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Pharmaceutics
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New Adjuvant Technologies for Next-Generation Vaccines
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New Adjuvant Technologies for Next-Generation Vaccines

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Biologics and Biosimilars".

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 10823

Special Issue Editor

Dr. Darío Lirussi

E-Mail Website
Guest Editor
Instituto Nacional de Medicina Tropical – ANLIS – Malbrán (National Institute for Tropical Medicine – INMeT), Puerto Iguazú, Argentina
Interests: vaccines; adjuvants; immunology; delivery technologies; protective responses; molecular adjuvants

Special Issue Information

Dear Colleagues,

This pandemic and post-pandemic brave new world is facing the crude reality of current vaccine technologies (reality being the gigantic effort taken to develop the vaccines that allow us to be protected against SARS-CoV-2/COVID-19). Most of these vaccines were developed based on “in use” or traditional technologies, being protective of mortality but not morbidity or contagion. The mRNA vaccines developed were an exception, representing a promising platform that rapidly developed during the COVID-19; however, they also did not protect completely against infection. In the search for fully protective and more effective vaccines, the development of new adjuvant technologies must be of paramount importance in future vaccines. Not only prophylactic, but also therapeutics vaccines are currently evolving in new treatments by the development of novel adjuvant technologies. In this context, new materials and compounds, such as those from vegetal and fungal origin (that are new, or come to replace classic lipid vehicles), are promising future adjuvants. In this Special Issue of Pharmaceutics, “New Adjuvant Technologies for Next-Generation Vaccines”, we have the opportunity to broadcast to the finest audience our scientific efforts on the research of adjuvant systems that can overcome current vaccine limitations, in the effort of strengthening public health worldwide.

Dr. Darío Lirussi
Guest Editor

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Keywords

  • adjuvant systems
  • antigen delivery
  • signaling molecules
  • plant-derived compounds
  • TLR agonists
  • PAMP
  • molecular adjuvants
  • vaccine platforms
  • liposomes
  • particles in suspension
  • immunomodulators

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Published Papers (5 papers)

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Research

14 pages, 2271 KiB  
Article
Testing S. sonnei GMMA with and without Aluminium Salt-Based Adjuvants in Animal Models
by Francesca Mancini, Valentina Caradonna, Renzo Alfini, Maria Grazia Aruta, Claudia Giorgina Vitali, Gianmarco Gasperini, Diego Piccioli, Francesco Berlanda Scorza, Omar Rossi and Francesca Micoli
Pharmaceutics 2024, 16(4), 568; https://doi.org/10.3390/pharmaceutics16040568 - 22 Apr 2024
Viewed by 1553
Abstract
Shigellosis is one of the leading causes of diarrheal disease in low- and middle-income countries, particularly in young children, and is more often associated with antimicrobial resistance. Therefore, a preventive vaccine against shigellosis is an urgent medical need. We have proposed Generalised Modules [...] Read more.
Shigellosis is one of the leading causes of diarrheal disease in low- and middle-income countries, particularly in young children, and is more often associated with antimicrobial resistance. Therefore, a preventive vaccine against shigellosis is an urgent medical need. We have proposed Generalised Modules for Membrane Antigens (GMMA) as an innovative delivery system for Shigella sonnei O-antigen, and an Alhydrogel formulation (1790GAHB) has been extensively tested in preclinical and clinical studies. Alhydrogel has been used as an adsorbent agent with the main purpose of reducing potential GMMA systemic reactogenicity. However, the immunogenicity and systemic reactogenicity of this GMMA-based vaccine formulated with or without Alhydrogel have never been compared. In this work, we investigated the potential adjuvant effect of aluminium salt-based adjuvants (Alhydrogel and AS37) on S. sonnei GMMA immunogenicity in mice and rabbits, and we found that S. sonnei GMMA alone resulted to be strongly immunogenic. The addition of neither Alhydrogel nor AS37 improved the magnitude or the functionality of vaccine-elicited antibodies. Interestingly, rabbits injected with either S. sonnei GMMA adsorbed on Alhydrogel or S. sonnei GMMA alone showed a limited and transient body temperature increase, returning to baseline values within 24 h after each vaccination. Overall, immunisation with unadsorbed GMMA did not raise any concern for animal health. We believe that these data support the clinical testing of GMMA formulated without Alhydrogel, which would allow for further simplification of GMMA-based vaccine manufacturing. Full article
(This article belongs to the Special Issue New Adjuvant Technologies for Next-Generation Vaccines)
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20 pages, 7028 KiB  
Article
Enhancing Immunogenicity of a Thermostable, Efficacious SARS-CoV-2 Vaccine Formulation through Oligomerization and Adjuvant Choice
by Mohammad Suhail Khan, Virginie Jakob, Randhir Singh, Raju S. Rajmani, Sahil Kumar, Céline Lemoine, Harry Kleanthous, Rajesh P. Ringe, Patrice M. Dubois and Raghavan Varadarajan
Pharmaceutics 2023, 15(12), 2759; https://doi.org/10.3390/pharmaceutics15122759 - 12 Dec 2023
Viewed by 1886
Abstract
Currently deployed SARS-CoV-2 vaccines all require storage at refrigerated or sub-zero temperatures. We demonstrate that after month-long incubation at 37 °C, solubilization, and formulation with squalene-in-water emulsion adjuvant, a stabilized receptor binding domain retains immunogenicity and protective efficacy. We also examine the effects [...] Read more.
Currently deployed SARS-CoV-2 vaccines all require storage at refrigerated or sub-zero temperatures. We demonstrate that after month-long incubation at 37 °C, solubilization, and formulation with squalene-in-water emulsion adjuvant, a stabilized receptor binding domain retains immunogenicity and protective efficacy. We also examine the effects of trimerization of the stabilized RBD, as well as of additional adjuvants, on both B and T-cell responses. The additional emulsion or liposome-based adjuvants contained a synthetic TLR-4 ligand and/or the saponin QS-21. Trimerization enhanced immunogenicity, with significant antibody titers detectable after a single immunization. Saponin-containing adjuvants elicited enhanced immunogenicity relative to both emulsion and aluminum hydroxide adjuvanted formulations lacking these immunostimulants. Trimeric RBD formulated with liposomal based adjuvant containing both TLR-4 ligand and saponin elicited a strongly Th1 biased response, with ~10-fold higher neutralization titers than the corresponding aluminum hydroxide adjuvanted formulation. The SARS-CoV-2 virus is now endemic in humans, and it is likely that periodic updating of vaccine formulations in response to viral evolution will continue to be required to protect vulnerable individuals. In this context, it is desirable to have efficacious, thermostable vaccine formulations to facilitate widespread vaccine coverage, including in low- and middle-income countries, where global access rights to clinically de-risked adjuvants will be important moving forward. Full article
(This article belongs to the Special Issue New Adjuvant Technologies for Next-Generation Vaccines)
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25 pages, 5114 KiB  
Article
Pulmonary Application of Novel Antigen-Loaded Chitosan Nano-Particles Co-Administered with the Mucosal Adjuvant C-Di-AMP Resulted in Enhanced Immune Stimulation and Dose Sparing Capacity
by Thomas Ebensen, Andrea Arntz, Kai Schulze, Andrea Hanefeld, Carlos A. Guzmán and Regina Scherließ
Pharmaceutics 2023, 15(4), 1238; https://doi.org/10.3390/pharmaceutics15041238 - 13 Apr 2023
Cited by 4 | Viewed by 2640
Abstract
The most successful medical intervention for preventing infectious diseases is still vaccination. This effective strategy has resulted in decreased mortality and extended life expectancy. However, there is still a critical need for novel vaccination strategies and vaccines. Antigen cargo delivery by nanoparticle-based carriers [...] Read more.
The most successful medical intervention for preventing infectious diseases is still vaccination. This effective strategy has resulted in decreased mortality and extended life expectancy. However, there is still a critical need for novel vaccination strategies and vaccines. Antigen cargo delivery by nanoparticle-based carriers could promote superior protection against constantly emerging viruses and subsequent diseases. This should be sustained by the induction of vigorous cellular and humoral immunity, capable of acting both at the systemic and mucosal levels. Induction of antigen-specific responses at the portal of entry of pathogens is considered an important scientific challenge. Chitosan, which is widely regarded as a biodegradable, biocompatible and non-toxic material for functionalized nanocarriers, as well as having adjuvant activity, enables antigen administration via less-invasive mucosal routes such as sublingual or pulmonic application route. In this proof of principle study, we evaluate the efficacy of chitosan nanocarriers loaded with the model antigen Ovalbumin (OVA) co-administrated with the STING agonist bis-(3′,5′)-cyclic dimeric adenosine monophosphate (c-di-AMP) given by pulmonary route. Here, BALB/c mice were immunized with four doses of the formulation that stimulates enhanced antigen-specific IgG titers in sera. In addition, this vaccine formulation also promotes a strong Th1/Th17 response characterized by high secretion of IFN-γ, IL-2 and IL-17, as well as induction of CD8+ T cells. Furthermore, the novel formulation exhibited strong dose-sparing capacity, enabling a 90% reduction of the antigen concentration. Altogether, our results suggest that chitosan nanocarriers, in combination with the mucosal adjuvant c-di-AMP, are a promising technology platform for the development of innovative mucosal vaccines against respiratory pathogens (e.g., Influenza or RSV) or for therapeutic vaccines. Full article
(This article belongs to the Special Issue New Adjuvant Technologies for Next-Generation Vaccines)
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19 pages, 1511 KiB  
Article
Protective Efficacy of a Mucosal Influenza Vaccine Formulation Based on the Recombinant Nucleoprotein Co-Administered with a TLR2/6 Agonist BPPcysMPEG
by Maria Victoria Sanchez, Thomas Ebensen, Kai Schulze, Diego Esteban Cargnelutti, Eduardo A. Scodeller and Carlos A. Guzmán
Pharmaceutics 2023, 15(3), 912; https://doi.org/10.3390/pharmaceutics15030912 - 10 Mar 2023
Cited by 1 | Viewed by 2150
Abstract
Current influenza vaccines target highly variable surface glycoproteins; thus, mismatches between vaccine strains and circulating strains often diminish vaccine protection. For this reason, there is still a critical need to develop effective influenza vaccines able to protect also against the drift and shift [...] Read more.
Current influenza vaccines target highly variable surface glycoproteins; thus, mismatches between vaccine strains and circulating strains often diminish vaccine protection. For this reason, there is still a critical need to develop effective influenza vaccines able to protect also against the drift and shift of different variants of influenza viruses. It has been demonstrated that influenza nucleoprotein (NP) is a strong candidate for a universal vaccine, which contributes to providing cross-protection in animal models. In this study, we developed an adjuvanted mucosal vaccine using the recombinant NP (rNP) and the TLR2/6 agonist S-[2,3-bispalmitoyiloxy-(2R)-propyl]-R-cysteinyl-amido-monomethoxyl-poly-ethylene-glycol (BPPcysMPEG). The vaccine efficacy was compared with that observed following parenteral vaccination of mice with the same formulation. Mice vaccinated with 2 doses of rNP alone or co-administered with BPPcysMPEG by the intranasal (i.n.) route showed enhanced antigen-specific humoral and cellular responses. Moreover, NP-specific humoral immune responses, characterized by significant NP-specific IgG and IgG subclass titers in sera and NP-specific IgA titers in mucosal territories, were remarkably increased in mice vaccinated with the adjuvanted formulation as compared with those of the non-adjuvanted vaccination group. The addition of BPPcysMPEG also improved NP-specific cellular responses in vaccinated mice, characterized by robust lymphoproliferation and mixed Th1/Th2/Th17 immune profiles. Finally, it is notable that the immune responses elicited by the novel formulation administered by the i.n. route were able to confer protection against the influenza H1N1 A/Puerto Rico/8/1934 virus. Full article
(This article belongs to the Special Issue New Adjuvant Technologies for Next-Generation Vaccines)
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12 pages, 1544 KiB  
Article
IFN-α/β Signaling Is Required for CDG-Mediated CTL Generation and B Lymphocyte Activation
by Ahmed E. I. Hamouda, Kai Schulze, Thomas Ebensen, Carlos Alberto Guzmán and Darío Lirussi
Pharmaceutics 2022, 14(12), 2821; https://doi.org/10.3390/pharmaceutics14122821 - 16 Dec 2022
Viewed by 1621
Abstract
Among cyclic di-nucleotides (CDN), both cyclic di-AMP (CDA) and di-GMP (CDG) are promising adjuvants and immune modulators. These molecules are not only able to induce profuse antibody production but also predominant T helper 1 and cytotoxic CD8 T lymphocytes (CTL) responses, which enable [...] Read more.
Among cyclic di-nucleotides (CDN), both cyclic di-AMP (CDA) and di-GMP (CDG) are promising adjuvants and immune modulators. These molecules are not only able to induce profuse antibody production but also predominant T helper 1 and cytotoxic CD8 T lymphocytes (CTL) responses, which enable their use for vaccination against intracellular pathogens as well as in cancer immunotherapy. However, for their successful translation into the clinic, a comprehensive understanding of CDN mode of action is still essential. Consistent with evidence in the literature, we show here that IFN-α/β (Type I IFN) is crucial for CDG-mediated B cell activation. We recently determined the key role of type I IFN signaling for CDA-mediated enhancement of immunogenicity. Based on the biological activities of type I IFN, in this study, we hypothesized that it might also be required for CTL induction by CDG. We disclose here the mode of action of type I IFN signaling in CDG-mediated cross-presentation and subsequent CTL generation. Full article
(This article belongs to the Special Issue New Adjuvant Technologies for Next-Generation Vaccines)
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