Effect Of Different Adjuvants Research Articles

The Influence of Adjuvant Type on the Immunogenicity of RBD/N Cocktail Antigens as a Vaccine Candidate against SARS-CoV-2 Virus.

The emerging virus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2 virus), agent of COVID-19, appeared in December 2019 in Wuhan, China, and became a serious threat to global health and public safety. Many COVID-19 vaccines have been approved and licensed around the world. Most of the developed vaccines include S protein and induce an antibody-based immune response. Additionally, T-cell response to the SARS-CoV-2 antigens could be beneficial for combating the infection. The type of immune response is greatly dependent not only on the antigen, but also on adjuvants used in vaccine formulation. Here, we compared the effect of four different adjuvants (AddaS03, Alhydrogel/MPLA, Alhydrogel/ODN2395, Quil A) on the immunogenicity of a mixture of recombinant RBD and N SARS-CoV-2 proteins. We have analyzed the antibody and T-cell response specific to RBD and N proteins and assessed the impact of adjuvants on virus neutralization. Our results clearly indicated that Alhydrogel/MPLA and Alhydrogel/ODN2395 adjuvants elicited the higher titers of specific and cross-reactive antibodies to S protein variants from various SARS-CoV-2 and SARS-CoV-1 strains. Moreover, Alhydrogel/ODN2395 stimulated high cellular response to both antigens, as assessed by IFN-γ production. Importantly, sera collected from mice immunized with RBD/N cocktail in combination with these adjuvants exhibited neutralizing activity against the authentic SARS-CoV-2 virus as well as particles pseudotyped with S protein from various virus variants. The results from our study demonstrate the immunogenic potential of RBD and N antigens and point out the importance of adjuvants selection in vaccine formulation in order to enhance the immunological response. IMPORTANCE Although several COVID-19 vaccines have been approved worldwide, continuous emergence of new SARS-CoV-2 variants calls for new efficient vaccines against them, providing long-lasting immunity. As the immune response after vaccination is dependent not only on antigen used, but also on other vaccine components, e.g., adjuvants, the purpose of this work was to study the effect of different adjuvants on the immunogenicity of RBD/N SARS-CoV-2 cocktail proteins. In this work, it has been shown that immunization with both antigens plus the different adjuvants studied elicited higher Th1 and Th2 responses against RBD and N, which contributed to higher neutralization of the virus. The obtained results can be used for design of new vaccines, not only against SARS-CoV-2, but also against other important viral pathogens.

Impact of adjuvants on the biophysical and functional characteristics of HIV vaccine-elicited antibodies in humans

Adjuvants can alter the magnitude, characteristics, and persistence of the humoral response to protein vaccination. HIV vaccination might benefit from tailored adjuvant choice as raising a durable and protective response to vaccination has been exceptionally challenging. Analysis of trials of partially effective HIV vaccines have identified features of the immune response that correlate with decreased risk, including high titers of V1V2-binding IgG and IgG3 responses with low titers of V1V2-binding IgA responses and enhanced Fc effector functions, notably antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). However, there has been limited opportunity to compare the effect of different adjuvants on these activities in humans. Here, samples from the AVEG015 study, a phase 1 trial in which participants (n = 112) were immunized with gp120SF-2 and one of six different adjuvants or combinations thereof were assessed for antibody titer, biophysical features, and diverse effector functions. Three adjuvants, MF59 + MTP-PE, SAF/2, and SAF/2 + MDP, increased the peak magnitude and durability of antigen-specific IgG3, IgA, FcγR-binding responses and ADCP activity, as compared to alum. While multiple adjuvants increased the titer of IgG, IgG3, and IgA responses, none consistently altered the balance of IgG to IgA or IgG3 to IgA. Linear regression analysis identified biophysical features including gp120-specific IgG and FcγR-binding responses that could predict functional activity, and network analysis identified coordinated aspects of the humoral response. These analyses reveal the ability of adjuvants to drive the character and function of the humoral response despite limitations of small sample size and immune variability in this human clinical trial.

The immunologic effects of different adjuvants on enhancing homologous and cross-protection by influenza virus vaccination in young and aged mice

Abstract Seasonal vaccination is ineffective in the elderly population and in conferring cross-protection against antigenically different influenza viruses. Therefore, the cross-protective efficacy of influenza vaccines needs to be improved. Here, we compared the effects of different adjuvants (QS-21+MPL, CpG+MPL, BCG CWS, Saponin VSA-1, Quil-A, and Alum) on enhancing the immunogenicity and homologous and cross-protection by influenza vaccination in mice. QS-21+MPL adjuvant was most effective in inducing Th1 T cell, cross-reactive IgG, and hemagglutination inhibiting antibody responses to vaccination. QS-21+MPL and CpG+MPL adjuvants exhibited high potency by preventing weight loss and reducing viral loads and conferring enhanced homologous and cross-protection in young and aged mice. BCG cell-wall skeleton (CWS) displayed lower adjuvant efficacy in inducing Th1 IgG responses and conferring cross-protection. VSA-1 (an analog of licensed adjuvant QS-21) exhibited adjuvant effects on enhancing the protective efficacy against homologous and heterosubtypic viruses comparable to QS-21. Saponin Quil-A exhibited adjuvant effects in CD4-deficient mice suggesting a CD4-independent adjuvant mechanism, in contrast to CpG that requires intact CD4 T cells. The findings suggest that QS-21+MPL, CpG+MPL, and VSA-1 exhibit desirable adjuvant properties on enhancing cross-protective humoral and cellular immunity to vaccination, with a unique pattern of innate immune responses, contributing to improved homologous and heterosubtypic protection. This study has significance in better understanding the effects of potent adjuvants on enhancing homologous and cross-protection to influenza vaccination in young and older adults. This study was supported by NIH/NIAID grants AI093772 (S.M.K.), AI154656 (S.M.K), and AI147042 (S.M.K).

Effect of Different Adjuvants on Immune Responses Elicited by Protein-Based Subunit Vaccines against SARS-CoV-2 and Its Delta Variant.

The global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become more serious because of the continuous emergence of variants of concern (VOC), thus calling for the development of broad-spectrum vaccines with greater efficacy. Adjuvants play important roles in enhancing the immunogenicity of protein-based subunit vaccines. In this study, we compared the effect of three adjuvants, including aluminum, nanoparticle manganese and MF59, on the immunogenicity of three protein-based COVID-19 vaccine candidates, including RBD-Fc, RBD and S-trimer. We found that the nanoparticle manganese adjuvant elicited the highest titers of SARS-CoV-2 RBD-specific IgG, IgG1 and IgG2a, as well as neutralizing antibodies against infection by pseudotyped SARS-CoV-2 and its Delta variant. What is more, the nanoparticle manganese adjuvant effectively reduced the viral load of the authentic SARS-CoV-2 and Delta variant in the cell culture supernatants. These results suggest that nanoparticle manganese, known to facilitate cGAS-STING activation, is an optimal adjuvant for protein-based COVID-19 subunit vaccines.

Evaluation of Quil-A, E. coli DNA and Montanide™ ISA 206 adjuvant combination on the antibody response to foot-and-mouth disease vaccine in sheep.

Vaccination is one of the basic strategies in the fight against foot-and-mouth disease (FMD) in endemic regions. Today, commercially available FMD vaccines are prepared with inactive whole virion, which has low immunogenicity. Therefore, considerable effort has been devoted to finding novel adjuvants. Although mineral oils are among the most common adjuvants, it is still difficult to provide along-term and robust immune response. Combined adjuvant systems are currently being studied to solve the problem. Saponins and CpG-ODNs have been shown to increase the immune response to vaccines individually in various studies. In this study, the effect of different adjuvants and their combinations (Quil-A, E. coliDNA, and MontanideTM ISA 206) on total and neutralizing antibody response in sheep was investigated. According to the results, the Quil-A group induced the highest antibody level, followed by the combination of Quil-A and theE. coliDNA group. The group containingE.coliDNA also caused ahigher antibody response than the group containing only MontanideTM ISA 206 for certain days of sampling. These affordable alternatives of saponin and CpG sources can be used individually to increase the potency of the FMD vaccine for mass vaccinations of sheep. Keywords: foot-and-mouth disease; vaccine; adjuvant; Quil-A; E. coli DNA; combination of adjuvants.

Distinct effects of different adjuvants in the mouse model of allergic airway inflammation.

Allergic asthma was typically considered as an inflammatory disease mediated by type 2 immunity. However, recent studies revealed that asthma is a complex disease displaying a variety of phenotypes and endotypes. We examined cellular phenotypes in the mouse model of allergic asthma sensitized with different adjuvants. The aim of our study was to determine immunologic cellular characteristics in mouse asthma models induced by ovalbumin (OVA) and a variety of adjuvants. Mice were sensitized intraperitoneally with the admixture of OVA and various adjuvants such as Alhydrogel (alum), papain, lipopolysaccharide (LPS), or CpG, and subsequently challenged with OVA intranasally. The cells in bronchoalveolar lavage (BAL) fluid, lung, and mediastinal lymph node (mLN) were examined by flow cytometric analyses. In the lung and BAL fluid, the highest eosinophil levels were observed in the alum group while the highest neutrophil levels were detected in the LPS group. Meanwhile, the LPS group exhibited the most elevated levels of both RORγt+ innate lymphoid cells (ILCs) and IL-17A+ Th cells in the lung and mediastinal lymph node. In the lung, the number of T-bet+ ILCs was highest in the papain group whereas the number of IFN-γ+ Th cells was highest in the CpG group. Notable variances are found in the composition of immune cells and expression of cytokines at the site of pathogenesis among the different mouse models of allergic asthma created by the sensitization with different adjuvants.

Distinct single-component adjuvants steer human DC-mediated T-cell polarization via Toll-like receptor signaling toward a potent antiviral immune response

The COVID-19 pandemic highlights the importance of efficient and safe vaccine development. Vaccine adjuvants are essential to boost and tailor the immune response to the corresponding pathogen. To allow for an educated selection, we assessed the effect of different adjuvants on human monocyte-derived dendritic cells (DCs) and their ability to polarize innate and adaptive immune responses. In contrast to commonly used adjuvants, such as aluminum hydroxide, Toll-like receptor (TLR) agonists induced robust phenotypic and functional DC maturation. In a DC-lymphocyte coculture system, we investigated the ensuing immune reactions. While monophosphoryl lipid A synthetic, a TLR4 ligand, induced checkpoint inhibitors indicative for immune exhaustion, the TLR7/8 agonist Resiquimod (R848) induced prominent type-1 interferon and interleukin 6 responses and robust CTL, B-cell, and NK-cell proliferation, which is particularly suited for antiviral immune responses. The recently licensed COVID-19 vaccines, BNT162b and mRNA-1273, are both based on single-stranded RNA. Indeed, we could confirm that the cytokine profile induced by lipid-complexed RNA was almost identical to the pattern induced by R848. Although this awaits further investigation, our results suggest that their efficacy involves the highly efficient antiviral response pattern stimulated by the RNAs' TLR7/8 activation.

Effects of four different adjuvants separately combined with Aeromonas veronii inactivated vaccine on haematoimmunological state, enzymatic activity, inflammatory response and disease resistance in crucian carp

The purpose of the current study was to explore the immunomodulatory effects of different adjuvants combined with inactivated vaccines under Aeromonas veronii TH0426 infection in crucian carp. This study explored the best conditions for A. veronii as an inactivated vaccine, and included an animal safety test. Furthermore, we expressed the flagellin FlaA of the A. veronii TH0426 strain for use as an adjuvant supplemented in the diet. Crucian carp were fed 12 different experimental diets for 35 days, including the administration of 10 different adjuvants and inactivated vaccine combinations (50% aluminum hydroxide gel and inactivated vaccine combination, and inactivated vaccine with 20%, 30%, or 50% glucan, astragalus polysaccharide or flagellin), inactivated vaccine alone, and PBS control without adjuvant and inactivated vaccine. After the 42 day feeding trials, the fish were challenged with A. veronii TH0426, and the survival rate over 14 days was recorded. In addition, flagellin FlaA can be expressed normally in large amounts. All experimental groups produced higher levels of IgM serum titres than the control group in the different feeding cycles. Moreover, the activity of serum ACP, AKP, SOD, and LZM, and the expression of inflammatory factors were significantly increased in the experimental groups compared with the control group. The results of qRT-PCR analysis showed that the transcription levels of the IL-10, IL-1β, IFN-γ and TNF-α genes in heart, liver, spleen and kidney tissues were significantly enhanced by adjuvant treatment, indicating that the addition of adjuvants can significantly promote the body's inflammatory response. In addition, the phagocytic activity of leukocytes in each adjuvant treated group was significantly enhanced compared to that in the groups without adjuvant. After the A. veronii challenge, the survival rate of all adjuvant-treated groups was significantly higher than that of the control group, and the 50% flagellin adjuvant group had the highest rate of 78.37%. Overall, our findings strongly indicate that adjuvants not only significantly improve the body's immunity, but also exhibit a strong anti-infection ability. Importantly, this work provides a new perspective for the prevention and control of aquaculture diseases.

Study on the effect of different adjuvants on dimethomorph against lettuce downy mildew

Study on the effect of different adjuvants on dimethomorph against lettuce downy mildew

Modeling human adaptive immune responses with tonsil organoids.

Most of what we know about adaptive immunity has come from inbred mouse studies, using methods that are often difficult or impossible to confirm in humans. In addition, vaccine responses in mice are often poorly predictive of responses to those same vaccines in humans. Here we use human tonsils, readily available lymphoid organs, to develop a functional organotypic system that recapitulates key germinal center features in vitro, including the production of antigen-specific antibodies, somatic hypermutation and affinity maturation, plasmablast differentiation and class-switch recombination. We use this system to define the essential cellular components necessary to produce an influenza vaccine response. We also show that it can be used to evaluate humoral immune responses to two priming antigens, rabies vaccine and an adenovirus-based severe acute respiratory syndrome coronavirus 2 vaccine, and to assess the effects of different adjuvants. This system should prove useful for studying critical mechanisms underlying adaptive immunity in much greater depth than previously possible and to rapidly test vaccine candidates and adjuvants in an entirely human system.

Effect of Different Adjuvants on the Longevity and Strength of Humoral and Cellular Immune Responses to the HCV Envelope Glycoproteins.

Infection by Hepatitis C virus (HCV) can lead to liver cirrhosis/hepatocellular carcinoma and remains a major cause of serious disease morbidity and mortality worldwide. However, current treatment regimens remain inaccessible to most patients, particularly in developing countries, and, therefore, the development of a novel vaccine capable of protecting subjects from chronic infection by HCV could greatly reduce the rates of HCV infection, subsequent liver pathogenesis, and in some cases death. Herein, we evaluated two different semi-synthetic archaeosome formulations as an adjuvant to the E1/E2 HCV envelope protein in a murine model and compared antigen-specific humoral (levels of anti-E1/E2 IgG and HCV pseudoparticle neutralization) and cellular responses (numbers of antigen-specific cytokine-producing T cells) to those generated with adjuvant formulations composed of mimetics of commercial adjuvants including a squalene oil-in-water emulsion, aluminum hydroxide/monophosphoryl lipid A (MPLA) and liposome/MPLA/QS-21. In addition, we measured the longevity of these responses, tracking humoral, and cellular responses up to 6 months following vaccination. Overall, we show that the strength and longevity of anti-HCV responses can be influenced by adjuvant selection. In particular, a simple admixed sulfated S-lactosylarchaeol (SLA) archaeosome formulation generated strong levels of HCV neutralizing antibodies and polyfunctional antigen-specific CD4 T cells producing multiple cytokines such as IFN-γ, TNF-α, and IL-2. While liposome/MPLA/QS-21 as adjuvant generated superior cellular responses, the SLA E1/E2 admixed formulation was superior or equivalent to the other tested formulations in all immune parameters tested.

Effect of different adjuvants on various immune cells and cytokines in allergic asthma mouse model

Abstract Allergic asthma is a complex chronic disease which displays combined traits referred to as Th2 mediated eosinophilic allergy, ILC2 mediated allergy, and Th17 cell mediated neutrophilic allergy. In our current study of allergic asthma model, the populations of immune cells related to as well as outside of the Th2 immune response were analyzed for the ratio of cytokines in IL-4, IL5, IL17A and IFN-γ expressing CD4+ T cells utilizing of BALB/c mice sensitized with ovalbumin and a different adjuvant such as Alhydrogel (alum), papain, lipopolysaccharide (LPS), and CpG. In lung and bronchoalveolar lavage fluid, the percentage of eosinophils was lower in groups injected with LPS and papain than those with no adjuvant. In contrast, the injection of LPS and papain increased the percentage of neutrophils when compared to the no adjuvant group. The number of B cells in alum-injected group was higher than those of other groups. Although the percentage of innate lymphoid cells (ILCs) increased slightly for ILC1 and ILC2 in the group injected with papain, the other adjuvants did not cause any differences. After PMA/ionomycin stimulation, the ratio of IL-4 expressing CD4+ T cells in the papain-injected group increased significantly while the other adjuvant groups showed little or no changes. The production of IL-17A in CD4+ T cells increased in LPS-injected group and that of IFN-gamma also increased in CpG-injected group. Our results suggest that many distinct allergic asthma mouse models can be established by specific sensitization protocols exploiting different adjuvants, thus representing the complexity of clinical symptoms.

The influence of adjuvant on UreB protection against Helicobacter pylori through the diversity of CD4+ T-cell epitope repertoire.

Adjuvants are widely used to enhance the effects of vaccines against pathogen infections. Interestingly, different adjuvants and vaccination routes usually induce dissimilar immune responses, and can even have completely opposite effects. The mechanism remains unclear. In this study, urease B subunit (UreB), an antigen of Helicobacter pylori (H. pylori) that can induce protective immune responses, was used as a model to vaccinate mice. We investigated the effects of different adjuvants and routes on consequent T cell epitope-specific targeting and protection against H. pylori infection. Comparison of the protective effects of UreB, administered either subcutaneously (sc) or intranasally (in), with the adjuvants AddaVax (sc), Complete Freund’s adjuvant (CFA; sc), or CpG oligonucleotide (CpG; sc or in), indicated that only CFA (sc) and CpG (in) were protective. Protective vaccines induced T cells targeting epitopes that differed from that targeted by control vaccination. Subsequent peptide vaccination demonstrated that only two of the identified epitopes were protective: UreB373–385 and UreB317–329. Overall, we found that both adjuvant and vaccination route affected the T cell response repertoire to antigen epitopes. The data obtained in this study contribute to improved characterization of the relationship between adjuvants, routes of vaccination, and epitope-specific T cell response repertoires.

The Effect of Magnesium Sulfate on Postoperative Pain in Upper Limb Surgeries by Supraclavicular Block Under Ultrasound Guidance.

BackgroundPrevious studies have been conducted to evaluate the effect of different adjuvants on brachial plexus block.ObjectivesThis study investigated the effect of adding magnesium sulfate to lidocaine on postoperative pain in upper limb surgeries by supraclavicular brachial plexus block under ultrasound guidance.MethodsThis study was carried out on patients who were candidate for upper limb surgeries. This was a controlled double-blind study conducted on a number of 52 patients aged 18 - 75 years with ASA class I or II. The first group (M) received lidocaine 1% (4 mg/kg) plus fentanyl 50 micg and magnesium sulfate 20% (5 mL) while the second group (N) received lidocaine 1% (4 mg/kg) plus fentanyl 50 micg and normal saline (5 mL) to supraclavicular brachial plexus block under ultrasound guidance. Postoperative pain was evaluated by visual analog scale (VAS) until 24 hours. Sensory and motor blocks onset and duration, rescue analgesics, hemodynamic variables, and side effects were recorded for all the patients.ResultsPostoperative VAS values at 24 hours were significantly lower in group M than group N (P < 0.0001). Sensory and Motor blocks onset and duration were statistically longer in group M than group N (P < 0.0001).ConclusionsThe addition of magnesium sulfate to lidocaine decreased the postoperative pain and increased the onset and duration of sensory and motor blocks in supraclavicular brachial plexus block under ultrasound guidance in upper limb surgeries.

Study the effect of different adjuvants on inactivated Equine herpesvirus-1 vaccine

Study the effect of different adjuvants on inactivated Equine herpesvirus-1 vaccine

A mouse model of luciferase-transfected stromal cells of giant cell tumor of bone

A major barrier towards the study of the effects of drugs on Giant Cell Tumor of Bone (GCT) has been the lack of an animal model. In this study, we created an animal model in which GCT stromal cells survived and functioned as proliferating neoplastic cells. A proliferative cell line of GCT stromal cells was used to create a stable and luciferase-transduced cell line, Luc-G33. The cell line was characterized and was found that there were no significant differences on cell proliferation rate and recruitment of monocytes when compared with the wild type GCT stromal cells. We delivered the Luc-G33 cells either subcutaneously on the back or to the tibiae of the nude mice. The presence of viable Luc-G33 cells was assessed using real-time live imaging by the IVIS 200 bioluminescent imaging (BLI) system. The tumor cells initially propagated and remained viable on site for 7 weeks in the subcutaneous tumor model. We also tested in vivo antitumor effects of Zoledronate (ZOL) and Geranylgeranyl transferase-I inhibitor (GGTI-298) alone or their combinations in Luc-G33-transplanted nude mice. ZOL alone at 400 µg/kg and the co-treatment of ZOL at 400 µg/kg and GGTI-298 at 1.16 mg/kg reduced tumor cell viability in the model. Furthermore, the anti-tumor effects by ZOL, GGTI-298 and the co-treatment in subcutaneous tumor model were also confirmed by immunohistochemical (IHC) staining. In conclusion, we established a nude mice model of GCT stromal cells which allows non-invasive, real-time assessments of tumor development and testing the in vivo effects of different adjuvants for treating GCT.

Effect of Different Adjuvants on Protection and Side-Effects Induced by Helicobacter suis Whole-Cell Lysate Vaccination.

Helicobacter suis (H. suis) is a widespread porcine gastric pathogen, which is also of zoonotic importance. The first goal of this study was to investigate the efficacy of several vaccine adjuvants (CpG-DNA, Curdlan, Freund’s Complete and Incomplete, Cholera toxin), administered either subcutaneously or intranasally along with H. suis whole-cell lysate, to protect against subsequent H. suis challenge in a BALB/c infection model. Subcutaneous immunization with Freund’s complete (FC)/lysate and intranasal immunization with Cholera toxin (CT)/lysate were shown to be the best options for vaccination against H. suis, as determined by the amount of colonizing H. suis bacteria in the stomach, although adverse effects such as post-immunization gastritis/pseudo-pyloric metaplasia and increased mortality were observed, respectively. Therefore, we decided to test alternative strategies, including sublingual vaccine administration, to reduce the unwanted side-effects. A CCR4 antagonist that transiently inhibits the migration of regulatory T cells was also included as a new adjuvant in this second study. Results confirmed that immunization with CT (intranasally or sublingually) is among the most effective vaccination protocols, but increased mortality was still observed. In the groups immunized subcutaneously with FC/lysate and CCR4 antagonist/lysate, a significant protection was observed. Compared to the FC/lysate immunized group, gastric pseudo-pyloric metaplasia was less severe or even absent in the CCR4 antagonist/lysate immunized group. In general, an inverse correlation was observed between IFN-γ, IL-4, IL-17, KC, MIP-2 and LIX mRNA expression and H. suis colonization density, whereas lower IL-10 expression levels were observed in partially protected animals.

The Effect of Different Adjuvants on Immune Parameters and Protection following Vaccination of Sheep with a Larval-Specific Antigen of the Gastrointestinal Nematode, Haemonchus contortus

It has recently been recognised that vaccine adjuvants play a critical role in directing the nature of a vaccine induced effector response. In the present study, several adjuvants were evaluated for their ability to protect sheep after field vaccination with the larval-specific Haemonchus contortus antigen, HcsL3. Using a suboptimal antigen dose, aluminium adjuvant was shown to reduce the cumulative faecal egg counts (cFEC) and worm burden by 23% and 25% respectively, in agreement with a previous study. The addition of Quil A to the aluminium-adjuvanted vaccine brought cFEC back to control levels. Vaccination with the adjuvant DEAE-dextran almost doubled the protection compared to the aluminium-adjuvanted vaccine resulting in 40% and 41% reduction in cFEC and worm counts compared to controls. Examination of skin responses following i.d. injection of exsheathed L3, revealed that cFEC was negatively correlated with wheal size and tissue eosinophils for the DEAE-dextran and aluminium-adjuvanted groups respectively. These studies have for the first time shown the potential of DEAE-dextran adjuvant for helminth vaccines, and discovered significant cellular correlates of vaccine-induced protection.

Effects of Different Adjuvants in the Context of Intramuscular and Intranasal Routes on Humoral and Cellular Immune Responses Induced by Detergent-Split A/H3N2 Influenza Vaccines in Mice

Influenza A/H3N2 viruses have caused the most severe epidemics since 1968 despite current immunization programs with inactivated vaccines. We undertook a side-by-side preclinical evaluation of different adjuvants (Alum, AS03, and Protollin) and routes of administration (intramuscular [i.m.] and intranasal [i.n.]) for assessing their effect on the immunogenicity and cross-reactivity of inactivated split vaccines (A/H3N2/New York/55/2004). Humoral and T cell-mediated immune responses against the homologous virus and a heterologous drifted strain (A/H3N2/Wisconsin/67/2005) were measured in BALB/c mice at 2, 6, and 19 weeks postboost. The AS03- and Alum-adjuvanted i.m. vaccines induced at least an 8-fold increase over the nonadjuvanted vaccine in functional antibody titers against both the homotypic and heterotypic strains and low IgG2a and high IgG1 levels, suggesting a mixed Th1/Th2 response with a Th2 trend. The Protollin-adjuvanted i.n. vaccine induced the lowest IgG1/IgG2a ratio, which is indicative of a mixed Th1/Th2-type profile with a Th1 trend. This adjuvanted vaccine was the only vaccine to stimulate a mucosal IgA response. Whatever the timing after the boost, both hemagglutination inhibition (HAI) and microneutralization (MN) titers were higher with the AS03-adjuvanted i.m. vaccine than with the protollin-adjuvanted i.n. vaccine. Finally, the Alum-adjuvanted i.m. vaccine and the lower-dose Protollin-adjuvanted i.n. vaccine elicited significantly higher CD4(+) Th1 and Th2 responses and more gamma interferon (IFN-γ)-producing CD8(+) T cells than the nonadjuvanted vaccine. Our data indicate that the adjuvanted vaccines tested in this study can elicit stronger, more persistent, and broader immune responses against A/H3N2 strains than nonadjuvanted inactivated influenza vaccines.

Study on the immune enhancement of different immunoadjuvants used in the pentavalent vaccine for turbots

In this study, we investigated the immune enhancing effects of different adjuvants used in a pentavalent vaccine for turbots. The pentavalent vaccine consisted of inactive bacterial cells from five common pathogenic strains ( Vibrio anguillarum, Vibrio scophtalmi, Edwardsiella tarda, Vibrio harveyi and Vibrio alginolyticus) and the adjuvants were astragalus polysaccharides (APS), propolis, and the Freund’s complete adjuvant (FCA). Turbots were immunized with the pentavalent vaccine alone or with one of the adjuvants, and the immune efficiency was evaluated by measuring the activities of lysozyme (LSZ) and superoxide dismutase (SOD), and serum antibody titers. Fish were also challenged with the pathogens after immunization and the relative percent survival (RPS) was assessed. Our results showed that APS, propolis, and FCA had significant immune-enhancing effects on turbots as shown by the higher titers of antibodies against the pathogens, increased LSZ and SOD activities, and enhanced RPS after challenge with pathogens. Among the three adjuvants, FCA had the most significant immune synergistic effects with the vaccine, and APS and propolis had lower and similar immune synergies.