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Emerging Nanotechnology-Enabled Approaches to Mitigate COVID-19 Pandemic
Published in Devarajan Thangadurai, Saher Islam, Charles Oluwaseun Adetunji, Viral and Antiviral Nanomaterials, 2022
Maria Shoukat, Samiullah Khan, Arshad Islam, Maleeha Azam, Malik Badshah
This nano-based approach has been examined by Epivax, aiming to produce a cocktail vaccine to provide protection against COVID-19 (Epivax 2020). Another nanotechnology-based vaccine candidate developed by Nanovax Company is presently in phase 3 clinical trial (NCT04368988). It is formulated by using full-length S protein of SARS-CoV-2 in combination with saponin-based Matrix-M™ adjuvant to stimulate the entrance of APCs into the vaccine injected site, thus increasing the immunological response by presenting the antigen in targeted sites, such as local lymph nodes (Magnusson et al. 2018). Currently, 16 more nano-based VLP vaccine candidates against SARS-CoV-2 have been developed and are under preclinical phase (WHO 2020b). Table 13.3 depicts the recently developed and under trial VLPs as vaccine candidates against SARS-CoV-2.
Nanomaterials in COVID-19 Drug Development
Published in Debmalya Barh, Kenneth Lundstrom, COVID-19, 2022
Alaa A. A. Aljabali, Ángel Serrano-Aroca, Kenneth Lundstrom, Murtaza M. Tambuwala
The full-length or specific regions of the SARS-CoV-2 S protein have been targeted for vaccine development. For example, the receptor-binding domain (RBD) and the N-terminal sequence encoding a CD5 signal sequence, enhanced humoral and cellular immune response. In phase I/II clinical trials, Novavax NVX-CoV2373, the full-length SARS-CoV-2 S protein in combination with the saponin-based Matrix-M adjuvant, showed a good safety profile and elicited superior immune responses compared to levels detected in convalescent COVID-19 patients (NCT04368988) [45]. Furthermore, the NVX-CoV2373 vaccine demonstrated an efficacy of 86% against the SARS-CoV-2 B.1.1.7 UK variant and 60% against the B.1.351 South African variant in phase II trials [46]. Nanoparticles act in a similar way to viruses and can be used for delivery of cargo to a particular target. The application of nanoparticles can enhance immune responses of vaccines due to cell membrane penetration and subcellular targeting. Various materials such as lipids, polymers, and polysaccharides may be used for the formulation of nanocarriers. For example, lipid nanoparticle encapsulation can protect DNA or RNA from enzymatic degradation leading to an improved immune response to nanomaterial-based vaccines.
Single Particle Motion
Published in Rob Appleby, Graeme Burt, James Clarke, Hywel Owen, The Science and Technology of Particle Accelerators, 2020
Rob Appleby, Graeme Burt, James Clarke, Hywel Owen
We shall state this without proof. Similarity transforms come from matrix theory and lead to all manner of nice properties such as identical eigenvalues and traces before and after the transformation. Let's be concrete and denote the matrix M (from s to s′) by
Malaria vaccines in the eradication era: current status and future perspectives
Published in Expert Review of Vaccines, 2019
K. L. Wilson, K. L. Flanagan, M. D. Prakash, M. Plebanski
Combining adjuvants with current vaccines is likely needed to enhance immune responses and therefore vaccine efficacy. ChAd63-MVA ME-TRAP was recently trialled with the saponin based adjuvant Matrix-M (mixed matrix particles from saponin fractions [51]). The inclusion of Matrix M was well tolerated, with no increase in local reactogenicity, but some increased reporting of mild adverse events (AEs). However, there was no substantial benefit on either cellular or humoral immunogenicity with the addition of adjuvant [52]. Interestingly, in a CHMI model in healthy malaria naïve adults, combining the ChAd63-MVA ME-TRAP regimen (a known potent T cell inducer) sequentially with RTS, S/AS01 (high level antibody inducer) increased protection to 82.4% (14/17 individuals protected), compared to 75% (12/16) protection with RTS, S/AS01 alone [53]. This difference was not statistically significant, possibly due to a low study power. The ChAd-MVA approach is unlikely to replace RTS, S given its lack of superiority, but may be a good option for combination vaccine therapy for optimal T cell induction. Both vaccines in combination were well tolerated and both induced immune responses; and upon rechallenge 6 months later, 87.5% (7/8) in the combined vaccine group and 83.3% (5/6) RTS, S vaccinated individuals remained protected [53]. Results from combining vaccine regimens with different immunological strengths are encouraging, especially for subunit vaccines.
Pharmaceutical Aspects and Clinical Evaluation of COVID-19 Vaccines
Published in Immunological Investigations, 2021
Kirk Hofman, Gautam N. Shenoy, Vincent Chak, Sathy V. Balu-Iyer
For subunit vaccines, preclinical studies have demonstrated that the antigen alone (soluble antigen) does not induce a substantial immune response compared to those with adjuvant. It must be packaged into a nanoparticle for efficient uptake into cells and proteolytic processing in order to mount a robust adaptive immune response. Classical adjuvants such as alum are under investigation, and although its mechanism is not fully understood, it is thought to create an emulsion retaining the antigen at the injection site allowing for increased antigen uptake by APCs and presentation to T cells (Brewer 2006). As mentioned for mRNA-1273, although ALUM can boost the immune response, it may tend to follow a Th2 phenotype therefore other adjuvants are being investigated (Corbett et al. 2020). Matrix-M1, a saponin-based adjuvant is being employed by Novavax for their full length, Sf9 derived, recombinant spike protein vaccine (Keech et al. 2020). Their vaccine has shown protection from upper or lower respiratory infection upon challenge in non-human primates via induction of neutralizing antibodies in a Th1 dependent manner (Tian et al. 2020a). Matrix-M adjuvant has been used in development of influenza vaccines with an acceptable safety profile in clinical trials (Cox et al. 2011). Clover Pharmaceuticals has partnered with GSK and Dynavax in order to utilize their proprietary adjuvants AS03 and CpG 1018. AS03, developed by GSK, is included in licensed H5N1 pre-pandemic and H1N1 pandemic influenza vaccines (Garcon et al. 2012). AS03, composed of α-Tocopherol and squalene in an oil-in-water emulsion, induced greater antibody levels as well as CD4 + T cell responses toward H1N1 in human subjects compared to vaccine without adjuvant (Roman et al. 2011).
Nonhuman primate models for evaluation of SARS-CoV-2 vaccines
Published in Expert Review of Vaccines, 2022
Jessica A. Neil, Maryanne Griffith, Dale I. Godfrey, Damian F. J. Purcell, Georgia Deliyannis, David Jackson, Steve Rockman, Kanta Subbarao, Terry Nolan
The Novavax stabilized-S subunit adjuvanted vaccine (NVX-CoV2373) was assessed in cynomolgus macaques older than 3 years of age [75]. Animals received two doses of vaccine administered with Matrix-M adjuvant, a novel saponin-based adjuvant that was previously shown to improve the efficacy of protein-based vaccines for Influenza and Ebola in animal models [76,77]. Limited studies of this adjuvant had previously been completed in humans [78]. With the NVX-CoV2373 vaccine, studies in mice indicated that Matrix-M provides a 10-fold increase in antibody production, promotes Th1 cytokine responses, and provides protection against virus challenge [79]. A similar enhancement of antibody titers and Th1 cytokines responses was observed with Matrix-M adjuvant in baboons [79]. Following vaccination of the cynomolgus macaques, animals were challenged with SARS-CoV-2 (2019-nCoV/USA-WA1/2020). Neutralizing antibody titers developed in all animals at levels of 7.9–10.1 times that of human convalescent sera [75]. sgRNA was detected in the BAL of all control animals at day 2 post-challenge but was not detected in animals that received at least 5 µg of vaccine. Although virus was not detected in the nasal cavity of any of the vaccinated animals, it was also not detected in most control animals. Lung pathology ranged from moderate to severe in control animals with little inflammation observed in vaccinated animals. An additional study in rhesus macaques showed that a two-dose regimen was required for complete protection from infection and suggested that the NVX-CoV2373 vaccine can elicit functional antibodies against emerging SARS-CoV-2 variants [80]. In a phase I/II clinical trial, 5 and 25 µg doses with or without Matrix-M adjuvant were assessed for safety and immunogenicity [81]. While the safety profiles of both dose levels were acceptable in all groups, immunogenicity as assessed by antibody levels and Th1-cytokine production was enhanced in groups that received the adjuvanted vaccine and was consistent with the preclinical data. Overall, a two-dose regime with adjuvanted vaccine produced antibody titers 100-fold higher than unadjuvanted vaccine and approximately four-fold higher than convalescent sera. Phase III trials have shown an efficacy rate in UK cohorts of 86.3% against the Alpha variant and 96.4% against the ancestral strain [82]. In Mexico, vaccine efficacy against any variant was 92.6% [83]. In South Africa, efficacy against the Beta variant was 51% [84]. The Novavax vaccine is now approved for use in 36 countries, but to date there are no observational studies of efficacy. A recent press release from Novavax indicated that an Omicron-specific vaccine is in development (Novavax, https://www.novavax.com/science-technology/vaccine-pipeline/covid-19-omicron-vaccine).