Prospects on Repurposing a Live Attenuated Vaccine for the Control of Unrelated Infections

Seo, Sang‐Uk; Seong, Baik-Lin

doi:10.3389/fimmu.2022.877845

Cited by 11 publications

(6 citation statements)

References 132 publications

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“…Combining the two above strategies, live attenuated vaccines could be used for the immediate mitigation and control of unexpected pandemic outbreaks before prophylactic vaccines and/or pathogen-specific therapies are developed [ 10 ]. The proof of principle of this idea was demonstrated using a bivalent oral poliovirus vaccine (bOPV), which significantly reduced the number of COVID-19 cases compared to placebo [ 11 ].…”

Section: Repurposing Is a Drug Development Strategymentioning

confidence: 99%

Combination Therapy for the Treatment of Shingles with an Immunostimulatory Vaccine Virus and Acyclovir

Bakács

Sandig²,

Kovesdi³

2023

Pharmaceuticals

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Practically the entire global population is infected by herpesviruses that establish lifelong latency and can be reactivated. Alpha-herpesviruses, herpes simplex viruses 1 and 2 (HSV-1/HSV-2) and varicella zoster virus (VZV), establish latency in sensory neurons and then reactivate to infect epithelial cells in the mucosa or skin, resulting in a vesicular rash. Licensed antivirals inhibit virus replication, but do not affect latency. On reactivation, VZV causes herpes zoster, also known as shingles. The 76-year-old first author of this paper published an autobiography of his own severe herpes zoster ophthalmicus (HZO) infection with orbital edema, which is considered an emergency condition. Acyclovir (ACV) treatment was complemented with an immunostimulatory viral therapy, which resolved most symptoms within a few days. The orally administered live-attenuated infectious bursal disease vaccine virus (IBDV) delivers its double-stranded RNA (dsRNA) cargo to host cells and activates the natural antiviral interferon (IFN) gene defense system from within the host cells. IBDV has already been demonstrated to be safe and effective against five different families of viruses, hepatitis A virus (HAV), hepatitis B and C virus (HBV/HCV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and varicella zoster virus (VZV). Here we propose a short phase I/II trial in elderly shingles patients who will be assigned to receive either ACV monotherapy or ACV combined with R903/78, an attenuated immunostimulatory IBDV strain. The primary endpoints will be safety, but the efficacy of the combination therapy against the ACV monotherapy also will be assessed.

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Section: Repurposing Is a Drug Development Strategymentioning

confidence: 99%

Combination Therapy for the Treatment of Shingles with an Immunostimulatory Vaccine Virus and Acyclovir

Bakács

Sandig²,

Kovesdi³

2023

Pharmaceuticals

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“…Whole pathogen vaccines are the most common and have shown high potency against viruses, but they require sensitive analytical tools and strict controls during production to prevent the risk of infection. − In addition, due to the use of entire pathogens, they can induce off-target immune responses toward undesired or highly variable epitopes. This could promote antibody-dependent enhancement of viral infections, or render vaccines less or ineffective against viral mutations, necessitating the update of vaccines. − In contrast, nucleic acid vaccines and subunit vaccines do not carry the risk of infection and can be designed to minimize off-target responses by using only specific epitopes. Nucleic acid vaccines, especially mRNA vaccines, have made great advancements in vaccine effectiveness against Covid-19 cases and severity.…”

Section: Introductionmentioning

confidence: 99%

Effect of Antigen Structure in Subunit Vaccine Nanoparticles on Humoral Immune Responses

Park

Champion

2023

ACS Biomater. Sci. Eng.

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Subunit vaccines offer numerous attractive features, including good safety profiles and well-defined components with highly characterized properties because they do not contain whole pathogens. However, vaccine platforms based on one or few selected antigens are often poorly immunogenic. Several advances have been made in improving the effectiveness of subunit vaccines, including nanoparticle formulation and/or co-administration with adjuvants. Desolvation of antigens into nanoparticles is one approach that has been successful in eliciting protective immune responses. Despite this advance, damage to the antigen structure by desolvation can compromise the recognition of conformational antigens by B cells and the subsequent humoral response. Here, we used ovalbumin as a model antigen to demonstrate enhanced efficacy of subunit vaccines by preserving antigen structures in nanoparticles. An altered antigen structure due to desolvation was first validated by GROMACS and circular dichroism. Desolvant-free nanoparticles with a stable ovalbumin structure were successfully synthesized by directly cross-linking ovalbumin or using ammonium sulfate to form nanoclusters. Alternatively, desolvated OVA nanoparticles were coated with a layer of OVA after desolvation. Vaccination with salt-precipitated nanoparticles increased OVA-specific IgG titers 4.2- and 22-fold compared to the desolvated and coated nanoparticles, respectively. In addition, enhanced affinity maturation by both salt precipitated and coated nanoparticles was displayed in contrast to desolvated nanoparticles. These results demonstrate both that salt-precipitated antigen nanoparticles are a potential new vaccine platform with significantly improved humoral immunity and a functional value of preserving antigen structures in vaccine nanoparticle design.

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“…Live attenuated vaccines have been studied as a potential solution for addressing bacterial pathogens that have become resistant to various antibiotics in the context of AMR. A live attenuated vaccine that targets AMR is exemplified by the Salmonella vaccine that has been attenuated ( Seo and Seong, 2022 ). This vaccine employs a strain of Salmonella that has undergone genetic modification to lower its severity, and it has been weakened to ensure safety.…”

Section: Introductionmentioning

confidence: 99%

“…In general, utilizing live attenuated vaccines appears to be a promising approach in the fight against antimicrobial resistance. The ongoing progress and innovation in this field will play a crucial role in combating AMR and fending off bacterial infections ( Micoli et al, 2021 ; Seo and Seong, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Crisis averted: a world united against the menace of multiple drug-resistant superbugs -pioneering anti-AMR vaccines, RNA interference, nanomedicine, CRISPR-based antimicrobials, bacteriophage therapies, and clinical artificial intelligence strategies to safeguard global antimicrobial arsenal

Saeed,

Insaf,

Piracha

et al. 2023

Front. Microbiol.

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The efficacy of antibiotics and other antimicrobial agents in combating bacterial infections faces a grave peril in the form of antimicrobial resistance (AMR), an exceedingly pressing global health issue. The emergence and dissemination of drug-resistant bacteria can be attributed to the rampant overuse and misuse of antibiotics, leading to dire consequences such as organ failure and sepsis. Beyond the realm of individual health, the pervasive specter of AMR casts its ominous shadow upon the economy and society at large, resulting in protracted hospital stays, elevated medical expenditures, and diminished productivity, with particularly dire consequences for vulnerable populations. It is abundantly clear that addressing this ominous threat necessitates a concerted international endeavor encompassing the optimization of antibiotic deployment, the pursuit of novel antimicrobial compounds and therapeutic strategies, the enhancement of surveillance and monitoring of resistant bacterial strains, and the assurance of universal access to efficacious treatments. In the ongoing struggle against this encroaching menace, phage-based therapies, strategically tailored to combat AMR, offer a formidable line of defense. Furthermore, an alluring pathway forward for the development of vaccines lies in the utilization of virus-like particles (VLPs), which have demonstrated their remarkable capacity to elicit a robust immune response against bacterial infections. VLP-based vaccinations, characterized by their absence of genetic material and non-infectious nature, present a markedly safer and more stable alternative to conventional immunization protocols. Encouragingly, preclinical investigations have yielded promising results in the development of VLP vaccines targeting pivotal bacteria implicated in the AMR crisis, including Salmonella, Escherichia coli, and Clostridium difficile. Notwithstanding the undeniable potential of VLP vaccines, formidable challenges persist, including the identification of suitable bacterial markers for vaccination and the formidable prospect of bacterial pathogens evolving mechanisms to thwart the immune response. Nonetheless, the prospect of VLP-based vaccines holds great promise in the relentless fight against AMR, underscoring the need for sustained research and development endeavors. In the quest to marshal more potent defenses against AMR and to pave the way for visionary innovations, cutting-edge techniques that incorporate RNA interference, nanomedicine, and the integration of artificial intelligence are currently under rigorous scrutiny.

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Prospects on Repurposing a Live Attenuated Vaccine for the Control of Unrelated Infections

Cited by 11 publications

References 132 publications

Combination Therapy for the Treatment of Shingles with an Immunostimulatory Vaccine Virus and Acyclovir

Combination Therapy for the Treatment of Shingles with an Immunostimulatory Vaccine Virus and Acyclovir

Effect of Antigen Structure in Subunit Vaccine Nanoparticles on Humoral Immune Responses

Crisis averted: a world united against the menace of multiple drug-resistant superbugs -pioneering anti-AMR vaccines, RNA interference, nanomedicine, CRISPR-based antimicrobials, bacteriophage therapies, and clinical artificial intelligence strategies to safeguard global antimicrobial arsenal

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