Pharmaceutics

Research

Jump to: Review

23 pages, 3766 KiB

Open AccessArticle

Safety and Efficacy of the Bordetella bronchiseptica Vaccine Combined with a Vegetable Oil Adjuvant and Multi-Omics Analysis of Its Potential Role in the Protective Response of Rabbits

by Xuemei Cui, Xiangfei Xu, Pan Huang, Guolian Bao and Yan Liu

Pharmaceutics 2022, 14(7), 1434; https://doi.org/10.3390/pharmaceutics14071434 - 8 Jul 2022

Cited by 8 | Viewed by 2125

Abstract

Infectious respiratory diseases caused by Bordetella bronchiseptica (Bb) are seriously endangering the development of the rabbit industry in China. Unfortunately, no licensed vaccines are available for this pathogen. The present study was designed to determine whether the inactivated Bb antigen formulated [...] Read more.

Infectious respiratory diseases caused by Bordetella bronchiseptica (Bb) are seriously endangering the development of the rabbit industry in China. Unfortunately, no licensed vaccines are available for this pathogen. The present study was designed to determine whether the inactivated Bb antigen formulated with vegetable oil adjuvant (named E515) which contains soybean oil, vitamin E, and ginseng saponins, functions as a safe and effective vaccine (E515-Bb) against Bb infection in rabbits. Based on local and systemic reactions, both the E515 adjuvant alone and the E515-Bb vaccine exhibited good safety in rabbits. Immune response analysis implies that rabbits immunized with the E515-Bb vaccine produced significantly higher, earlier, and longer-lasting specific antibody responses and activated Th1/Th2/Th17 cell responses than those immunized with the aluminum hydroxide (Alum)-adjuvanted Bb vaccine (Alum-Bb) or Bb antigen alone. Moreover, the E515-Bb vaccine effectively protected rabbits from Bb infection. Additionally, integrated multi-omics analysis revealed that the immunoprotective effect of the E515-Bb vaccine was achieved through upregulation of the complement and coagulation cascades and cell adhesion molecule (CAM) pathways, and the downregulation of the P53 pathway. Overall, these results indicate that the E515-Bb vaccine is safe, elicits an efficient immune response and provides good protection against Bb infection in rabbits. Thus, the E515-adjuvanted Bb vaccine can be considered a promising candidate vaccine for preventing Bb infection. Full article

(This article belongs to the Special Issue Discovery and Evaluation of Novel Adjuvants for Vaccine Formulations)

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15 pages, 1439 KiB

Open AccessArticle

Transcutaneous Administration of Imiquimod Promotes T and B Cell Differentiation into Effector Cells or Plasma Cells

by Sachiko Hirobe, Taki Yamasaki, Sayami Ito, Ying-Shu Quan, Fumio Kamiyama, Masashi Tachibana and Naoki Okada

Pharmaceutics 2022, 14(2), 385; https://doi.org/10.3390/pharmaceutics14020385 - 10 Feb 2022

Cited by 2 | Viewed by 1953

Abstract

We are interested in promoting the development of transcutaneous immunization using microneedle technology and attempting to apply an adjuvant with transcutaneous immunization to improve the efficacy and reduce the amount of antigen and number of administrations needed. In this study, we collected basic [...] Read more.

We are interested in promoting the development of transcutaneous immunization using microneedle technology and attempting to apply an adjuvant with transcutaneous immunization to improve the efficacy and reduce the amount of antigen and number of administrations needed. In this study, we collected basic information to help elucidate the mechanism responsible for the transcutaneous adjuvant activity of imiquimod (IMQ), which is a ligand of toll-like receptor (TLR) 7. In mouse groups administered ovalbumin (OVA), the OVA-specific IgG antibody titer of the IMQ-adjuvanted group was higher than that of the group administered OVA alone. No immune response bias due to transcutaneous IMQ administration was observed in terms of IgG1 (T helper cell [Th]2-type IgG subclass) and IgG2c (Th1-type IgG subclass) antibody titers. After the initial immunization, the IMQ-adjuvanted group showed increased migration of Langerhans cells to draining lymph nodes (dLNs) and active proliferation of OVA-specific CD4⁺ T cells. Transcutaneously administered IMQ did not affect the direction of CD4⁺ T cell differentiation, while promoted B cell activation and germinal center (GC) B cell differentiation. Immune staining revealed greater GC formation in the dLNs with the IMQ-adjuvanted group than in the OVA-alone group. In the secondary immune response, effector T cells increased in the dLNs and spleen, and effector memory T cells also increased in the spleen in the IMQ-adjuvanted group. In addition, our results suggested that the administration of IMQ enhanced B cell differentiation into plasma cells and GC B cells in the dLNs and spleen. In this study, we partially clarified the mechanism underlying the adjuvant activity of transcutaneously administered IMQ, which is required for the practical application of transcutaneous immunization with IMQ. Full article

(This article belongs to the Special Issue Discovery and Evaluation of Novel Adjuvants for Vaccine Formulations)

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17 pages, 2823 KiB

Open AccessArticle

Cationic and Biocompatible Polymer/Lipid Nanoparticles as Immunoadjuvants

by Yunys Pérez-Betancourt, Péricles Marques Araujo, Bianca de Carvalho Lins Fernandes Távora, Daniele Rodrigues Pereira, Eliana Lima Faquim-Mauro and Ana Maria Carmona-Ribeiro

Pharmaceutics 2021, 13(11), 1859; https://doi.org/10.3390/pharmaceutics13111859 - 4 Nov 2021

Cited by 5 | Viewed by 2506

Abstract

Nanostructures have been of paramount importance for developing immunoadjuvants. They must be cationic and non-cytotoxic, easily assembling with usually oppositely charged antigens such as proteins, haptens or nucleic acids for use in vaccines. We obtained optimal hybrid nanoparticles (NPs) from the biocompatible polymer [...] Read more.

Nanostructures have been of paramount importance for developing immunoadjuvants. They must be cationic and non-cytotoxic, easily assembling with usually oppositely charged antigens such as proteins, haptens or nucleic acids for use in vaccines. We obtained optimal hybrid nanoparticles (NPs) from the biocompatible polymer poly(methyl methacrylate) (PMMA) and the cationic lipid dioctadecyl dimethyl ammonium bromide (DODAB) by emulsion polymerization of methyl methacrylate (MMA) in the presence of DODAB. NPs adsorbed ovalbumin (OVA) as a model antigen and we determined their adjuvant properties. Interestingly, they elicited high double immune responses of the cellular and humoral types overcoming the poor biocompatibility of DODAB-based adjuvants of the bilayer type. The results suggested that the novel adjuvant would be possibly of use in a variety of vaccines. Full article

(This article belongs to the Special Issue Discovery and Evaluation of Novel Adjuvants for Vaccine Formulations)

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12 pages, 940 KiB

Open AccessCommunication

Sulfated Lactosyl Archaeol Archaeosomes Synergize with Poly(I:C) to Enhance the Immunogenicity and Efficacy of a Synthetic Long Peptide-Based Vaccine in a Melanoma Tumor Model

by Bassel Akache, Gerard Agbayani, Felicity C. Stark, Yimei Jia, Renu Dudani, Blair A. Harrison, Lise Deschatelets, Vandana Chandan, Edmond Lam, Usha D. Hemraz, Sophie Régnier, Lakshmi Krishnan and Michael J. McCluskie

Pharmaceutics 2021, 13(2), 257; https://doi.org/10.3390/pharmaceutics13020257 - 12 Feb 2021

Cited by 8 | Viewed by 2481

Abstract

Cancer remains a leading cause of morbidity and mortality worldwide. While novel treatments have improved survival outcomes for some patients, new treatment modalities/platforms are needed to combat a wider variety of tumor types. Cancer vaccines harness the power of the immune system to [...] Read more.

Cancer remains a leading cause of morbidity and mortality worldwide. While novel treatments have improved survival outcomes for some patients, new treatment modalities/platforms are needed to combat a wider variety of tumor types. Cancer vaccines harness the power of the immune system to generate targeted tumor-specific immune responses. Liposomes composed of glycolipids derived from archaea (i.e., archaeosomes) have been shown to be potent adjuvants, inducing robust, long-lasting humoral and cell-mediated immune responses to a variety of antigens. Herein, we evaluated the ability of archaeosomes composed of sulfated lactosyl archaeol (SLA), a semi-synthetic archaeal glycolipid, to enhance the immunogenicity of a synthetic long peptide-based vaccine formulation containing the dominant CD8⁺ T cell epitope, SIINFEKL, from the weakly immunogenic model antigen ovalbumin. One advantage of immunizing with long peptides is the ability to include multiple epitopes, for example, the long peptide antigen was also designed to include the immediately adjacent CD4⁺ epitope, TEWTSSNVMEER. SLA archaeosomes were tested alone or in combination with the toll-like receptor 3 (TLR3) agonist Poly(I:C). Overall, SLA archaeosomes synergized strongly with Poly(I:C) to induce robust antigen-specific CD8⁺ T cell responses, which were highly functional in an in vivo cytolytic assay. Furthermore, immunization with this vaccine formulation suppressed tumor growth and extended mouse survival in a mouse melanoma tumor model. Overall, the combination of SLA archaeosomes and Poly(I:C) appears to be a promising adjuvant system when used along with long peptide-based antigens targeting cancer. Full article

(This article belongs to the Special Issue Discovery and Evaluation of Novel Adjuvants for Vaccine Formulations)

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14 pages, 2181 KiB

Open AccessArticle

Cyclic Di-Adenosine Monophosphate: A Promising Adjuvant Candidate for the Development of Neonatal Vaccines

by Darío Lirussi, Sebastian Felix Weissmann, Thomas Ebensen, Ursula Nitsche-Gloy, Heiko B. G. Franz and Carlos A. Guzmán

Pharmaceutics 2021, 13(2), 188; https://doi.org/10.3390/pharmaceutics13020188 - 1 Feb 2021

Cited by 10 | Viewed by 2756

Abstract

Underdeveloped immunity during the neonatal age makes this period one of the most dangerous during the human lifespan, with infection-related mortality being one of the highest of all age groups. It is also discussed that vaccination during this time window may result in [...] Read more.

Underdeveloped immunity during the neonatal age makes this period one of the most dangerous during the human lifespan, with infection-related mortality being one of the highest of all age groups. It is also discussed that vaccination during this time window may result in tolerance rather than in productive immunity, thus raising concerns about the overall vaccine-mediated protective efficacy. Cyclic di-nucleotides (CDN) are bacterial second messengers that are rapidly sensed by the immune system as a danger signal, allowing the utilization of these molecules as potent activators of the immune response. We have previously shown that cyclic di-adenosine monophosphate (CDA) is a potent and versatile adjuvant capable of promoting humoral and cellular immunity. We characterize here the cytokine profiles elicited by CDA in neonatal cord blood in comparison with other promising neonatal adjuvants, such as the imidazoquinoline resiquimod (R848), which is a synthetic dual TLR7 and TLR8 agonist. We observed superior activity of CDA in eliciting T helper 1 (Th1) and T follicular helper (TfH) cytokines in cells from human cord blood when compared to R848. Additional in vivo studies in mice showed that neonatal priming in a three-dose vaccination schedule is beneficial when CDA is used as a vaccine adjuvant. Humoral antibody titers were significantly higher in mice that received a neonatal prime as compared to those that did not. This effect was absent when using other adjuvants that were reported as suitable for neonatal vaccination. The biological significance of this immune response was assessed by a challenge with a genetically modified influenza H1N1 PR8 virus. The obtained results confirmed that CDA performed better than any other adjuvant tested. Altogether, our results suggest that CDA is a potent adjuvant in vitro on human cord blood, and in vivo in newborn mice, and thus a suitable candidate for the development of neonatal vaccines. Full article

(This article belongs to the Special Issue Discovery and Evaluation of Novel Adjuvants for Vaccine Formulations)

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11 pages, 2587 KiB

Open AccessArticle

Bacterial-Derived Outer Membrane Vesicles are Potent Adjuvants that Drive Humoral and Cellular Immune Responses

by J. Timothy Prior, Christopher Davitt, Jonathan Kurtz, Patrick Gellings, James B. McLachlan and Lisa A. Morici

Pharmaceutics 2021, 13(2), 131; https://doi.org/10.3390/pharmaceutics13020131 - 20 Jan 2021

Cited by 34 | Viewed by 4537

Abstract

Discovery and development of novel adjuvants that can improve existing or next generation vaccine platforms have received considerable interest in recent years. In particular, adjuvants that can elicit both humoral and cellular immune responses would be particularly advantageous because the majority of licensed [...] Read more.

Discovery and development of novel adjuvants that can improve existing or next generation vaccine platforms have received considerable interest in recent years. In particular, adjuvants that can elicit both humoral and cellular immune responses would be particularly advantageous because the majority of licensed vaccines are formulated with aluminum hydroxide (alum) which predominantly promotes antibodies. We previously demonstrated that bacterial-derived outer membrane vesicles (OMV) possess inherent adjuvanticity and drive antigen-specific antibody and cellular immune responses to OMV components. Here, we investigated the ability of OMVs to stimulate innate and adaptive immunity and to function as a stand-alone adjuvant. We show that OMVs are more potent than heat-inactivated and live-attenuated bacteria in driving dendritic cell activation in vitro and in vivo. Mice immunized with OMVs admixed with heterologous peptides generated peptide-specific CD4 and CD8 T cells responses. Notably, OMV adjuvant induced much greater antibody and B cell responses to co-delivered ovalbumin compared to the responses elicited by the adjuvants alum and CpG DNA. Additionally, pre-existing antibodies raised against the OMVs did not impair OMV adjuvanticity upon repeat immunization. These results indicate that vaccines adjuvanted with OMVs elicit robust cellular and humoral immune responses, supporting further development of OMV adjuvant for use in next-generation vaccines. Full article

(This article belongs to the Special Issue Discovery and Evaluation of Novel Adjuvants for Vaccine Formulations)

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13 pages, 2425 KiB

Open AccessArticle

Evaluation of CpG-ODN-Adjuvanted Toxoplasma gondii Virus-Like Particle Vaccine upon One, Two, and Three Immunizations

by Hae-Ji Kang, Ki-Back Chu, Min-Ju Kim, Hyunwoo Park, Hui Jin, Su-Hwa Lee, Eun-Kyung Moon and Fu-Shi Quan

Pharmaceutics 2020, 12(10), 989; https://doi.org/10.3390/pharmaceutics12100989 - 19 Oct 2020

Cited by 10 | Viewed by 2667

Abstract

Successful vaccines against specific pathogens often require multiple immunizations and adjuvant usage. Yet, assessing the protective efficacy of different immunization regimens with adjuvanted Toxoplasma gondii vaccines remains elusive. In this study, we investigated the vaccine efficacy induced by CpG-ODN-adjuvanted T. gondii virus-like particles [...] Read more.

Successful vaccines against specific pathogens often require multiple immunizations and adjuvant usage. Yet, assessing the protective efficacy of different immunization regimens with adjuvanted Toxoplasma gondii vaccines remains elusive. In this study, we investigated the vaccine efficacy induced by CpG-ODN-adjuvanted T. gondii virus-like particles (VLPs) after challenge infection with T. gondii (ME49) in mice (BALB/c) upon one, two, and three immunizations. Immunization with adjuvanted T. gondii VLPs induced higher levels of T. gondii-specific IgG and/or IgA antibody responses, germinal center (GC) B cells, total B cells, and CD4⁺ and CD8⁺ T cells compared with unadjuvanted VLPs. Increasing the number of immunizations was strongly correlated with enhanced protective immunity against T. gondii in mice, with the highest protection being demonstrated in mice thrice-immunized with either adjuvanted T. gondii VLPs or VLPs alone. Notably, lesser bodyweight reductions and cerebral cyst counts were observed in mice receiving multiple immunizations with the adjuvanted VLPs, thereby confirming the effectiveness of adjuvanted boost immunizations. These results demonstrated that multiple immunizations with T. gondii VLPs is an effective approach, and the CpG-ODN can be developed as an effective adjuvant for T. gondii VLP vaccines. Full article

(This article belongs to the Special Issue Discovery and Evaluation of Novel Adjuvants for Vaccine Formulations)

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15 pages, 3722 KiB

Open AccessArticle

Preparation of Squalene Oil-Based Emulsion Adjuvants Employing a Self-Emulsifying Drug Delivery System and Assessment of Mycoplasma hyopneumoniae-Specific Antibody Titers in BALB/c Mice

by Rakesh Bastola, Jo-Eun Seo, Taekwang Keum, Gyubin Noh, Jae Woong Choi, Jong Il Shin, Ju Hun Kim and Sangkil Lee

Pharmaceutics 2019, 11(12), 667; https://doi.org/10.3390/pharmaceutics11120667 - 10 Dec 2019

Cited by 8 | Viewed by 4624

Abstract

In this study, a self-emulsifying drug delivery system (SEDDS) was employed to prepare novel squalene oil-based emulsion adjuvants. Deionized water, 0.01% and 0.02% (w/v) carbomer solutions of C-971P NF and C-940 grades were used to prepare emulsions containing 3%, [...] Read more.

In this study, a self-emulsifying drug delivery system (SEDDS) was employed to prepare novel squalene oil-based emulsion adjuvants. Deionized water, 0.01% and 0.02% (w/v) carbomer solutions of C-971P NF and C-940 grades were used to prepare emulsions containing 3%, 5% and 10% of squalene oil. Altogether 15 candidate emulsions were prepared and used as adjuvants for the delivery of a combination vaccine containing a porcine circovirus type 2 (PCV2) antigen and inactivated Mycoplasma hyopneumoniae (J101 strain) antigen. Most of the emulsions showed droplet sizes in the submicron range and maintained zeta potential values between −40 mV to 0 mV for six months, indicating good physical stability as a vaccine adjuvant. Emulsion-based candidate adjuvants prepared with SEDDS technology stimulated IgG, IgG1 and IgG2a like a currently commercially available adjuvant, Montanide ISA^TM 201, and they were safe and their Mycoplasma hyopneumoniae-specific antibody titers were considered as comparable with that of Montanide ISA^TM 201. Full article

(This article belongs to the Special Issue Discovery and Evaluation of Novel Adjuvants for Vaccine Formulations)

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Review

Jump to: Research

38 pages, 3443 KiB

Open AccessReview

Protein-Based Adjuvants for Vaccines as Immunomodulators of the Innate and Adaptive Immune Response: Current Knowledge, Challenges, and Future Opportunities

by Diego A. Díaz-Dinamarca, Michelle L. Salazar, Byron N. Castillo, Augusto Manubens, Abel E. Vasquez, Fabián Salazar and María Inés Becker

Pharmaceutics 2022, 14(8), 1671; https://doi.org/10.3390/pharmaceutics14081671 - 11 Aug 2022

Cited by 27 | Viewed by 4811

Abstract

New-generation vaccines, formulated with subunits or nucleic acids, are less immunogenic than classical vaccines formulated with live-attenuated or inactivated pathogens. This difference has led to an intensified search for additional potent vaccine adjuvants that meet safety and efficacy criteria and confer long-term protection. [...] Read more.

New-generation vaccines, formulated with subunits or nucleic acids, are less immunogenic than classical vaccines formulated with live-attenuated or inactivated pathogens. This difference has led to an intensified search for additional potent vaccine adjuvants that meet safety and efficacy criteria and confer long-term protection. This review provides an overview of protein-based adjuvants (PBAs) obtained from different organisms, including bacteria, mollusks, plants, and humans. Notably, despite structural differences, all PBAs show significant immunostimulatory properties, eliciting B-cell- and T-cell-mediated immune responses to administered antigens, providing advantages over many currently adopted adjuvant approaches. Furthermore, PBAs are natural biocompatible and biodegradable substances that induce minimal reactogenicity and toxicity and interact with innate immune receptors, enhancing their endocytosis and modulating subsequent adaptive immune responses. We propose that PBAs can contribute to the development of vaccines against complex pathogens, including intracellular pathogens such as Mycobacterium tuberculosis, those with complex life cycles such as Plasmodium falciparum, those that induce host immune dysfunction such as HIV, those that target immunocompromised individuals such as fungi, those with a latent disease phase such as Herpes, those that are antigenically variable such as SARS-CoV-2 and those that undergo continuous evolution, to reduce the likelihood of outbreaks. Full article

(This article belongs to the Special Issue Discovery and Evaluation of Novel Adjuvants for Vaccine Formulations)

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29 pages, 897 KiB

Open AccessReview

An Overview of Nanocarrier-Based Adjuvants for Vaccine Delivery

by Kailash C. Petkar, Suyash M. Patil, Sandip S. Chavhan, Kan Kaneko, Krutika K. Sawant, Nitesh K. Kunda and Imran Y. Saleem

Pharmaceutics 2021, 13(4), 455; https://doi.org/10.3390/pharmaceutics13040455 - 27 Mar 2021

Cited by 69 | Viewed by 7251

Abstract

The development of vaccines is one of the most significant medical accomplishments which has helped to eradicate a large number of diseases. It has undergone an evolutionary process from live attenuated pathogen vaccine to killed whole organisms or inactivated toxins (toxoids), each of [...] Read more.

The development of vaccines is one of the most significant medical accomplishments which has helped to eradicate a large number of diseases. It has undergone an evolutionary process from live attenuated pathogen vaccine to killed whole organisms or inactivated toxins (toxoids), each of them having its own advantages and disadvantages. The crucial parameters in vaccination are the generation of memory response and protection against infection, while an important aspect is the effective delivery of antigen in an intelligent manner to evoke a robust immune response. In this regard, nanotechnology is greatly contributing to developing efficient vaccine adjuvants and delivery systems. These can protect the encapsulated antigen from the host’s in-vivo environment and releasing it in a sustained manner to induce a long-lasting immunostimulatory effect. In view of this, the present review article summarizes nanoscale-based adjuvants and delivery vehicles such as viral vectors, virus-like particles and virosomes; non-viral vectors namely nanoemulsions, lipid nanocarriers, biodegradable and non-degradable nanoparticles, calcium phosphate nanoparticles, colloidally stable nanoparticles, proteosomes; and pattern recognition receptors covering c-type lectin receptors and toll-like receptors. Full article

(This article belongs to the Special Issue Discovery and Evaluation of Novel Adjuvants for Vaccine Formulations)

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26 pages, 9587 KiB

Open AccessReview

Lipid Nanoparticles as Delivery Systems for RNA-Based Vaccines

by Basmah N. Aldosari, Iman M. Alfagih and Alanood S. Almurshedi

Pharmaceutics 2021, 13(2), 206; https://doi.org/10.3390/pharmaceutics13020206 - 2 Feb 2021

Cited by 142 | Viewed by 24534

Abstract

There has been increased interest in the development of RNA-based vaccines for protection against various infectious diseases and also for cancer immunotherapies. Rapid and cost-effective manufacturing methods in addition to potent immune responses observed in preclinical and clinical studies have made mRNA-based vaccines [...] Read more.

There has been increased interest in the development of RNA-based vaccines for protection against various infectious diseases and also for cancer immunotherapies. Rapid and cost-effective manufacturing methods in addition to potent immune responses observed in preclinical and clinical studies have made mRNA-based vaccines promising alternatives to conventional vaccine technologies. However, efficient delivery of these vaccines requires that the mRNA be protected against extracellular degradation. Lipid nanoparticles (LNPs) have been extensively studied as non-viral vectors for the delivery of mRNA to target cells because of their relatively easy and scalable manufacturing processes. This review highlights key advances in the development of LNPs and reviews the application of mRNA-based vaccines formulated in LNPs for use against infectious diseases and cancer. Full article

(This article belongs to the Special Issue Discovery and Evaluation of Novel Adjuvants for Vaccine Formulations)

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22 pages, 1380 KiB

Open AccessReview

Understanding Host Immunity and the Gut Microbiota Inspires the New Development of Vaccines and Adjuvants

by Kyosuke Yakabe, Jun Uchiyama, Masahiro Akiyama and Yun-Gi Kim

Pharmaceutics 2021, 13(2), 163; https://doi.org/10.3390/pharmaceutics13020163 - 26 Jan 2021

Cited by 8 | Viewed by 4124

Abstract

Vaccinations improve the mortality and morbidity rates associated with several infections through the generation of antigen-specific immune responses. Adjuvants are often used together with vaccines to improve immunogenicity. However, the immune responses induced by most on-going vaccines and adjuvants approved for human use [...] Read more.

Vaccinations improve the mortality and morbidity rates associated with several infections through the generation of antigen-specific immune responses. Adjuvants are often used together with vaccines to improve immunogenicity. However, the immune responses induced by most on-going vaccines and adjuvants approved for human use vary in individuals; this is a limitation that must be overcome to improve vaccine efficacy. Several reports have indicated that the symbiotic bacteria, particularly the gut microbiota, impact vaccine-mediated antigen-specific immune responses and promote the induction of nonspecific responses via the “training” of innate immune cells. Therefore, the interaction between gut microbiota and innate immune cells should be considered to ensure the optimal immunogenicity of vaccines and adjuvants. In this review, we first introduce the current knowledge on the immunological mechanisms of vaccines and adjuvants. Subsequently, we discuss how the gut microbiota influences immunity and highlight the relationship between gut microbes and trained innate immunity, vaccines, and adjuvants. Understanding these complex interactions will provide insights into novel vaccine approaches centered on the gut microbiota. Full article

(This article belongs to the Special Issue Discovery and Evaluation of Novel Adjuvants for Vaccine Formulations)

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16 pages, 682 KiB

Open AccessReview

TLR Agonists as Vaccine Adjuvants Targeting Cancer and Infectious Diseases

by Marina Luchner, Sören Reinke and Anita Milicic

Pharmaceutics 2021, 13(2), 142; https://doi.org/10.3390/pharmaceutics13020142 - 22 Jan 2021

Cited by 172 | Viewed by 11313

Abstract

Modern vaccines have largely shifted from using whole, killed or attenuated pathogens to being based on subunit components. Since this diminishes immunogenicity, vaccine adjuvants that enhance the immune response to purified antigens are critically needed. Further advantages of adjuvants include dose sparing, increased [...] Read more.

Modern vaccines have largely shifted from using whole, killed or attenuated pathogens to being based on subunit components. Since this diminishes immunogenicity, vaccine adjuvants that enhance the immune response to purified antigens are critically needed. Further advantages of adjuvants include dose sparing, increased vaccine efficacy in immunocompromised individuals and the potential to protect against highly variable pathogens by broadening the immune response. Due to their ability to link the innate with the adaptive immune response, Toll-like receptor (TLR) agonists are highly promising as adjuvants in vaccines against life-threatening and complex diseases such as cancer, AIDS and malaria. TLRs are transmembrane receptors, which are predominantly expressed by innate immune cells. They can be classified into cell surface (TLR1, TLR2, TLR4, TLR5, TLR6) and intracellular TLRs (TLR3, TLR7, TLR8, TLR9), expressed on endosomal membranes. Besides a transmembrane domain, each TLR possesses a leucine-rich repeat (LRR) segment that mediates PAMP/DAMP recognition and a TIR domain that delivers the downstream signal transduction and initiates an inflammatory response. Thus, TLRs are excellent targets for adjuvants to provide a “danger” signal to induce an effective immune response that leads to long-lasting protection. The present review will elaborate on applications of TLR ligands as vaccine adjuvants and immunotherapeutic agents, with a focus on clinically relevant adjuvants. Full article

(This article belongs to the Special Issue Discovery and Evaluation of Novel Adjuvants for Vaccine Formulations)

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20 pages, 1827 KiB

Open AccessReview

Strategies for Vaccination: Conventional Vaccine Approaches Versus New-Generation Strategies in Combination with Adjuvants

by Abdellatif Bouazzaoui, Ahmed A. H. Abdellatif, Faisal A. Al-Allaf, Neda M. Bogari, Saied Al-Dehlawi and Sameer H. Qari

Pharmaceutics 2021, 13(2), 140; https://doi.org/10.3390/pharmaceutics13020140 - 22 Jan 2021

Cited by 36 | Viewed by 7500

Abstract

The current COVID-19 pandemic, caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has raised significant economic, social, and psychological concerns. The rapid spread of the virus, coupled with the absence of vaccines and antiviral treatments for SARS-CoV-2, has galvanized a major global endeavor [...] Read more.

The current COVID-19 pandemic, caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has raised significant economic, social, and psychological concerns. The rapid spread of the virus, coupled with the absence of vaccines and antiviral treatments for SARS-CoV-2, has galvanized a major global endeavor to develop effective vaccines. Within a matter of just a few months of the initial outbreak, research teams worldwide, adopting a range of different strategies, embarked on a quest to develop effective vaccine that could be effectively used to suppress this virulent pathogen. In this review, we describe conventional approaches to vaccine development, including strategies employing proteins, peptides, and attenuated or inactivated pathogens in combination with adjuvants (including genetic adjuvants). We also present details of the novel strategies that were adopted by different research groups to successfully transfer recombinantly expressed antigens while using viral vectors (adenoviral and retroviral) and non-viral delivery systems, and how recently developed methods have been applied in order to produce vaccines that are based on mRNA, self-amplifying RNA (saRNA), and trans-amplifying RNA (taRNA). Moreover, we discuss the methods that are being used to enhance mRNA stability and protein production, the advantages and disadvantages of different methods, and the challenges that are encountered during the development of effective vaccines. Full article

(This article belongs to the Special Issue Discovery and Evaluation of Novel Adjuvants for Vaccine Formulations)

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13 pages, 833 KiB

Open AccessReview

Promising Adjuvants and Platforms for Influenza Vaccine Development

by Wandi Zhu, Chunhong Dong, Lai Wei and Bao-Zhong Wang

Pharmaceutics 2021, 13(1), 68; https://doi.org/10.3390/pharmaceutics13010068 - 7 Jan 2021

Cited by 26 | Viewed by 5809

Abstract

Influenza is one of the major threats to public health. Current influenza vaccines cannot provide effective protection against drifted or shifted influenza strains. Researchers have considered two important strategies to develop novel influenza vaccines with improved immunogenicity and broader protective efficacy. One is [...] Read more.

Influenza is one of the major threats to public health. Current influenza vaccines cannot provide effective protection against drifted or shifted influenza strains. Researchers have considered two important strategies to develop novel influenza vaccines with improved immunogenicity and broader protective efficacy. One is applying fewer variable viral antigens, such as the haemagglutinin stalk domain. The other is including adjuvants in vaccine formulations. Adjuvants are promising and helpful boosters to promote more rapid and stronger immune responses with a dose-sparing effect. However, few adjuvants are currently licensed for human influenza vaccines, although many potential candidates are in different trials. While many advantages have been observed using adjuvants in influenza vaccine formulations, an improved understanding of the mechanisms underlying viral infection and vaccination-induced immune responses will help to develop new adjuvant candidates. In this review, we summarize the works related to adjuvants in influenza vaccine research that have been used in our studies and other laboratories. The review will provide perspectives for the utilization of adjuvants in developing next-generation and universal influenza vaccines. Full article

(This article belongs to the Special Issue Discovery and Evaluation of Novel Adjuvants for Vaccine Formulations)

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27 pages, 2297 KiB

Open AccessReview

Nanoparticles as Adjuvants and Nanodelivery Systems for mRNA-Based Vaccines

by Iman M. Alfagih, Basmah Aldosari, Bushra AlQuadeib, Alanood Almurshedi and Mariyam M. Alfagih

Pharmaceutics 2021, 13(1), 45; https://doi.org/10.3390/pharmaceutics13010045 - 30 Dec 2020

Cited by 43 | Viewed by 8332

Abstract

Messenger RNA (mRNA)-based vaccines have shown promise against infectious diseases and several types of cancer in the last two decades. Their promise can be attributed to their safety profiles, high potency, and ability to be rapidly and affordably manufactured. Now, many RNA-based vaccines [...] Read more.

Messenger RNA (mRNA)-based vaccines have shown promise against infectious diseases and several types of cancer in the last two decades. Their promise can be attributed to their safety profiles, high potency, and ability to be rapidly and affordably manufactured. Now, many RNA-based vaccines are being evaluated in clinical trials as prophylactic and therapeutic vaccines. However, until recently, their development has been limited by their instability and inefficient in vivo transfection. The nanodelivery system plays a dual function in RNA-based vaccination by acting as a carrier system and as an adjuvant. That is due to its similarity to microorganisms structurally and size-wise; the nanodelivery system can augment the response by the immune system via simulating the natural infection process. Nanodelivery systems allow non-invasive mucosal administration, targeted immune cell delivery, and controlled delivery, reducing the need for multiple administrations. They also allow co-encapsulating with immunostimulators to improve the overall adjuvant capacity. The aim of this review is to discuss the recent developments and applications of biodegradable nanodelivery systems that improve RNA-based vaccine delivery and enhance the immunological response against targeted diseases. Full article

(This article belongs to the Special Issue Discovery and Evaluation of Novel Adjuvants for Vaccine Formulations)

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