin-adjuvanted trivalent mucosal vaccine offers a novel method for modulating dysbiotic bacteria associated with periodontitis. This approach leverages the adjuvant properties of flagellin to enhance the immune response, aiming to restore a balanced microbial environment and improve periodontal health.

Protection against experimental cryptococcosis elicited by Cationic Adjuvant Formulation 01-adjuvanted subunit vaccines.

The fungal infection, cryptococcosis, is responsible for >100,000 deaths annually. No licensed vaccines are available. We explored the efficacy and immune responses of subunit cryptococcal vaccines adjuvanted with Cationic Adjuvant Formulation 01 (CAF01). CAF01 promotes humoral and T helper (Th) 1 and Th17 immune responses and has been safely used in human vaccine trials. Four subcutaneous vaccines, each containing single recombinant Cryptococcus neoformans protein antigens, partially protected mice from experimental cryptococcosis. Protection increased, up to 100%, in mice that received bivalent and quadrivalent vaccine formulations. Vaccinated mice that received a pulmonary challenge with C. neoformans had an influx of leukocytes into the lung including robust numbers of polyfunctional CD4+ T cells which produced Interferon gamma (IFNγ), tumor necrosis factor alpha (TNFα), and interleukin (IL)-17 upon ex vivo antigenic stimulation. Cytokine-producing lung CD8+ T cells were also found, albeit in lesser numbers. A significant, durable IFNγ response was observed in the lungs, spleen, and blood. Moreover, IFNγ secretion following ex vivo stimulation directly correlated with fungal control in the lungs. Thus, we have developed multivalent cryptococcal vaccines which protect mice from experimental cryptococcosis using an adjuvant which has been safely tested in humans. These preclinical studies suggest a path towards human cryptococcal vaccine trials.

Impact of COVID-19 Vaccine Persuasion Strategies on Social Endorsement and Public Response on Chinese Social Media

ABSTRACT Persuading the public to get vaccinated against infectious diseases is critical and carries profound implications for preparing for future pandemics. This study examined whether and how persuasion strategies employed in pro-vaccine messages affect social endorsement and audience stance toward the COVID-19 vaccine expressed in comments on Chinese social media. Through manual coding and pre-trained BERT model, we analyzed 1,500 Weibo posts focused on COVID-19 vaccination persuasion and 238,201 associated comments. Results showed that medical experts succeeded in eliciting heightened social endorsement and receiving more pro-vaccine comments. Posts that employed negative emotional appeal were less likely to be liked or receive pro-vaccine comments. Besides, vaccine persuasion messages presented in a narrative format or emphasizing vaccine efficacy garnered significantly more likes but did not significantly receive more pro-vaccine comments. Discussing domestic issues or employing joy appeal received more pro-vaccine comments. These results offer valuable insights for health practitioners and communicators, highlighting more effective persuasion strategies for engaging citizens in vaccine-related discussions on social media. This study underscores the importance of leveraging persuasion tactics on social media to foster vaccination uptake and better prepare us for handling future pandemics.