Mode of action of adjuvants: Implications for vaccine safety and design

Mastelic, Béatris; Ahmed, S. Sohail; Egan, William; Giudice, Giuseppe Del; Golding, Hana; Gust, Ian D.; Neels, Pieter; Reed, Steven G.; Sheets, Rebecca; Siegrist, Claire‐Anne; Lambert, Paul‐Henri

doi:10.1016/j.biologicals.2010.06.002

Cited by 62 publications

(32 citation statements)

References 47 publications

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“…Systemic side effects related to the administration of adjuvants typically prevent their use in human vaccines, and these effects usually occur due to the hyperactivation of the immune system as a result of constant exposure to adjuvant, which causes an intense production of pro-inflammatory cytokines (IL-1, IL-6, TNF-α, IFN-γ, and others). Importantly, these effects may occur after the administration of a cytokine adjuvant or after the use of a molecule and subsequent infection by a microorganism that has the same molecule in its constitution, and therefore, such effects must be considered when choosing an adjuvant for a vaccine formulation (73, 74). …”

Section: Cytokine Fusion With Mtb Proteins and Live Recombinant Vectomentioning

confidence: 99%

Role of Fused Mycobacterium tuberculosis Immunogens and Adjuvants in Modern Tuberculosis Vaccines

2014

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Several approaches have been developed to improve or replace the only available vaccine for tuberculosis (TB), BCG (Bacille Calmette Guerin). The development of subunit protein vaccines is a promising strategy because it combines specificity and safety. In addition, subunit protein vaccines can be designed to have selected immune epitopes associated with immunomodulating components to drive the appropriate immune response. However, the limited antigens present in subunit vaccines reduce their capacity to stimulate a complete immune response compared with vaccines composed of live attenuated or killed microorganisms. This deficiency can be compensated by the incorporation of adjuvants in the vaccine formulation. The fusion of adjuvants with Mycobacterium tuberculosis (Mtb) proteins or immune epitopes has the potential to become the new frontier in the TB vaccine development field. Researchers have addressed this approach by fusing the immune epitopes of their vaccines with molecules such as interleukins, lipids, lipoproteins, and immune stimulatory peptides, which have the potential to enhance the immune response. The fused molecules are being tested as subunit vaccines alone or within live attenuated vector contexts. Therefore, the objectives of this review are to discuss the association of Mtb fusion proteins with adjuvants; Mtb immunogens fused with adjuvants; and cytokine fusion with Mtb proteins and live recombinant vectors expressing cytokines. The incorporation of adjuvant molecules in a vaccine can be complex, and developing a stable fusion with proteins is a challenging task. Overall, the fusion of adjuvants with Mtb epitopes, despite the limited number of studies, is a promising field in vaccine development.

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Section: Cytokine Fusion With Mtb Proteins and Live Recombinant Vectomentioning

confidence: 99%

Role of Fused Mycobacterium tuberculosis Immunogens and Adjuvants in Modern Tuberculosis Vaccines

2014

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“…In addition, an adjuvant should have low toxicity and side effects, allowing it to be widely used in human or veterinary vaccine formulations. Quil-A use in vaccines has been restricted due to its reactogenicity, which includes an expressive hemolytic activity, local reactions and even systemic toxicity [12], [13]. Based on our previous work [9], [10] it was possible to conclude that Q. brasiliensis saponins presented significantly less in vivo and in vitro toxicity when compared to Quil-A, being considered a safer and just as effective alternative adjuvant.…”

Section: Introductionmentioning

confidence: 98%

Alternative Inactivated Poliovirus Vaccines Adjuvanted with Quillaja brasiliensis or Quil-A Saponins Are Equally Effective in Inducing Specific Immune Responses

et al. 2014

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Inactivated polio vaccines (IPV) have an important role at the final stages of poliomyelitis eradication programs, reducing the risks associated with the use of attenuated polio vaccine (OPV). An affordable option to enhance vaccine immunogenicity and reduce costs of IPV may be the use of an effective and renewable adjuvant. In the present study, the adjuvant activity of aqueous extract (AE) and saponin fraction QB-90 from Quillaja brasiliensis using poliovirus antigen as model were analyzed and compared to a preparation adjuvanted with Quil-A, a well-known saponin-based commercial adjuvant. Experimental vaccines were prepared with viral antigen plus saline (control), Quil-A (50 µg), AE (400 µg) or QB-90 (50 µg). Sera from inoculated mice were collected at days 0, 28, 42 and 56 post-inoculation of the first dose of vaccine. Serum levels of specific IgG, IgG1 and IgG2a were significantly enhanced by AE, QB-90 and Quil-A compared to control group on day 56. The magnitude of enhancement was statistically equivalent for QB-90 and Quil-A. The cellular response was evaluated through DTH and analysis of IFN-γ and IL-2 mRNA levels using in vitro reestimulated splenocytes. Results indicated that AE and QB-90 were capable of stimulating the generation of Th1 cells against the administered antigen to the same extent as Quil-A. Mucosal immune response was enhanced by the vaccine adjuvanted with QB-90 as demonstrated by increases of specific IgA titers in bile, feces and vaginal washings, yielding comparable or higher titers than Quil-A. The results obtained indicate that saponins from Q. brasiliensis are potent adjuvants of specific cellular and humoral immune responses and represent a viable option to Quil-A.

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“…However, there have been vaccine unresponsive cases reported in the immunodeficient patients of uremia and other conditions [11-13]. Scientists have been working for applicable new adjuvant for HBV and other diseases [14-17]. CpG ODN can enhance the immune response of live-attenuated or multivalent vaccines that cannot mix with alum.…”

Section: Discussionmentioning

confidence: 99%

Enhanced specific immune responses by CpG DNA in mice immunized with recombinant hepatitis B surface antigen and HB vaccine

Zhang

et al. 2011

Virol J

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BackgroundHepatitis B vaccine adjuvant, alum, is generally used for vaccination although it does not stimulate Th1 immunity and 10% of the population has low or no antibody response. Efforts have been continued to find more efficient vaccine adjuvants for better antibody response as well as stimulation of Th1 immunity.MethodsCpG DNA was used as an adjuvant for recombinant HBsAg to immunize 6- to 8-week-old female BALB/c mice with or without alum for different dosages. The production of HBsAb, CD80 and CD86 from dendritic cells, and cytokines IL-10, IL12, etc., were analyzed and compared for the performance of immunization.Results5-20 μg CpG DNA had the best co-stimulation effect of HBsAb serum conversion for mice vaccinated with recombinant expressed HBsAg. The mice vaccinated with recombinant 20 μg CpG DNA and regular vaccine (containing alum adjuvant) had the highest concentration of antibody production. IL-12b, IL-12a and IL10 mRNA reached to the peak level between 3 and 6 hours after the CpG DNA induction in splenocytes. The expression levels of CD80 and CD86 leucocyte surface molecules were increased with 20 μg CpG DNA alone or with 20 μg CpG DNA and 4 μg HBsAg.ConclusionsOur results confirmed the adjuvant effect of CpG DNA for HBsAg in the mouse model. The increase of IL10 and IL12 production suggested the involvement of Th1 cell activation. The activation of CD80 and CD86 molecules by CpG-ODN might be part of the mechanism of T/B cells coordination and the enhancement of recombinant HBsAg induced immune response.

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Mode of action of adjuvants: Implications for vaccine safety and design

Cited by 62 publications

References 47 publications

Role of Fused Mycobacterium tuberculosis Immunogens and Adjuvants in Modern Tuberculosis Vaccines

Role of Fused Mycobacterium tuberculosis Immunogens and Adjuvants in Modern Tuberculosis Vaccines

Alternative Inactivated Poliovirus Vaccines Adjuvanted with Quillaja brasiliensis or Quil-A Saponins Are Equally Effective in Inducing Specific Immune Responses

Enhanced specific immune responses by CpG DNA in mice immunized with recombinant hepatitis B surface antigen and HB vaccine

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