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Regulating tumor microenvironments by a lymph node-targeting adjuvant via tumor-specific CTL-derived IFNγ

Xu X, Yi C, Feng T, Ge Y, Liu M, Wu C, et al.

Clin Immunol, 2023 Aug;253:109685.
PMID: 37406980 DOI: 10.1016/j.clim.2023.109685

Inducing tumor-specific T cell responses and regulating suppressive tumor microenvironments have been a challenge for effective tumor therapy. CpG (ODN), the Toll-like receptor 9 agonist, has been widely used as adjuvants of cancer vaccines to induce T cell responses. We developed a novel adjuvant to improve the targeting of lymph nodes. CpG were modified with lipid and glycopolymers by the combination of photo-induced RAFT polymerization and click chemistry, and the novel adjuvant was termed as lipid-glycoadjuvant@AuNPs (LCpG). OVA protein was used as model antigen and melanoma model was established to test the immunotherapy effect of the adjuvant. In tumor model, the antitumor effect and mechanism of LCpG on the response of CTLs were examined by flow cytometry and cell cytotoxicity assay. The effects of LCpG on macrophage polarization and Tregs differentiation in tumor microenvironment were also studied by cell depletion assay and cytokine neutralization assay. We also tested the therapeutic effect of the combination of the adjuvant and anti-PD-1 treatment. LCpG could be rapidly transported to and retained longer in the lymphoid nodes than unmodified CpG. In melanoma model, LCpG controlled both primary tumor and its metastasis, and established long-term memory. In spleen and tumor draining lymphoid nodes, LCpG activated tumor-specific Tc1 responses, with increased CD8+ T-cell proliferation, antigen-specific Tc1 cytokine production and specific-tumor killing capacity. In tumor microenvironments, antigen-specific Tc1 induced by the LCpG promoted CTL infiltration, skewed tumor associated macrophages to M1 phenotype, regulated Treg and induced proinflammatory cytokines production in a CTL-derived IFN-γ-dependent manner. In vivo cell depletion and adoptive transfer experiments confirmed that antitumor activity of LCpG included vaccine was mainly dependent on CTL-derived IFN-γ. The anti-tumor efficacy of LCpG was dramatically enhanced when combined with anti-PD1 immunotherapy. LCpG was a promising adjuvant for vaccine formulation which could augment tumor-specific Tc1 activity, and regulate tumor microenvironments.

Matched MeSH terms: Adjuvants, Immunologic
Mucosal and systemic responses of immunogenic vaccines candidates against enteric Escherichia coli infections in ruminants: A review

Lawan A, Jesse FFA, Idris UH, Odhah MN, Arsalan M, Muhammad NA, et al.

Microb Pathog, 2018 Apr;117:175-183.
PMID: 29471137 DOI: 10.1016/j.micpath.2018.02.039

Innumerable Escherichia coli of animal origin are identified, which are of economic significance, likewise, cattle, sheep and goats are the carrier of enterohaemorrhagic E. coli, which are less pathogenic, and can spread to people by way of direct contact and through the contamination of foodstuff or portable drinking water, causing serious illness. The immunization of ruminants has been carried out for ages and is largely acknowledged as the most economical and maintainable process of monitoring E. coli infection in ruminants. Yet, only a limited number of E. coli vaccines are obtainable. Mucosal surfaces are the most important ingress for E. coli and thus mucosal immune responses function as the primary means of fortification. Largely contemporary vaccination processes are done by parenteral administration and merely limited number of E. coli vaccines are inoculated via mucosal itinerary, due to its decreased efficacy. Nevertheless, aiming at maximal mucosal partitions to stimulate defensive immunity at both mucosal compartments and systemic site epitomises a prodigious task. Enormous determinations are involved in order to improve on novel mucosal E. coli vaccines candidate by choosing apposite antigens with potent immunogenicity, manipulating novel mucosal itineraries of inoculation and choosing immune-inducing adjuvants. The target of E. coli mucosal vaccines is to stimulate a comprehensive, effective and defensive immunity by specifically counteracting the antibodies at mucosal linings and by the stimulation of cellular immunity. Furthermore, effective E. coli mucosal vaccine would make vaccination measures stress-free and appropriate for large number of inoculation. On account of contemporary advancement in proteomics, metagenomics, metabolomics and transcriptomics research, a comprehensive appraisal of the immeasurable genes and proteins that were divulged by a bacterium is now in easy reach. Moreover, there exist marvellous prospects in this bourgeoning technologies in comprehending the host bacteria affiliation. Accordingly, the flourishing knowledge could massively guarantee to the progression of immunogenic vaccines against E. coli infections in both humans and animals. This review highlight and expounds on the current prominence of mucosal and systemic immunogenic vaccines for the prevention of E. coli infections in ruminants.

Matched MeSH terms: Adjuvants, Immunologic
Fulltext Effect of Recombinant Zoster Vaccine on Incidence of Herpes Zoster After Autologous Stem Cell Transplantation: A Randomized Clinical Trial

Bastidas A, de la Serna J, El Idrissi M, Oostvogels L, Quittet P, López-Jiménez J, et al.

JAMA, 2019 07 09;322(2):123-133.
PMID: 31287523 DOI: 10.1001/jama.2019.9053

Importance: Herpes zoster, a frequent complication following autologous hematopoietic stem cell transplantation (HSCT), is associated with significant morbidity. A nonlive adjuvanted recombinant zoster vaccine has been developed to prevent posttransplantation zoster.
Objective: To assess the efficacy and adverse event profile of the recombinant zoster vaccine in immunocompromised autologous HSCT recipients.
Design, Setting, and Participants: Phase 3, randomized, observer-blinded study conducted in 167 centers in 28 countries between July 13, 2012, and February 1, 2017, among 1846 patients aged 18 years or older who had undergone recent autologous HSCT.
Interventions: Participants were randomized to receive 2 doses of either recombinant zoster vaccine (n = 922) or placebo (n = 924) administered into the deltoid muscle; the first dose was given 50 to 70 days after transplantation and the second dose 1 to 2 months thereafter.
Main Outcomes and Measures: The primary end point was occurrence of confirmed herpes zoster cases.
Results: Among 1846 autologous HSCT recipients (mean age, 55 years; 688 [37%] women) who received 1 vaccine or placebo dose, 1735 (94%) received a second dose and 1366 (74%) completed the study. During the 21-month median follow-up, at least 1 herpes zoster episode was confirmed in 49 vaccine and 135 placebo recipients (incidence, 30 and 94 per 1000 person-years, respectively), an incidence rate ratio (IRR) of 0.32 (95% CI, 0.22-0.44; P

Matched MeSH terms: Adjuvants, Immunologic
Evaluation of combined Pasteurella vaccines in control of sheep pneumonia

Chandrasekaran S, Hizat K, Saad Z, Johara MY, Yeap PC

Br. Vet. J., 1991 Sep-Oct;147(5):437-43.
PMID: 1959015

The effectiveness of an oil adjuvant vaccine (OAV) incorporating locally isolated strains of Pasteurella haemolytica type 7 and Pasteurella multocida types A and D was compared with that of Carovax (Wellcome Laboratories) in imported cross-bred lambs. The criterion of efficacy was the ability of the vaccines to reduce the extent of pneumonic lesions in vaccinated as against unvaccinated control lambs. The OAV produced at this Institute significantly reduced the lung lesions at P less than 0.05 level compared with its control group when challenged with P. haemolytica alone. However, the vaccine was unsatisfactory against P. multocida or combined P. multocida P. haemolytica challenge. Carovax did not produce any significant reduction in the lung lesions caused by P. haemolytica and/or P. multocida.

Matched MeSH terms: Adjuvants, Immunologic
The Immunomodulatory Potential of Selected Bioactive Plant-Based Compounds in Breast Cancer: A Review

Baraya YS, Wong KK, Yaacob NS

Anticancer Agents Med Chem, 2017;17(6):770-783.
PMID: 27539316 DOI: 10.2174/1871520616666160817111242

Breast cancer has continued to cause high cancer death rates among women worldwide. The use of plants' natural products in breast cancer treatment has received more attention in recent years due to their potentially wider safety margin and the potential to complement conventional chemotherapeutic drugs. Plantbased products have demonstrated anticancer potential through different biological pathways including modulation of the immune system. Immunomodulatory properties of medicinal plants have been shown to mitigate breast cancer cell growth. Different immune cell types participate in this process especially cytotoxic T cells and natural killer cells, and cytokines including chemokines and tumor necrosis factor-α. Medicinal plants such as Glycyrrhiza glabra, Uncaria tomentosa, Camellia sinensis, Panax ginseng, Prunus armenaica (apricot), Allium sativum, Arctium lappa and Curcuma longa were reported to hold strong potential in breast cancer treatment in various parts of the world. Interestingly, research findings have shown that these plants possess bioactive immunomodulators as their main constituents producing the anticancer effects. These immunomodulatory compounds include ajoene, arctigenin, β-carotene, curcumin, epigallocatechin-3-gallate, ginsan, glabridin and quinic acid. In this review, we discussed the ability of these eight immunomodulators in regulating the immune system potentially applicable in breast cancer treatment via anti-inflammatory (curcumin, arctigenin, glabridin and ajoene) and lymphocytes activation (β-carotene, epigallocatechin-3-gallate, quinic acid and ginsan) properties, as well as future research direction in their use for breast cancer treatment.

Matched MeSH terms: Adjuvants, Immunologic/therapeutic use*
Fulltext A Malaysia 97 monovalent foot-and-mouth disease vaccine (>6PD50/dose) protects pigs against challenge with a variant FMDV A SEA-97 lineage virus, 4 and 7 days post vaccination

Nagendrakumar SB, Hong NT, Geoffrey FT, Jacqueline MM, Andrew D, Michelle G, et al.

Vaccine, 2015 Aug 26;33(36):4513-9.
PMID: 26192355 DOI: 10.1016/j.vaccine.2015.07.014

Pigs play a significant role during outbreaks of foot-and-mouth disease (FMD) due to their ability to amplify the virus. It is therefore essential to determine what role vaccination could play to prevent clinical disease and lower virus excretion into the environment. In this study we investigated the efficacy of the double oil emulsion A Malaysia 97 vaccine (>6PD50/dose) against heterologous challenge with an isolate belonging to the A SEA-97 lineage at 4 and 7 days post vaccination (dpv). In addition, we determined whether physical separation of pigs in the same room could prevent virus transmission. Statistically there was no difference in the level of protection offered by 4 and 7 dpv. However, no clinical disease or viral RNA was detected in the blood of pigs challenged 4 dpv, although three of the pigs had antibodies to the non-structural proteins (NSPs), indicating viral replication. Viral RNA was also detected in nasal and saliva swabs, but on very few occasions. Two of the pigs vaccinated seven days prior to challenge had vesicles distal from the injection site, but on the inoculated foot, and two pigs had viral RNA detected in the blood. One pig sero-converted to the NSPs. In contrast, all unvaccinated and inoculated pigs had evidence of infection. No infection occurred in any of the susceptible pigs in the same room, but separated from the infected pigs, indicating that strict biosecurity measures were sufficient under these experimental conditions to prevent virus transmission. However, viral RNA was detected in the nasal swabs of one group of pigs, but apparently not at sufficient levels to cause clinical disease. Vaccination led to a significant decrease in viral RNA in vaccinated pigs compared to unvaccinated and infected pigs, even with this heterologous challenge, and could therefore be considered as a control option during outbreaks.

Matched MeSH terms: Adjuvants, Immunologic/administration & dosage
Fulltext Treatment Access for Gastrointestinal Stromal Tumor in Predominantly Low- and Middle-Income Countries

Briercheck EL, Wrigglesworth JM, Garcia-Gonzalez I, Scheepers C, Ong MC, Venkatesh V, et al.

JAMA Netw Open, 2024 Apr 01;7(4):e244898.
PMID: 38568688 DOI: 10.1001/jamanetworkopen.2024.4898

IMPORTANCE: Gastrointestinal stromal tumor (GIST) is a rare cancer treated with the tyrosine kinase inhibitors imatinib mesylate or sunitinib malate. In general, in low- and middle-income countries (LMICs), access to these treatments is limited.
OBJECTIVE: To describe the demographic characteristics, treatment duration, and survival of patients with GIST in LMICs treated with imatinib and sunitinib through The Max Foundation programs.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective database cohort analysis included patients in 2 access programs administered by The Max Foundation: the Glivec International Patient Assistance Program (GIPAP), from January 1, 2001, to December 31, 2016, and the Max Access Solutions (MAS) program, January 1, 2017, to October 12, 2020. Sixty-six countries in which The Max Foundation facilitates access to imatinib and sunitinib were included. Participants consisted of patients with approved indications for imatinib, including adjuvant therapy in high-risk GIST by pathologic evaluation of resected tumor or biopsy-proven unresectable or metastatic GIST. All patients were reported to have tumors positive for CD117(c-kit) by treating physicians. A total of 9866 patients received treatment for metastatic and/or unresectable disease; 2100 received adjuvant imatinib; 49 received imatinib from another source and were only included in the sunitinib analysis; and 53 received both imatinib and sunitinib through The Max Foundation programs. Data were analyzed from October 13, 2020, to January 30, 2024.
MAIN OUTCOMES AND MEASURES: Demographic and clinical information was reported by treating physicians. Kaplan-Meier analysis was used to estimate time to treatment discontinuation (TTD) and overall survival (OS). An imputation-based informed censoring model estimated events for patients lost to follow-up after treatment with adjuvant imatinib. Patients who were lost to follow-up with metastatic or unresectable disease were presumed deceased.
RESULTS: A total of 12 015 unique patients were included in the analysis (6890 male [57.6%]; median age, 54 [range, 0-100] years). Of these, 2100 patients were treated with imatinib in the adjuvant setting (median age, 54 [range 8-88] years) and 9866 were treated with imatinib for metastatic or unresectable disease (median age, 55 [range, 0-100] years). Male patients comprised 5867 of 9866 patients (59.5%) with metastatic or unresectable disease and 1023 of 2100 patients (48.7%) receiving adjuvant therapy. The median OS with imatinib for unresectable or metastatic disease was 5.8 (95% CI, 5.6-6.1) years, and the median TTD was 4.2 (95% CI, 4.1-4.4) years. The median OS with sunitinib for patients with metastatic or unresectable GIST was 2.0 (95% CI, 1.5-2.5) years; the median TTD was 1.5 (95% CI, 1.0-2.1) years. The 10-year OS rate in the adjuvant setting was 73.8% (95% CI, 67.2%-81.1%).
CONCLUSIONS AND RELEVANCE: In this cohort study of patients with GIST who were predominantly from LMICs and received orally administered therapy through the GIPAP or MAS programs, outcomes were similar to those observed in high-resource countries. These findings underscore the feasibility and relevance of administering oral anticancer therapy to a molecularly defined population in LMICs, addressing a critical gap in cancer care.

Matched MeSH terms: Adjuvants, Immunologic
Preparation and Characterization of Alginate Microparticles Containing a Model Protein for Oral Administration in Gnotobiotic European Sea Bass (Dicentrarchus labrax) Larvae

Yaacob EN, Goethals J, Bajek A, Dierckens K, Bossier P, De Geest BG, et al.

Mar Biotechnol (NY), 2017 Aug;19(4):391-400.
PMID: 28643227 DOI: 10.1007/s10126-017-9758-4

Aquaculture is the fastest growing animal production sector. However, the production of marine fish is still hampered by the high mortality rate in the first few weeks after hatching. Mortality in larvae is often caused by microbial infections. Today, the incorporation of immunostimulants into microparticles provides us new tools to enhance disease resistance in marine larviculture. In this study, we prepared alginate microparticles loaded with the model antigen fluorescein isothiocyanate conjugated-bovine serum albumin. Optimum concentrations of alginate and CaCl2, the correct alginate viscosity and the appropriate preparatory conditions led to the creation of desirable microparticles with the correct size for oral feeding in gnotobiotic European sea bass larvae. The prepared alginate microparticles were stable in sea water and were successfully ingested by gnotobiotic sea bass larvae at day after hatching 7 without causing any negative effects. Results suggest the suitability of this drug delivery system for targeting the innate immune system of fish larvae in order to enhance disease resistance and thus reduce mortality in larviculture.

Matched MeSH terms: Adjuvants, Immunologic
Generation of IgG antibodies against Strongyloides stercoralis in mice via immunization with recombinant antigens A133 and Ss-IR

Wong MTJ, Anuar NS, Noordin R, Tye GJ

Acta Trop, 2024 Mar;251:107122.
PMID: 38246399 DOI: 10.1016/j.actatropica.2024.107122

Strongyloidiasis, caused by the nematode Strongyloides stercoralis, remains a threat to global public health, and a vaccine would be useful to control the disease, especially in developing countries. This study aimed to evaluate the efficacy of recombinant proteins, A133 and Ss-IR, as potential vaccine candidates against strongyloidiasis by investigating the humoral and cellular immune responses in immunized mice. Respective antigens were adjuvanted with Complete Freund's Adjuvant (prime) and Incomplete Freund's Adjuvant (boost) and administered intraperitoneally (prime) and subcutaneously (boost) to female BALB/c mice. For antigen-only doses, only antigens were injected without adjuvants. Altogether, 1 prime dose, 4 booster doses, and 2 antigen-only doses were administered successively. ELISAs were conducted to assess the antibody responses, along with flow cytometry and cytokine ELISA to elucidate the cellular immune responses. Results showed that A133 and Ss-IR induced the production of IgG1 and IgG2a, with A133 generating more robust IgG2a responses than Ss-IR. Flow cytometry findings indicated that effector CD8+T-cells and memory B-cells activity were upregulated significantly for A133 only, whereas cytokine ELISA demonstrated that a Th1/Th2/Th17 mixed cell responses were triggered upon vaccination with either antigen. This preliminary study illustrated the good potential of recombinant A133 and Ss-IR as vaccine candidates against S. stercoralis. It provided information on the probable immune mechanism involved in host defence and the elicitation of protection against S. stercoralis.

Matched MeSH terms: Adjuvants, Immunologic
Self-adjuvanting vaccine against group A streptococcus: application of fibrillized peptide and immunostimulatory lipid as adjuvant

Azmi F, Ahmad Fuaad AA, Giddam AK, Batzloff MR, Good MF, Skwarczynski M, et al.

Bioorg Med Chem, 2014 Nov 15;22(22):6401-8.
PMID: 25438764 DOI: 10.1016/j.bmc.2014.09.042

Peptides are of great interest to be used as vaccine antigens due to their safety, ease of manufacturing and specificity in generating immune response. There have been massive discoveries of peptide antigens over the past decade. However, peptides alone are poorly immunogenic, which demand co-administration with strong adjuvant to enhance their immunogenicity. Recently, fibril-forming peptides such as Q11 and lipoamino acid-based carrier have been identified to induce substantial immune responses when covalently linked to peptide epitope. In this study, we have incorporated either Q11 or lipoamino acids to a peptide epitope (J14) derived from M protein of group A streptococcus to develop self-adjuvanting vaccines. J14, Q11 and lipoamino acids were also conjugated together in a single vaccine construct in an attempt to evaluate the synergy effect of combining multiple adjuvants. Physicochemical characterization demonstrated that the vaccine constructs folded differently and self-assembled into nanoparticles. Significantly, only vaccine constructs containing double copies of lipoamino acids (regardless in conjugation with Q11 or not) were capable to induce significant dendritic cells uptake and subsequent J14-specific antibody responses in non-sizes dependent manners. Q11 had minimal impact in enhancing the immunogenicity of J14 even when it was used in combination with lipoamino acids. These findings highlight the impact of lipoamino acids moiety as a promising immunostimulant carrier and its number of attachment to peptide epitope was found to have a profound effect on the vaccine immunogenicity.

Matched MeSH terms: Adjuvants, Immunologic/chemistry*
Recent progress in adjuvant discovery for peptide-based subunit vaccines

Azmi F, Ahmad Fuaad AA, Skwarczynski M, Toth I

Hum Vaccin Immunother, 2014;10(3):778-96.
PMID: 24300669

Peptide-based subunit vaccines are of great interest in modern immunotherapy as they are safe, easy to produce and well defined. However, peptide antigens produce a relatively weak immune response, and thus require the use of immunostimulants (adjuvants) for optimal efficacy. Developing a safe and effective adjuvant remains a challenge for peptide-based vaccine design. Recent advances in immunology have allowed researchers to have a better understanding of the immunological implication of related diseases, which facilitates more rational design of adjuvant systems. Understanding the molecular structure of the adjuvants allows the establishment of their structure-activity relationships which is useful for the development of next-generation adjuvants. This review summarizes the current state of adjuvants development in the field of synthetic peptide-based vaccines. The structural, chemical and biological properties of adjuvants associated with their immunomodulatory effects are discussed.

Matched MeSH terms: Adjuvants, Immunologic/administration & dosage*; Adjuvants, Immunologic/isolation & purification*
Fulltext Comparison of Fluorinated and Nonfluorinated Lipids in Self-Adjuvanting Delivery Systems for Peptide-Based Vaccines

Hussein WM, Mukaida S, Azmi F, Bartlett S, Olivier C, Batzloff MR, et al.

ACS Med Chem Lett, 2017 Feb 09;8(2):227-232.
PMID: 28197317 DOI: 10.1021/acsmedchemlett.6b00453

Safe immunostimulants (adjuvants) are essential for the development of highly potent peptide-based vaccines. This study examined for the first time whether fluorinated lipids could stimulate humoral immunity in vivo when conjugated to peptide antigen. The impact of fluorination on humoral immunity was tested using a library of peptide-based vaccine candidates against the group A streptococcus (GAS). The fluorinated constructs stimulated similar mouse IgG titers to those elicited by complete Freund's adjuvant (CFA) and were higher than those produced in mice that received the nonfluorinated constructs.

Matched MeSH terms: Adjuvants, Immunologic
The control of haemorrhagic septicaemia in West Malaysia

Thomas J

Trop Anim Health Prod, 1972;4(2):95-101.
PMID: 4671395
Matched MeSH terms: Adjuvants, Immunologic/administration & dosage
Effects of immunostimulators of microbial origin on T cells of pigs vaccinated with attenuated vaccine against Aujeszky's disease

Andrišić M, Žarković I, Šandor K, Vujnović A, Perak Junaković E, Bendelja K, et al.

Vet Immunol Immunopathol, 2022 Jan;243:110365.
PMID: 34920287 DOI: 10.1016/j.vetimm.2021.110365

Aujeszky's disease (AD) is a viral infectious disease caused by Suid herpesvirus 1 (SuHV-1). Vaccination and eradication of AD in domestic pigs is possible using marker vaccines with attenuated or inactivated SuHV-1, or subunit vaccines. However, vaccines with attenuated SuHV-1 have shown to be more potent in inducing strong cell-mediated immune response. The studies have shown that Parapoxvirus ovis, as well as Propionibacterium granulosum with lipopolysacharides (LPS) of Escherichia coli have pronounced immunomodulatory effects and that in combination with the vaccines can induce stronger humoral and cellular immune responses than use of vaccines alone. In our study distribution of peripheral blood T cell subpopulations was analysed after administration of vaccine alone (attenuated SuHV-1), immunostimulators (inactivated Parapoxvirus ovis or combination of an inactivated P. granulosum and detoxified LPS of E. coli) and combinations of vaccine with each immunostimulator to the 12-week old piglets. Throughout the study no significant changes were found in the proportions of γδ and most αβ T cell subpopulations analysed. However, on the seventh day of the study combination of an inactivated P. granulosum and LPS of E. coli with vaccine induced transient but significant increase of the proportions of CD4+CD8α+ and CD4-CD8α+ αβ T cells, that have been strongly associated with early protection of SuHV-1 infected pigs. Our findings indicate that combination of inactivated P. granulosum and detoxified E. coli LPS could be used for enhancement of a cellular immune response induced by vaccines against AD.

Matched MeSH terms: Adjuvants, Immunologic/pharmacology*
Enhancement of ovalbumin-specific IgA responses via oral boosting with antigen co-administered with an aqueous Solanum torvum extract

Israf DA, Lajis NH, Somchit MN, Sulaiman MR

Life Sci, 2004 Jun 11;75(4):397-406.
PMID: 15147827

An experiment was conducted with the objective to enhance mucosal immunity against ovalbumin (OVA) by co-administration of OVA with an aqueous extract from the fruit of Solanum torvum (STE). Five groups of female ICR mice aged approximately 8 weeks at the commencement of the experiment were caged in groups of eight and received various treatments. The treatments included OVA alone, OVA with cholera toxin (CT), and OVA with various doses of STE. Mice were primed intraperitoneally with 500 microg of OVA alone or co-administered with 0.1 microg CT, or with 1 microg STE. All mice were boosted orally via gastric intubation 14 days after priming with 10 mg OVA alone, or co-administered with 10 microg CT or with 10 mg, 1 mg or 0.1 mg STE. One week later all mice were killed and organs obtained for analysis of the immune response. Intestinal, faecal and pulmonary OVA-specific sIgA concentration was significantly increased (p<0.05) in mice that received booster combinations of OVA/CT and OVA with all extract doses (p<0.05). Specific serum IgG titres did not differ significantly between groups. It is concluded that STE can significantly enhance secretory immunity in the intestine to OVA with mucosal homing to the lungs. The adjuvant effect of STE is comparable to that of CT.

Matched MeSH terms: Adjuvants, Immunologic/administration & dosage; Adjuvants, Immunologic/pharmacology*
Immunogenicity and safety of an adjuvanted hepatitis B vaccine in pre-hemodialysis and hemodialysis patients

Tong NK, Beran J, Kee SA, Miguel JL, Sánchez C, Bayas JM, et al.

Kidney Int, 2005 Nov;68(5):2298-303.
PMID: 16221232

Due to their impaired immune system, patients with renal insufficiency have a suboptimal response to hepatitis B (HB) vaccination and frequent boosters are needed to maintain protection. GlaxoSmithKline Biologicals has developed a HB vaccine containing a new adjuvant system AS04 for use in this immunocompromised patient population.

Matched MeSH terms: Adjuvants, Immunologic
Mechanistic insight into immunomodulatory effects of food-functioned plant secondary metabolites

Ali Reza ASM, Nasrin MS, Hossen MA, Rahman MA, Jantan I, Haque MA, et al.

Crit Rev Food Sci Nutr, 2023;63(22):5546-5576.
PMID: 34955042 DOI: 10.1080/10408398.2021.2021138

Medicinally important plant-foods offer a balanced immune function, which is essential for protecting the body against antigenic invasion, mainly by microorganisms. Immunomodulators play pivotal roles in supporting immune function either suppressing or stimulating the immune system's response to invading pathogens. Among different immunomodulators, plant-based secondary metabolites have emerged as high potential not only for immune defense but also for cellular immunoresponsiveness. These natural immunomodulators can be developed into safer alternatives to the clinically used immunosuppressants and immunostimulant cytotoxic drugs which possess serious side effects. Many plants of different species have been reported to possess strong immunomodulating properties. The immunomodulatory effects of plant extracts and their bioactive metabolites have been suggested due to their diverse mechanisms of modulation of the complex immune system and their multifarious molecular targets. Phytochemicals such as alkaloids, flavonoids, terpenoids, carbohydrates and polyphenols have been reported as responsible for the immunomodulatory effects of several medicinal plants. This review illustrates the potent immunomodulatory effects of 65 plant secondary metabolites, including dietary compounds and their underlying mechanisms of action on cellular and humoral immune functions in in vitro and in vivo studies. The clinical potential of some of the compounds to be used for various immune-related disorders is highlighted.

Matched MeSH terms: Adjuvants, Immunologic/metabolism
Fulltext Development of enhanced antibody response toward dual delivery of nano-adjuvant adsorbed human Enterovirus-71 vaccine encapsulated carrier

Saeed MI, Omar AR, Hussein MZ, Elkhidir IM, Sekawi Z

Hum Vaccin Immunother, 2015;11(10):2414-24.
PMID: 26186664 DOI: 10.1080/21645515.2015.1052918

This study introduces a new approach for enhancing immunity toward mucosal vaccines. HEV71 killed vaccine that is formulated with nanosize calcium phosphate adjuvant and encapsulated onto chitosan and alginate delivery carriers was examined for eliciting antibody responses in serum and saliva collected at weeks 0, 1, 3, 5, 7 and 9 for viral-specific IgA & IgG levels and viral neutralizing antibody titers. The antibody responses induced in rabbits by the different formulations delivered by a single (buccal) route were compared to those of dual immunization (intradermal / mucosal) and un-immunized control. Chitosan-loaded vaccine adjuvant induced elevated IgA antibody, while Alginate-adjuvant irreversible bonding sequestered the vaccine and markedly reduced immunogenicity. The induced mucosal and parenteral antibody profiles appeared in an inverse manner of enhanced mucosal IgA antibody accompanied by lower systemic IgG following a single oral immunization route. The combined intradermal and oral dual-immunized group developed an elevated salivary IgA, systemic IgG, and virus neutralizing response. A reduced salivary neutralizing antibody titer was observed and attributed to the continual secretion exchanges in saliva. Designing a successful mucosal delivery formulation needs to take into account the vaccine delivery site, dosage, adjuvant and carrier particle size, charge, and the reversibility of component interactions. The dual immunization seems superior and is a important approach for modulating the antibody response and boosting mucosal protection against HEV71 and similar pathogens based on their transmission mode, tissue tropism and shedding sites. Finally, the study has highlighted the significant role of dual immunization for simultaneous inducing and modulating the systemic and mucosal immune responses to EV71.

Matched MeSH terms: Adjuvants, Immunologic/administration & dosage*
Fulltext A randomized controlled phase 2 trial of the blood stage AMA1-C1/Alhydrogel malaria vaccine in children in Mali

Sagara I, Dicko A, Ellis RD, Fay MP, Diawara SI, Assadou MH, et al.

Vaccine, 2009 May 18;27(23):3090-8.
PMID: 19428923 DOI: 10.1016/j.vaccine.2009.03.014

A double blind, randomized, controlled Phase 2 clinical trial was conducted to assess the safety, immunogenicity, and biologic impact of the vaccine candidate Apical Membrane Antigen 1-Combination 1 (AMA1-C1), adjuvanted with Alhydrogel. Participants were healthy children 2-3 years old living in or near the village of Bancoumana, Mali. A total of 300 children received either the study vaccine or the comparator. No impact of vaccination was seen on the primary endpoint, the frequency of parasitemia measured as episodes >3000/microL/day at risk. There was a negative impact of vaccination on the hemoglobin level during clinical malaria, and mean incidence of hemoglobin <8.5 g/dL, in the direction of lower hemoglobin in the children who received AMA1-C1, although these differences were not significant after correction for multiple tests. These differences were not seen in the second year of transmission.

Matched MeSH terms: Adjuvants, Immunologic/therapeutic use
A Recombinant Subunit HSABA392 as a potential Vaccine for Haemorrhagic septicaemia disease in livestock

Rita DV, Swee KCW, Shamini C, Kang TL, Nurshamimi NR, Hussin AR, et al.

Trop Biomed, 2018 Dec 01;35(4):1075-1086.
PMID: 33601854

Haemorrhagic septicaemia (HS) is a major disease in cattle and buffaloes, caused by certain serotypes of Pasteurella multocida, mainly B and E serotypes. Frequent HS outbreak has a major impact in many Asian countries, including Malaysia, where farmers encounter economic loss due to low milk production as well as death of their livestock. There are four types of vaccines available; broth bacterins, alum precipitated vaccine, aluminium hydroxide gel vaccine and oil adjuvant vaccine (OAV), but these vaccines can only provide short term immunity and therefore need to be administered annually. Hence, the development of a protein vaccine using recombinant antigen can be a potential candidate for the production of HS vaccine that would give longer immunity. We have successfully cloned the ABA392 gene fragment into a protein expression vector, pET-30a. The protein was expressed from our ABA392/pET30a clone and the immunogenicity of the protein has been tested on rats. This vaccine was able to trigger an immune response and therefore has the potential to be tested as suitable vaccine candidate in future studies. It is envisaged that this subunit vaccine will make a significant contribution in the management of HS among livestock in future.

Matched MeSH terms: Adjuvants, Immunologic

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