Augmenting vaccine efficacy: Tailored immune strategy with alum-stabilized Pickering emulsion.

BACKGROUND: The achievement of optimal vaccine efficacy is contingent upon the collaborative interactions between T and B cells in adaptive immunity. Although multiple immunization strategies have been proposed, there is a notable scarcity of comprehensive investigations pertaining to enhance immune effects through immune strategy adjustments for individual vaccine. METHODS: The hierarchically structured aluminum hydroxide microgel-stabilized Pickering emulsion (ASPE) was prepared by ultrasonic method. This study explored the influence of the immune strategy of ASPE to immune responses, including antigen exposure pattern, adjuvants and antigen dosage, and administration interval. RESULTS: The findings revealed that external antigen adsorption facilitated increased exposure of antigen epitopes, leading to elevated IgG titers and secretion of cytokines such as interferon-gamma (IFN-γ) or interleukin-4 (IL-4). Additionally, even a low dose (1 µg/dose) of antigens of ASPE boosted sufficient neutralizing antibody levels and memory T cells compared to high-dose antigens, which consistent with the adjuvant dosage effect. Furthermore, maintaining a 4-week immunization interval yielded optimal levels of antigen-specific IgG titers in both short-term and long-term scenarios, as compared to intervals of 2, 3, and 5 weeks. A consistent trend was observed in the proliferation of memory B cells, reaching a superior level at the 4-week interval, which could enhance protection against viral re-infection. CONCLUSION: Tailoring immunization strategies for specific vaccines has emerged as powerful driver in maximizing vaccine efficacy and eliciting robust immune responses, thereby presenting cutting-edge approaches to enhanced vaccination.

Could care giving have altered the evolution of human immune strategies?

Life history theory indicates that individuals/species with a slow pace of life invest more in acquired than innate immunity. Factors that decrease the pace of life and predict greater investment in acquired immunity include increased nutritional resources, increased pathogen exposure and decreased risk of extrinsic mortality. Common care behaviors given to sick individuals produce exactly these effects: provisioning increases nutritional resources; hygiene assistance increases disease exposure of carers; and protection can reduce the risk of extrinsic mortality to sick individuals. This study, therefore, investigated under what conditions care giving behaviors might impact immune strategy and pace of life. The study employed an agent-based model approach that simulated populations with varying levels of care giving, disease mortality, disease transmissibility, and extrinsic mortality, enabling measurements of how the immune strategy and age structure of the populations changed over evolutionary time. We used multiple regressions to examine the effects of these variables on immune strategy and the age structure of the population. The findings supported our predictions that care was selected for an acquired immunity. However, the pace of life did not slow as expected. Instead, the population shifted to a faster, but also more cost-intensive reproductive strategy in which care improved child survival by subsidizing the development of acquired immune responses.

Shifts in immune responses of an invasive alien species: A test of the evolution of increased competitive ability hypothesis using American Eastern gray squirrels in Italy.

Based on the Evolution of Increased Competitive Ability (EICA) hypothesis, a reduced investment in immunity, consequent to parasite loss, could partly explain the success of invasive alien species. We investigated variation in parasite load and immune responses of alien Eastern gray squirrels (Sciurus carolinensis) along the invasion wave of an expanding population. We first verified by fecal analyses that 1) parasite abundance decreased moving from the core towards the invasion front. Next, we used multiple measures of immunity to investigate whether, in response to the lower parasite pressure, individuals at the invasion front 2) dampened their costly inflammatory response, and 3) increased their investment in less expensive acquired immunity. We first explored variation in hematological variables related either to the inflammatory or the acquired response. On a subset of individuals, we carried out ex vivo cell cultures to analyse the basal expression of MHC class II genes and the expression of TNF-α genes in response to an immune challenge. Platelet counts and TNF-α expression suggested higher inflammation in individuals living at the invasion core, whereas parameters associated with an acquired response (lymphocyte counts and MHC II expression by spleen cells), conversely, were higher in squirrels at the front. Overall, our results suggest a shift between different immune strategies along the invasion wave, supporting a reduced investment in costly inflammatory responses and an increased investment in acquired immunity in individuals at the expanding edge of the range, which are subjected to high selective pressures for dispersal and reproduction.

Changes in the immune function of rainbow trout (Oncorhynchus mykiss) provide insights into strategies against BDE-47 stress.

Polybrominated diphenyl ethers (PBDEs) are ubiquitous in marine ecosystems and have been suggested to bioaccumulate in aquatic food webs, with potentially negative impacts on marine organism. In this study, a 21-day experiment was performed under controlled laboratory conditions, in which 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), the most biotoxic PBDE in the marine environment, was fed to rainbow trout (Oncorhynchus mykiss) at concentrations of 50 and 500 ng g-1 in the diet. BDE-47 significantly decreased the specific growth rate of O. mykiss and was highly concentrated in the liver and head kidney, as evidenced by increased bioaccumulation factor (BAF) values. Tissue observation revealed impairment of the microstructure of the head kidney. Important immune factors in the skin, blood and head kidney were significantly inhibited by BDE-47 treatment (p < 0.05), whereas the respiratory burst activity of macrophages was enhanced. Additionally, immune-related genes were strongly downregulated following BDE-47 exposure (p < 0.05). In a bacterial challenge, the treatment groups had much higher mortality than did the control group (p < 0.05). BDE-47 accumulated and impaired immune organs, and the hierarchy of immune responses was impaired, consequently reducing O. mykiss resistance to pathogen invasion.

Parasite Load and Site-Specific Parasite Pressure as Determinants of Immune Indices in Two Sympatric Rodent Species.

Wildlife is exposed to parasites from the environment. This parasite pressure, which differs among areas, likely shapes the immunological strategies of animals. Individuals differ in the number of parasites they encounter and host, and this parasite load also influences the immune system. The relative impact of parasite pressure vs. parasite load on different host species, particularly those implicated as important reservoirs of zoonotic pathogens, is poorly understood. We captured bank voles (Myodes glareolus) and wood mice (Apodemus sylvaticus) at four sites in the Netherlands. We sampled sub-adult males to quantify their immune function, infestation load for ecto- and gastrointestinal parasites, and infection status for vector-borne microparasites. We then used regression trees to test if variation in immune indices could be explained by among-site differences (parasite pressure), among-individual differences in infestation intensity and infection status (parasite load), or other intrinsic factors. Regression trees revealed splits among sites for haptoglobin, hemagglutination, and body-mass corrected spleen size. We also found splits based on infection/infestation for haptoglobin, hemolysis, and neutrophil to lymphocyte ratio. Furthermore, we found a split between species for hemolysis and splits based on body mass for haptoglobin, hemagglutination, hematocrit, and body-mass corrected spleen size. Our results suggest that both parasite pressure and parasite load influence the immune system of wild rodents. Additional studies linking disease ecology and ecological immunology are needed to understand better the complexities of host-parasite interactions and how these interactions shape zoonotic disease risk.

[Cost-effectiveness analysis of rabies immunization strategy based on dynamic-decision tree model].

Objective: To evaluate the cost-utility of different immunization strategies for rabies in China, and to provide a reference for determining the optimal immunization strategy. Methods: The system dynamics model was used to simulate the epidemic of canine rabies and a decision tree model was conducted to analysis different immune strategies. Relevant probabilities were obtained through literature search and on-site investigation. Sensitivity analysis was used to explore the important influenced factors. Results: At baseline, from a social perspective, 70% vaccination of dogs was the optimal strategy compared to current vaccination strategy (43% vaccination in dogs, human category-Ⅱ exposure vaccination/category-Ⅲ exposure vaccination combined with RIG). The total cost was 14 084 354 CNY, and the total utility value was 22 078 616.23 QALYs, and the incremental cost-utility ratio was-62 148 147 CNY/QALY; if human vaccination was considered, 55% vaccination of dogs combined with strategy one was the optimal strategy, its incremental cost-utility ratio was-444 620 557 CNY/QALY. The probability that an injured dog carries rabies virus was the most sensitive parameter. When it was greater than 0.005 03, strategy four was the optimal strategy. When it was less than 82/100 000, strategy one was the optimal strategy; when it was between 82/100 000 and 120/100 000, strategy two was the optimal strategy; when it was between 120/100 000 and 503/100 000, strategy two was the optimal strategy. Conclusion: It was conducive to increase the vaccination coverage of canine for the prevention and control of rabies.

Cost-effectiveness analysis of rabies immunization strategy based on dynamic-decision tree model / 中华预防医学杂志

Objective@#To evaluate the cost-utility of different immunization strategies for rabies in China, and to provide a reference for determining the optimal immunization strategy.@*Methods@#The system dynamics model was used to simulate the epidemic of canine rabies and a decision tree model was conducted to analysis different immune strategies. Relevant probabilities were obtained through literature search and on-site investigation. Sensitivity analysis was used to explore the important influenced factors.@*Results@#At baseline, from a social perspective, 70% vaccination of dogs was the optimal strategy compared to current vaccination strategy (43% vaccination in dogs, human category-Ⅱ exposure vaccination/category-Ⅲ exposure vaccination combined with RIG). The total cost was 14 084 354 CNY, and the total utility value was 22 078 616.23 QALYs, and the incremental cost-utility ratio was-62 148 147 CNY/QALY; if human vaccination was considered, 55% vaccination of dogs combined with strategy one was the optimal strategy, its incremental cost-utility ratio was-444 620 557 CNY/QALY. The probability that an injured dog carries rabies virus was the most sensitive parameter. When it was greater than 0.005 03, strategy four was the optimal strategy. When it was less than 82/100 000, strategy one was the optimal strategy; when it was between 82/100 000 and 120/100 000, strategy two was the optimal strategy; when it was between 120/100 000 and 503/100 000, strategy two was the optimal strategy.@*Conclusion@#It was conducive to increase the vaccination coverage of canine for the prevention and control of rabies.

A candidate tolerance gene identified in a natural population of field voles (Microtus agrestis).

The animal immune response has hitherto been viewed primarily in the context of resistance only. However, individuals can also employ a tolerance strategy to maintain good health in the face of ongoing infection. To shed light on the genetic and physiological basis of tolerance, we use a natural population of field voles, Microtus agrestis, to search for an association between the expression of the transcription factor Gata3, previously identified as a marker of tolerance in this system, and polymorphism in 84 immune and nonimmune genes. Our results show clear evidence for an association between Gata3 expression and polymorphism in the Fcer1a gene, with the explanatory power of this polymorphism being comparable to that of other nongenetic variables previously identified as important predictors of Gata3 expression. We also uncover the possible mechanism behind this association using an existing protein-protein interaction network for the mouse model rodent, Mus musculus, which we validate using our own expression network for M. agrestis. Our results suggest that the polymorphism in question may be working at the transcriptional level, leading to changes in the expression of the Th2-related genes, Tyrosine-protein kinase BTK and Tyrosine-protein kinase TXK, and hence potentially altering the strength of the Th2 response, of which Gata3 is a mediator. We believe our work has implications for both treatment and control of infectious disease.

Evaluation of the effects of different vaccinations in muscles with DNA vaccine against Mycobacterium tuberculosis delivered by electroporation / 中华微生物学和免疫学杂志

Objective To evaluate the effects of different vaccinations in muscles with DNA vac-cine against Mycobacterium tuberculosis delivered by electroporation and to obtain an optimum immune strate-gy.Methods Forty female BALB/c mice were randomly divided into four groups and immunized intramus-cularly by electroporation with saline , 50 μg of Ag85A DNA, 100 μg of Ag85A DNA and mixed Ag85A DNA ( first time 10 μg of DNA, second time 100 μg of DNA and third time 10 μg of DNA) for three times with two weeks interval , respectively .At the second and sixth weeks after the final immunization , five mice from each group were sacrificed each time .The levels of IFN-γand IL-4 in supernatants of splenic lympho-cyte culture were measured by enzyme-linked immunosorbent assay (ELISA).The ratios of CD4+T cells ex-pressing IFN-γ( Th1) and IL-4 ( Th2) in whole blood samples were detected by flow cytometry .The copies of Ag85A DNA in the positions of intramuscular injection were measured by quantitative RT-PCR.The levels of specific IgG antibodies response to Ag85A in serum samples from mice before immunization (pre-immune serum samples ) and 10 days after each immunization were detected by ELISA .Results Two weeks after the final immunization , the IFN-γlevels in the supernatants of splenocyte culture from mice immunized with mixed Ag85A DNA [(703.66±394.74) pg/ml] and 50 μg of Ag85A DNA [(648.60±439.41) pg/ml] were significantly higher than those in saline treated group [(70.58±108.76) pg/ml, t=3.975 and 3.629, P=0.0004 and 0.0010] and 100μg of Ag85A DNA immunized group [(86.08±135.73) pg/ml, t=3.878 and 3.532, P=0.0005 and 0.0013].No differences with the levels of IFN-γwere observed between mixed Ag85A DNA immunized group and 50 μg of Ag85A DNA immunized group (t=0.3457, P=0.7318).The ratios of Th1/Th2 cells in whole blood samples react to Ag 85A protein from mice in mixed Ag85A DNA trea-ted group (3.82±1.09) were significantly higher than those in saline treated group (0.37±0.11), 50μg of Ag85A DNA treated group (1.20±0.80) and 100 μg of Ag85A DNA treated group (1.10±0.60) (t=2.980, 2.260 and 2.352, P=0.0058, 0.0315 and 0.0257).The copies of Ag85A DNA in intramuscular injection positions of mice from 100 μg of Ag85A DNA treated group [(963.40±892.79) copies] were sig-nificantly higher than those in 50 μg of Ag85A DNA treated group [(270.90±398.18) copies] and mixed Ag85A DNA treated group [(205.80±136.95) copies] (t=2.639 and 2.887, P=0.0144 and 0.0081). Six weeks after the final immunization , IFN-γlevels in the supernatants of splenocyte culture from mice im-munized with mixed Ag85A DNA [(238.43±258.90)pg/ml)] were higher than those in saline treated group [(0±0) pg/ml], 50 μg of DNA treated group [(83.14±135.08) pg/ml] and 100 μg Ag85A DNA treated group [(163.83 ±207.13) pg/ml], but there were no significant differences between them ( t=1.497, 0.9750 and 0.4684, P=0.1442, 0.3369 and 0.6427).The ratios of Th1/Th2 cells in whole blood samples react to Ag85A protein from mice immunized with mixed Ag85A DNA (4.67±5.05) were signifi-cantly higher than those immunized saline (0.77±0.19), 50μg of Ag85A DNA (1.23±0.74) and 100 μg of Ag85A DNA (0.51±0.49) (t=3.199, 2.971 and 3.610, P=0.0033, 0.0059 and 0.0011).The cop-ies of Ag85 A DNA in the positions of intramuscular injection showed no significant differences among all groups .Conclusion The results of this study suggested that lower doses of DNA immunization delivered by electroporation could improve immune responses and produce better immune effects .The optimum immune strategy was mixed immunization of DNA by electroporation .After the second immunization , the levels of specific IgG antibodies react to Ag85A protein in serum samples from mice immunized with 50 μg of Ag85A DNA , 100μg of Ag85A DNA and mixed Ag85A DNA were obviously increased than those of each group af-ter the first immunization (F=7.17,P=0.0111), but there was no significant difference between them .Ex-cept the 50 μg Ag85A DNA treated group, the levels of specific IgG antibodies response to Ag 85A in serum samples from mice immunized with 100 μg of Ag85A DNA and mixed Ag85A DNA were increased after the third immunization as compared with those of each group after the second immunization , but no significant difference was found between them .

Immune strategies using single-component LipL32 and multi-component recombinant LipL32-41-OmpL1 vaccines against leptospira

Genes encoding lipoproteins LipL32, LipL41 and the outer-membrane protein OmpL1 of leptospira were recombined and cloned into a pVAX1 plasmid. BALB/c mice were immunized with LipL32 and recombined LipL32-41-OmpL1 using DNA-DNA, DNA-protein and protein-protein strategies, respectively. Prime immunization was on day 1, boost immunizations were on day 11 and day 21. Sera were collected from each mouse on day 35 for antibody, cytokine detection and microscopic agglutination test while spleen cells were collected for splenocyte proliferation assay. All experimental groups (N = 10 mice per group) showed statistically significant increases in antigen-specific antibodies, in cytokines IL-4 and IL-10, as well as in the microscopic agglutination test and splenocyte proliferation compared with the pVAX1 control group. The groups receiving the recombined LipL32-41-OmpL1 vaccine induced anti-LipL41 and anti-OmpL1 antibodies and yielded better splenocyte proliferation values than the groups receiving LipL32. DNA prime and protein boost immune strategies stimulated more antibodies than a DNA-DNA immune strategy and yielded greater cytokine and splenocyte proliferation than a protein-protein immune strategy. It is clear from these results that recombination of protective antigen genes lipL32, lipL41, and ompL1 and a DNA-protein immune strategy resulted in better immune responses against leptospira than single-component, LipL32, or single DNA or protein immunization.