A Perspective on the Roles of Adjuvants in Developing Highly Potent COVID-19 Vaccines

Article Medicine, General & Internal

Efficacy of the adjuvanted subunit protein COVID-19 vaccine, SCB-2019: a phase 2 and 3 multicentre, double-blind, randomised, placebo-controlled trial

Lulu Bravo et al.

Summary: The SCB-2019 vaccine, supplemented with CpG and alum, provides significant protection against COVID-19 caused by different SAR-CoV-2 viruses, including the dominant Delta variant.

LANCET (2022)

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Review Virology

Safety and potency of BIV1-CovIran inactivated vaccine candidate for SARS-CoV-2: A preclinical study

Asghar Abdoli et al.

Summary: The study successfully developed a potential SARS-CoV-2 candidate vaccine BIV1-CovIran and demonstrated high efficacy and safety in animal trials.

REVIEWS IN MEDICAL VIROLOGY (2022)

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Article Biophysics

COVID-19 diagnosis - A review of current methods

Meral Yuce et al.

Summary: A fast and accurate self-testing tool for COVID-19 diagnosis is crucial for understanding the global situation and taking appropriate actions. The diagnosis tools available mainly rely on viral gene detection, human antibody detection, and viral antigen detection, with RT-PCR being the most reliable technique.

BIOSENSORS & BIOELECTRONICS (2021)

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Review Microbiology

Learning from the past: development of safe and effective COVID-19 vaccines

Shan Su et al.

Summary: In the development of a COVID-19 vaccine, it is crucial to prioritize safety and efficacy evaluations, drawing lessons from past vaccine development efforts. Su, Du, and Jiang summarize the lessons from previous vaccine development for other viruses, highlighting how mechanisms of vaccine-associated disease enhancement can inform the development of a safe and effective COVID-19 vaccine.

NATURE REVIEWS MICROBIOLOGY (2021)

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Review Pharmacology & Pharmacy

Delivery of STING agonists for adjuvanting subunit vaccines

Simon Van Herck et al.

Summary: This review discusses the mechanisms of STING agonists in vaccination, recent progress in novel STING agonist discovery and delivery strategies, as well as efforts in optimizing the efficacy and minimizing toxicity of STING agonist-assisted subunit vaccines. The future development of STING agonists for adjuvanting subunit vaccines is also discussed.

ADVANCED DRUG DELIVERY REVIEWS (2021)

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Article Chemistry, Multidisciplinary

Sterilizing Immunity against SARS-CoV-2 Infection in Mice by a Single-Shot and Lipid Amphiphile Imidazoquinoline TLR7/8 Agonist-Adjuvanted Recombinant Spike Protein Vaccine**

Sonia Jangra et al.

Summary: IMDQ-PEG-CHOL is an amphiphilic TLR7/8 adjuvant that can enhance immune response, reduce systemic inflammation, and translocate to lymph nodes. When added to vaccines, it induces high levels of antibodies in mice that effectively neutralize viral infections in vitro and in vivo.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2021)

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Article Engineering, Biomedical

Generation of potent cellular and humoral immunity against SARS-CoV-2 antigens via conjugation to a polymeric glyco-adjuvant

Laura T. Gray et al.

Summary: Spike-p(Man-TLR7) vaccination induces robust antigen-specific cellular and humoral responses in mice, generating high and long-lasting titers of antibodies with neutralizing abilities surpassing convalescent human serum. The vaccine also enhances germinal center B cells, antigen-specific antibody secreting cells, activated T follicular helper cells, and polyfunctional Th1-cytokine producing CD4(+) and CD8(+) T cells.

BIOMATERIALS (2021)

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Article Chemistry, Physical

Manganese nanodepot augments host immune response against coronavirus

Yizhe Sun et al.

Summary: Interferon (IFN) responses are crucial for host defense against coronavirus and other viruses. A nanodepot of manganese (nanoMn) based on Mn2+ was successfully fabricated using chemical engineering strategy, enhancing cellular uptake and persistent release of Mn2+ in a pH-sensitive manner, thereby strengthening IFN responses and eliciting broad-spectrum antiviral effects.

NANO RESEARCH (2021)

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Article Medicine, General & Internal

Adjuvanted SARS-CoV-2 spike protein elicits neutralizing antibodies and CD4 T cell responses after a single immunization in mice

Katharina Worzner et al.

Summary: The study evaluated three different adjuvant systems combined with the SARS-CoV2 spike protein and found that they significantly enhanced antibody responses and neutralizing antibody titers. The oil-in-water emulsion system provided the most rapid response, with all adjuvanted groups developing neutralizing antibodies after a single dose. The specific CD4 T cell responses also varied depending on the adjuvant used.

EBIOMEDICINE (2021)

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Article Medicine, General & Internal

Efficacy, safety, and lot-to-lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): interim results of a randomised, double-blind, controlled, phase 3 trial

Raches Ella et al.

Summary: The study reported the clinical efficacy of the BBV152 vaccine against COVID-19 infection in Indian adults. The vaccine demonstrated high efficacy in preventing laboratory-confirmed symptomatic COVID-19 and was well tolerated with no safety concerns raised in this interim analysis.

LANCET (2021)

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Article Infectious Diseases

Prevention of influenza during mismatched seasons in older adults with an MF59-adjuvanted quadrivalent influenza vaccine: a randomised, controlled, multicentre, phase 3 efficacy study

Jiri Beran et al.

Summary: The study aimed to investigate the clinical efficacy of MF59-adjuvanted quadrivalent influenza vaccine in adults aged 65 and older. The vaccine efficacy was higher against influenza cases associated with higher fever, but did not meet the preset standard in seasons with high amounts of vaccine strain mismatch.

LANCET INFECTIOUS DISEASES (2021)

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Article Multidisciplinary Sciences

Preclinical efficacy and safety analysis of gamma-irradiated inactivated SARS-CoV-2 vaccine candidates

Gozde Sir Karakus et al.

Summary: The SARS-CoV-2 vaccines are crucial for reducing disease incidence and mortality. Vaccine models containing GM-CSF induced significant antibody production with neutralization capacity, and the presence of adjuvant was more important in T cell response.

SCIENTIFIC REPORTS (2021)

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Article Cell Biology

A two-adjuvant multiantigen candidate vaccine induces superior protective immune responses against SARS-CoV-2 challenge

Wenwen Jiang et al.

Summary: The developed candidate vaccine combines N protein and prefusion-full S protein, generating stronger systemic and mucosal humoral immunity through the combination of flagellin and cyclic GMP-AMP. Additionally, administering the candidate vaccine via intranasal route can enhance local immune responses in the respiratory tract and protect against lethal SARS-CoV-2 challenge.

CELL REPORTS (2021)

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Article Medicine, General & Internal

Different dose regimens of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373) in younger and older adults: A phase 2 randomized placebo-controlled trial

Neil Formica et al.

Summary: This study confirmed the high immunogenicity and good tolerability of the 2-dose regimen of 5-mu g NVX-CoV2373 in younger adults. Additionally, in older adults, the 2-dose regimen of 5 mu g was also well tolerated and showed sufficient immunogenicity to support its use in late-phase efficacy studies.

PLOS MEDICINE (2021)

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Article Immunology

Manganese salts function as potent adjuvants

Rui Zhang et al.

Summary: The colloidal manganese salt (Mn jelly, MnJ) acts as both an immune potentiator and a delivery system, promoting immune responses by inducing antibody production and CD4(+)/CD8(+) T-cell proliferation and activation. It also shows promise as a mucosal adjuvant, inducing high levels of secretory IgA and proving effective for various antigens, making it a potential candidate for adjuvant use.

CELLULAR & MOLECULAR IMMUNOLOGY (2021)

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Article Immunology

Development of COVID-19 vaccine using a dual Toll-like receptor ligand liposome adjuvant

Mayuresh M. Abhyankar et al.

Summary: This vaccine formulation induced strong systemic neutralizing antibodies in mice, providing complete protection against a lethal challenge and lung injury, as well as virus clearance from the lungs. Additionally, the adjuvanted vaccine elicited systemic and local anti-Spike IgA, which could be a key feature for a COVID-19 vaccine.

NPJ VACCINES (2021)

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Article Infectious Diseases

Safety and immunogenicity of SARS-CoV-2 recombinant protein vaccine formulations in healthy adults: interim results of a randomised, placebo-controlled, phase 1-2 dose-ranging study ,

Paul A. Goepfert et al.

Summary: The CoV2 preS dTM vaccine is being developed against SARS-CoV-2 and the interim results of the first-in-human study show lower than expected immune responses, especially in older age groups, and high reactogenicity after the second dose. Further development of the AS03-adjuvanted candidate vaccine will focus on identifying the optimal antigen formulation and dose.

LANCET INFECTIOUS DISEASES (2021)

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Article Infectious Diseases

Safety and immunogenicity of an MF59-adjuvanted spike glycoprotein-clamp vaccine for SARS-CoV-2: a randomised, double-blind, placebo-controlled, phase 1 trial

Keith J. Chappell et al.

Summary: The study evaluated the safety and immunogenicity of a novel COVID-19 vaccine, showing promising results in both aspects. Adverse reactions were minimal, and the vaccine elicited antigen-specific responses regardless of the dosage.

LANCET INFECTIOUS DISEASES (2021)

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Article Immunology

TLR2 senses the SARS-CoV-2 envelope protein to produce inflammatory cytokines

Min Zheng et al.

Summary: The study revealed that the envelope protein of SARS-CoV-2 is sensed by TLR2, leading to the production of inflammatory cytokines, and the severity of the disease is associated with the expression of TLR2 and MYD88. The findings demonstrate the critical role of TLR2 signaling in promoting proinflammatory cytokine production during coronavirus infection, providing new insights for therapeutic strategies against the ongoing COVID-19 pandemic.

NATURE IMMUNOLOGY (2021)

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Article Microbiology

Inactivated rabies virus vectored SARS-CoV-2 vaccine prevents disease in a Syrian hamster model

Drishya Kurup et al.

Summary: The study developed an inactivated rabies virus vectored vaccine platform, resulting in a vaccine against SARS-CoV-2 named CORAVAX. CORAVAX demonstrated effectiveness in preventing viral replication and lung disease in hamster models, showing potential for robust immune responses in humans.

PLOS PATHOGENS (2021)

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Article Microbiology

Immunogenicity of Adjuvanted Psoralen-Inactivated SARS-CoV-2 Vaccines and SARS-CoV-2 Spike Protein DNA Vaccines in BALB/c Mice

Appavu K. Sundaram et al.

Summary: A novel whole-virus SARS-CoV-2 vaccine (SARS-CoV-2 PsIV) was developed using a new psoralen inactivation method, which showed dose-dependent neutralizing antibody responses in mice when administered with alum or Advax-2 adjuvants. The study suggests that SARS-CoV-2 PsIV with alum promotes a Th2-type response, while SARS-CoV-2 PsIV with Advax-2 promotes a Th1-type response based on the observed cytokine ELISPOT responses.

PATHOGENS (2021)

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Article Medicine, Research & Experimental

Role of toll-like receptor 7/8 pathways in regulation of interferon response and inflammatory mediators during SARS-CoV2 infection and potential therapeutic options

Shetty Ravi Dyavar et al.

Summary: SARS-CoV2 infection leads to decreased interferon production and aggravated inflammation, contributing to COVID-19 pathogenesis. Controlling inflammation without affecting interferon production can reduce the severity of COVID-19.

BIOMEDICINE & PHARMACOTHERAPY (2021)

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Review Chemistry, Medicinal

Imidazole Scaffold Based Compounds in the Development of Therapeutic Drugs

Fanjie Hu et al.

Summary: Imidazole, with its five-membered aromatic heterocyclic ring, can bind with enzymes and receptors through various interactions, promoting anti-tumor, anti-inflammatory, anti-microbial, and anti-viral activities. Recent developments in imidazole derivatives for treating various diseases are reviewed and discussed.

CURRENT TOPICS IN MEDICINAL CHEMISTRY (2021)

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Review Pharmacology & Pharmacy

Intranasal vaccines for SARS-CoV-2: From challenges to potential in COVID-19 management

Vivek P. Chavda et al.

Summary: Intranasal vaccines have advantages in targeting SARS-CoV-2 infection, eliciting immune responses, and avoiding infections, while also convenient for self-administration and storage at ambient temperatures.

DRUG DISCOVERY TODAY (2021)

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Review Biochemistry & Molecular Biology

Platelet Innate Immune Receptors and TLRs: A Double-Edged Sword

Theo Ebermeyer et al.

Summary: Platelets play a crucial role in maintaining vascular integrity and hemostasis. Additionally, they interact with immune cells to modulate immune responses. Through various receptors, platelets are involved in physiological processes, including those associated with pathogens and diseases.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Medicine, General & Internal

Effect of 2 Inactivated SARS-CoV-2 Vaccines on Symptomatic COVID-19 Infection in Adults A Randomized Clinical Trial

Nawal Al Kaabi et al.

Summary: This interim analysis of an ongoing randomized trial in the UAE and Bahrain evaluated the efficacy of two inactivated COVID-19 vaccines in preventing symptomatic cases and adverse events in healthy adults. The study found that both vaccines significantly reduced the risk of symptomatic COVID-19 compared to the control group, with efficacy rates of 72.8% and 78.1%. Serious adverse events were rare across all groups.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2021)

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Article Immunology

Early nasal type I IFN immunity against SARS-CoV-2 is compromised in patients with autoantibodies against type I IFNs

Jonathan Lopez et al.

Summary: The nasal IFN-I/III signature in mildly symptomatic COVID-19 patients correlates with serum IFN-a(2) levels, while critically ill patients with autoantibodies against IFN-I showed low nasal IFN-I/III scores despite high viral loads. Functional assays confirmed the role of autoantibodies in compromising the antiviral effects of IFN-I at the early stages of SARS-CoV-2 infection.

JOURNAL OF EXPERIMENTAL MEDICINE (2021)

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Article Infectious Diseases

Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy children and adolescents: a double-blind, randomised, controlled, phase 1/2 clinical trial

Bihua Han et al.

Summary: The study evaluated the safety, tolerability, and immunogenicity of the candidate COVID-19 vaccine CoronaVac containing inactivated SARS-CoV-2 in children and adolescents aged 3-17 years. The research findings indicate that the 3.0 μg dose induced higher levels of neutralizing antibodies compared to the 1.5 μg dose, supporting the use of the 3.0 μg dose for further studies in this age group.

LANCET INFECTIOUS DISEASES (2021)

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Article Chemistry, Multidisciplinary

Engineering a self-navigated MnARK nanovaccine for inducing potent protective immunity against novel coronavirus

Yaling Wang et al.

Summary: The new nanovaccine containing RBD and MnARK shows stronger neutralizing abilities against infection compared to the Alum-adsorbed RBD vaccine. The co-delivery of RBD antigen and MnARK to lymph nodes promotes cellular internalization and the activation of immune cells.

NANO TODAY (2021)

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Article Multidisciplinary Sciences

Inhibition of elastase enhances the adjuvanticity of alum and promotes anti-SARS-CoV-2 systemic and mucosal immunity

Eunsoo Kim et al.

Summary: The study suggests that inhibiting neutrophil elastase can enhance the efficacy of aluminum-based vaccines by promoting high-affinity antibody production and broader T cell responses, particularly Th1 and Tfh responses. Additionally, suppression of elastase activity can induce mucosal immunity after systemic immunization, and enhance the generation of anti-SARS-CoV-2 antibodies targeting specific epitopes of the spike protein.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Article Cell Biology

Protective antibodies elicited by SARS-CoV-2 spike protein vaccination are boosted in the lung after challenge in nonhuman primates

Joseph R. Francica et al.

Summary: The adjuvanted preS dTM vaccine induced multifunctional humoral responses in NHPs, providing significant protection against SARS-CoV-2. Rapid anamnestic antibody responses in the lung may be a key protective mechanism.

SCIENCE TRANSLATIONAL MEDICINE (2021)

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Article Immunology

Immunisation of ferrets and mice with recombinant SARS-CoV-2 spike protein formulated with Advax-SM adjuvant protects against COVID-19 infection

Lei Li et al.

Summary: The development of Covax-19, a recombinant spike protein vaccine, induced high levels of immune response and protected ferrets from SARS-CoV-2 virus challenge. Results suggest that the vaccine not only protects the lungs from infection but also has the potential to reduce virus transmission.

VACCINE (2021)

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Article Multidisciplinary Sciences

SARS-CoV-2 RBD trimer protein adjuvanted with Alum-3M-052 protects from SARS-CoV-2 infection and immune pathology in the lung

Nanda Kishore Routhu et al.

Summary: Efficient vaccines for SARS-CoV-2 are urgently needed, and the trimeric form of the receptor-binding domain of the virus spike protein combined with alum-3M-052 adjuvant has been shown to protect non-human primates from the disease and inhibit infection.

NATURE COMMUNICATIONS (2021)

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Article Immunology

A Combination Adjuvant for the Induction of Potent Antiviral Immune Responses for a Recombinant SARS-CoV-2 Protein Vaccine

Sonia Jangra et al.

Summary: Developed intranasal adjuvant shows robust immune responses and high levels of neutralizing antibodies against SARS-CoV-2 variants in mice, providing potential cross-protection against future drift variants.

FRONTIERS IN IMMUNOLOGY (2021)

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Article Immunology

A yeast expressed RBD-based SARS-CoV-2 vaccine formulated with 3M-052-alum adjuvant promotes protective efficacy in non-human primates

Maria Pino et al.

Summary: The study demonstrates that a yeast-expressed, RBD-based vaccine with 3M-052-alum adjuvant provides strong immune responses and protection against SARS-CoV-2, significantly reducing virus levels in the respiratory tract and lung inflammation. Vaccination also correlates with decreased viral load and plasma analytes, indicating its potential as a scalable vaccine candidate.

SCIENCE IMMUNOLOGY (2021)

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Article Medicine, Research & Experimental

SARS-CoV-2-associated ssRNAs activate inflammation and immunity via TLR7/8

Valentina Salvi et al.

Summary: The inflammatory and IFN pathways of innate immunity are crucial in the resistance and pathogenesis of COVID-19. Single-stranded RNA fragments from the SARS-CoV-2 genome were identified as direct activators of endosomal TLR7/8 and MyD88 pathway, inducing human DC activation and inflammatory responses. The virus endosomal processing products can potentiate IFN and inflammatory responses, playing a key role in host resistance and COVID-19 pathogenesis.

JCI INSIGHT (2021)

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Article Immunology

COVID-19 Subunit Vaccine with a Combination of TLR1/2 and TLR3 Agonists Induces Robust and Protective Immunity

Soo-Kyung Jeong et al.

Summary: This study demonstrates that SARS-CoV-2 antigens formulated with Toll-like receptor agonists, L-pampo, can induce robust immune responses and reduce viral load in a ferret model, suggesting the potential of being a potent subunit vaccine with protective immunity against SARS-CoV-2.

VACCINES (2021)

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Article Immunology

Progress of the COVID-19 vaccine effort: viruses, vaccines and variants versus efficacy, effectiveness and escape

John S. Tregoning et al.

Summary: The development and rollout of vaccines have brought hope for controlling the COVID-19 pandemic, with vaccines proving highly effective in preventing disease. However, challenges remain in ensuring equitable access to vaccines globally, as well as lessons to be learned for controlling pandemics in the future.

NATURE REVIEWS IMMUNOLOGY (2021)

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Article Medicine, General & Internal

Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18 years or older: A randomized, double-blind, placebo-controlled, phase 1/2 trial

Wanshen Guo et al.

Summary: The study assessed the safety and immunogenicity of an inactivated COVID-19 vaccine in Chinese adults, showing it to be well tolerated and immunogenic in both younger and older adults. Different dosing schedules were evaluated and could be further assessed for long-term safety and efficacy in phase 3 trials.

ECLINICALMEDICINE (2021)

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Article Virology