Can the Nasal Cavity Help Tackle COVID-19?

Pilicheva, Bissera; Boyuklieva, Radka

doi:10.3390/pharmaceutics13101612

Cited by 20 publications

(20 citation statements)

References 124 publications

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“…Viral vectors are attractive as they can be engineered to incorporate genes encoding diverse antigens and result in high transfection efficiency. However, viral vectors can be limited by scalability issues, safety concerns, heterogeneous antigen expression and pre-existing immunity ( 43 ). Subunit vaccines are generally safer although poorly immunogenic.…”

Section: Discussionmentioning

confidence: 99%

Intranasal Delivery of Thermostable Subunit Vaccine for Cross-Reactive Mucosal and Systemic Antibody Responses Against SARS-CoV-2

et al. 2022

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Despite the remarkable efficacy of currently approved COVID-19 vaccines, there are several opportunities for continued vaccine development against SARS-CoV-2 and future lethal respiratory viruses. In particular, restricted vaccine access and hesitancy have limited immunization rates. In addition, current vaccines are unable to prevent breakthrough infections, leading to prolonged virus circulation. To improve access, a subunit vaccine with enhanced thermostability was designed to eliminate the need for an ultra-cold chain. The exclusion of infectious and genetic materials from this vaccine may also help reduce vaccine hesitancy. In an effort to prevent breakthrough infections, intranasal immunization to induce mucosal immunity was explored. A prototype vaccine comprised of receptor-binding domain (RBD) polypeptides formulated with additional immunoadjuvants in a chitosan (CS) solution induced high levels of RBD-specific antibodies in laboratory mice after 1 or 2 immunizations. Antibody responses were durable with high titers persisting for at least five months following subcutaneous vaccination. Serum anti-RBD antibodies contained both IgG1 and IgG2a isotypes suggesting that the vaccine induced a mixed Th1/Th2 response. RBD vaccination without CS formulation resulted in minimal anti-RBD responses. The addition of CpG oligonucleotides to the CS plus RBD vaccine formulation increased antibody titers more effectively than interleukin-12 (IL-12). Importantly, generated antibodies were cross-reactive against RBD mutants associated with SARS-CoV-2 variants of concern, including alpha, beta and delta variants, and inhibited binding of RBD to its cognate receptor angiotensin converting enzyme 2 (ACE2). With respect to stability, vaccines did not lose activity when stored at either room temperature (21-22°C) or 4°C for at least one month. When delivered intranasally, vaccines induced RBD-specific mucosal IgA antibodies, which may protect against breakthrough infections in the upper respiratory tract. Altogether, data indicate that the designed vaccine platform is versatile, adaptable and capable of overcoming key constraints of current COVID-19 vaccines.

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Section: Discussionmentioning

confidence: 99%

Intranasal Delivery of Thermostable Subunit Vaccine for Cross-Reactive Mucosal and Systemic Antibody Responses Against SARS-CoV-2

et al. 2022

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“…Nasal sprays to combat SARS Cov-2 have been proposed, including nasal administration of nitric oxide (NO) (25), carrageenan, Ivermectin, chloroquine, Niclosamide, steroids, ethyl lauroyl arginate, hypochlorous acid, povidone-iodine, antibodies, lipopeptide, and a PEGylated TLR2/6 agonist. All are in various levels of pre-clinical or clinical trials (26).…”

Section: Discussionmentioning

confidence: 99%

In VitroActivity of Cysteamine Against SARS-CoV-2 Variants

Thoene

Gavin²,

Towne

et al. 2021

Preprint

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Global COVID-19 pandemic is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Continuous emergence of new variants and their rapid spread are jeopardizing vaccine countermeasures to a significant extent. While currently available vaccines are effective at preventing illness associated with SARS-CoV-2 infection, these have been shown to be less effective at preventing breakthrough infection and transmission from a vaccinated individual to others. Here we demonstrate broad antiviral activity of cysteamine HCl in vitro against variants of SARS-CoV-2 assayed in a highly permissible Vero cell line. Cysteamine HCl inhibited infection of alpha, beta, gamma and delta variants effectively and the inhibitory activity was shown to manifest during the early stages of viral infection. Cysteamine is a very well-tolerated US FDA-approved drug used chronically as a topical ophthalmic solution to treat ocular cystinosis in patients who receive it hourly or QID lifelong at concentrations 3 to 4 times higher than that required to inhibit SARS CoV-2 in tissue culture. Application of cysteamine as a topical nasal treatment can potentially : 1) mitigate existing infection 2) prevent infection in exposed individuals, and 3) limit the contagion in vulnerable populations.

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“…At the preclinical stage, significant protection has also been reported in animal models using IN administration of antibodies to SARS-CoV-2 (see Table 9 ). Included in this group are antibody-based products such as EU126-M2 [ 501 , 502 ] and the Nb15-NbH-Nb15 bispecific nanobody derived from llamas [ 503 ], each of which has reported significant protection in mouse models of SARS-CoV-2 infection. Similarly, a trimeric nanobody has been reported that can potently neutralize SARS-CoV-2, and that may be useful for intranasal delivery [ 346 ].…”

Section: Alternative Modes Of Deliverymentioning

confidence: 99%

Passive Immunotherapy Against SARS-CoV-2: From Plasma-Based Therapy to Single Potent Antibodies in the Race to Stay Ahead of the Variants

Strohl

et al. 2022

BioDrugs

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The COVID-19 pandemic is now approaching 2 years old, with more than 440 million people infected and nearly six million dead worldwide, making it the most significant pandemic since the 1918 influenza pandemic. The severity and significance of SARS-CoV-2 was recognized immediately upon discovery, leading to innumerable companies and institutes designing and generating vaccines and therapeutic antibodies literally as soon as recombinant SARS-CoV-2 spike protein sequence was available. Within months of the pandemic start, several antibodies had been generated, tested, and moved into clinical trials, including Eli Lilly’s bamlanivimab and etesevimab, Regeneron’s mixture of imdevimab and casirivimab, Vir’s sotrovimab, Celltrion’s regdanvimab, and Lilly’s bebtelovimab. These antibodies all have now received at least Emergency Use Authorizations (EUAs) and some have received full approval in select countries. To date, more than three dozen antibodies or antibody combinations have been forwarded into clinical trials. These antibodies to SARS-CoV-2 all target the receptor-binding domain (RBD), with some blocking the ability of the RBD to bind human ACE2, while others bind core regions of the RBD to modulate spike stability or ability to fuse to host cell membranes. While these antibodies were being discovered and developed, new variants of SARS-CoV-2 have cropped up in real time, altering the antibody landscape on a moving basis. Over the past year, the search has widened to find antibodies capable of neutralizing the wide array of variants that have arisen, including Alpha, Beta, Gamma, Delta, and Omicron. The recent rise and dominance of the Omicron family of variants, including the rather disparate BA.1 and BA.2 variants, demonstrate the need to continue to find new approaches to neutralize the rapidly evolving SARS-CoV-2 virus. This review highlights both convalescent plasma- and polyclonal antibody-based approaches as well as the top approximately 50 antibodies to SARS-CoV-2, their epitopes, their ability to bind to SARS-CoV-2 variants, and how they are delivered. New approaches to antibody constructs, including single domain antibodies, bispecific antibodies, IgA- and IgM-based antibodies, and modified ACE2-Fc fusion proteins, are also described. Finally, antibodies being developed for palliative care of COVID-19 disease, including the ramifications of cytokine release syndrome (CRS) and acute respiratory distress syndrome (ARDS), are described. Supplementary Information The online version contains supplementary material available at 10.1007/s40259-022-00529-7.

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Can the Nasal Cavity Help Tackle COVID-19?

Cited by 20 publications

References 124 publications

Intranasal Delivery of Thermostable Subunit Vaccine for Cross-Reactive Mucosal and Systemic Antibody Responses Against SARS-CoV-2

Intranasal Delivery of Thermostable Subunit Vaccine for Cross-Reactive Mucosal and Systemic Antibody Responses Against SARS-CoV-2

In VitroActivity of Cysteamine Against SARS-CoV-2 Variants

Passive Immunotherapy Against SARS-CoV-2: From Plasma-Based Therapy to Single Potent Antibodies in the Race to Stay Ahead of the Variants

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