The Long-Term Immunity of a Microneedle Array Patch of a SARS-CoV-2 S1 Protein Subunit Vaccine Irradiated by Gamma Rays in Mice

Vaccines, Год журнала: 2025, Номер 13(1), С. 86 - 86

Опубликована: Янв. 18, 2025

Background/Objectives: COVID-19 vaccines effectively prevent severe disease, but unequal distribution, especially in low- and middle-income countries, has led to vaccine-resistant strains. This highlights the urgent need for alternative vaccine platforms that are safe, thermostable, easy distribute. study evaluates immunogenicity, stability, scalability of a dissolved microneedle array patch (MAP) delivering rS1RS09 subunit vaccine, comprising SARS-CoV-2 S1 monomer RS09, TLR-4 agonist peptide. Methods: The was administered via MAP or intramuscular injection murine models. immune responses with without gamma irradiation as terminal sterilization were assessed at doses 5, 15, 45 µg, alongside neutralizing antibody Wuhan, Delta, Omicron variants. long-term storage stability also evaluated through protein degradation analyses varying temperatures. Results: elicited stronger ACE2-binding inhibition than alone trimer. delivery induced sgnificantly higher longer-lasting S1-specific IgG up 70 weeks compared injections. Robust Th2-prevalent generated all groups vaccinated significant antibodies 15 showing dose-sparing potential. remained stable minimal 19 months room temperature under refrigeration, regardless gamma-irradiation. After an additional month 42 °C, cit showed less 3% degradation, ompared over 23% liquid Conclusions: Gamma-irradiated MAP-rS1RS09 is promising platform stable, scalable production eliminating cold chain logistics. These findings support its potential mass vaccination efforts, particularly resource-limited settings.

Язык: Английский

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Fourth dose of microneedle array patch of SARS-CoV-2 S1 protein subunit vaccine elicits robust long-lasting humoral responses in mice

International Immunopharmacology, Год журнала: 2024, Номер 129, С. 111569 - 111569

Опубликована: Фев. 9, 2024

Язык: Английский

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Unveiling a Shield of Hope: A Novel Multiepitope-Based Immunogen for Cross-Serotype Cellular Defense against Dengue Virus

Vaccines, Год журнала: 2024, Номер 12(3), С. 316 - 316

Опубликована: Март 16, 2024

Dengue virus (DENV) infection continues to be a public health challenge, lacking specific cure. Vaccination remains the primary strategy against dengue; however, existing live-attenuated vaccines display variable efficacy across four serotypes, influenced by host serostatus and age, predominantly inducing humoral responses. To address this limitation, study investigates multiepitope-based immunogen designed induce robust cellular immunity all DENV serotypes. The chimeric integrates H-2d MHC-I binding T-cell epitopes derived from conserved domains within envelope protein. Immuno-informatics analyses supported its stability, non-allergenic nature, strong affinity as an antigen. assess immunogenicity of multiepitope, it was expressed in murine bone-marrow-derived dendritic cells (BMDCs) that were used prime mice. In experimental model, simultaneous exposure serotypes initiated distinct IFNγ-CD8 responses for different These results potential multiepitope construct vaccine candidate. While optimization design continuous pursuit, proof-of-concept provides starting point evaluating protective dengue vivo. Moreover, our support development could trigger pan-serotype anti-dengue CD8 response.

Язык: Английский

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Multivalent and Sequential Heterologous Spike Protein Vaccinations Effectively Induce Protective Humoral Immunity against SARS-CoV-2 Variants

Vaccines, Год журнала: 2024, Номер 12(4), С. 362 - 362

Опубликована: Март 27, 2024

The emergence of new SARS-CoV-2 variants continues to cause challenging problems for the effective control COVID-19. In this study, we tested hypothesis whether a strategy multivalent and sequential heterologous spike protein vaccinations would induce broader range higher levels neutralizing antibodies against more protection than homologous vaccination in mouse model. We determined spike-specific IgG, receptor-binding inhibition titers, protective efficacy groups mice that were vaccinated with recombinant proteins (Wuhan, Delta, Omicron), sequentially variants, or proteins. Trivalent (Wuhan + Delta Omicron) inducing serum activities receptor binding virus antibody titers vaccination. was observed trivalent after challenge mouse-adapted MA10 strain compared This study provides evidence variant might provide emerging significantly alleviate severe inflammation due

Язык: Английский

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Tetravalent SARS-CoV-2 S1 subunit protein vaccination elicits robust humoral and cellular immune responses in SIV-infected rhesus macaque controllers

mBio, Год журнала: 2023, Номер 14(5)

Опубликована: Окт. 13, 2023

ABSTRACT The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need for safe and effective vaccines to be rapidly developed distributed worldwide, especially considering emergence of new severe acute respiratory syndrome 2 (SARS-CoV-2) variants. Protein subunit have emerged as a promising approach due their proven safety record ability elicit robust immune responses. In this study, we evaluated immunogenicity efficacy an adjuvanted tetravalent S1 protein COVID-19 vaccine candidate composed Wuhan, B.1.1.7 variant, B.1.351 P.1 variant spike proteins in nonhuman primate model with controlled SIVsab infection. induced both humoral cellular responses, T B cell responses mainly peaking post boost immunization. also elicited neutralizing cross-reactive antibodies, angiotensin-converting enzyme (ACE2)-blocking including spike-specific CD4 + cells. Importantly, was able generate Omicron spike-binding ACE2-blocking antibodies without specifically vaccinating Omicron, suggesting potential broad protection against emerging composition significant implications development implementation, providing antibody numerous SARS-CoV-2 IMPORTANCE study provides important insights into (SARS-CoV-2). primates SIVagm infection variant-specific Omicron. These findings suggest that could provide multiple variants while minimizing risk escape Additionally, use rhesus macaques may better represent humans chronic viral diseases, highlighting importance preclinical animal models development. Overall, valuable information implementation vaccines, particularly achieving global equity addressing

Язык: Английский

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Second Boost of Omicron SARS-CoV-2 S1 Subunit Vaccine Induced Broad Humoral Immune Responses in Elderly Mice

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 6, 2024

Currently approved COVID-19 vaccines prevent symptomatic infection, hospitalization, and death from the disease. However, repeated homologous boosters, while considered a solution for severe forms of disease caused by new SARS-CoV-2 variants in elderly individuals immunocompromised patients, cannot provide complete protection against breakthrough infections. This highlights need alternative platforms booster vaccines. In our previous study, we assessed boost effect Beta S1 recombinant protein subunit vaccine (rS1Beta) aged mice primed with an adenovirus-based expressing SARS-CoV-2-S1 (Ad5.S1) via subcutaneous injection or intranasal delivery, which induced robust humoral immune responses (1). this follow-up demonstrated that second dose non-adjuvanted Omicron (BA.1) Toll-like receptor 4 (TLR4) agonist RS09 (rS1RS09OM) was effective stimulating strong S1-specific inducing significantly high neutralizing antibodies Wuhan, Delta, 100-week-old mice. Importantly, elicits cross-reactive antibody responses, resulting ACE2 binding inhibition spike variants, including its subvariants. Interestingly, levels IgG correlated level serum samples, although showed weaker correlation compared to Wuhan level. Furthermore, immunogenic properties rS1 young, middle-aged, mice, reduced immunogenicity age, especially impaired Th1-biased response Our findings demonstrate variant concern (VOC) as has potential offer cross-neutralization broad range improve effectiveness newly emerging who were previously authorized

Язык: Английский

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The Development of Epitope-Based Recombinant Protein Vaccines against SARS-CoV-2

The AAPS Journal, Год журнала: 2024, Номер 26(5)

Опубликована: Авг. 13, 2024

Язык: Английский

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Long-term Immunity of a Microneedle Array Patch of SARS-CoV-2 S1 Protein Subunit Vaccine Irradiated by Gamma Rays in Mice

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 25, 2024

Abstract COVID-19 vaccines effectively prevent symptomatic infection and severe disease, including hospitalization death. However, unequal vaccine distribution during the pandemic, especially in low- middle-income countries, has led to emergence of vaccine-resistant strains. This underscores need for alternative, safe, thermostable platforms, such as dissolved microneedle array patches (MAP) delivering a subunit vaccine, which eliminate cold chain trained healthcare personnel. study demonstrates that SARS-CoV-2 S1 monomer with RS09, TLR-4 agonist peptide, serves an optimal protein immunogen. combination stimulates stronger S1-specific immune response, resulting binding membrane-bound spike on cell surface ACE2-binding inhibition, compared alone or trimer S1, regardless RS09. MAP delivery rS1RS09 elicited higher longer-lasting immunity conventional intramuscular injection. IgG levels remained significantly elevated up 70 weeks post-administration. Additionally, different doses 5, 15, 45 μ g induced robust sustained Th2-prevalent responses, suggesting dose-sparing effect inducing high neutralizing antibodies against Wuhan, Delta, Omicron variants at 15 dose. Moreover, gamma irradiation terminal sterilization method did not affect immunogenicity, irradiated maintaining comparable efficacy non-irradiated ones. The stability was evaluated after long-term storage room temperature refrigeration 19 months, showing minimal degradation. Further, additional one-month (42°C), both degraded less than 3%, while liquid over 23%. Overall, these results indicate sterilized MAP-rS1RS09 maintain extended without refrigeration, supporting their potential mass production widespread use global vaccination efforts.

Язык: Английский

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Tetravalent SARS-CoV-2 S1 Subunit Protein Vaccination Elicits Robust Humoral and Cellular Immune Responses in SIV-Infected Rhesus Macaque Controllers

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Март 16, 2023

The COVID-19 pandemic has highlighted the need for safe and effective vaccines to be rapidly developed distributed worldwide, especially considering emergence of new SARS-CoV-2 variants. Protein subunit have emerged as a promising approach due their proven safety record ability elicit robust immune responses. In this study, we evaluated immunogenicity efficacy an adjuvanted tetravalent S1 protein vaccine candidate composed Wuhan, B.1.1.7 variant, B.1.351 P.1 variant spike proteins in nonhuman primate model with controlled SIVsab infection. induced both humoral cellular responses, T- B cell responses mainly peaking post-boost immunization. also elicited neutralizing cross-reactive antibodies, ACE2 blocking T-cell including specific CD4+ T cells. Importantly, was able generate Omicron binding antibodies without specifically vaccinating Omicron, suggesting potential broad protection against emerging composition significant implications development implementation, providing antibody numerous

Язык: Английский

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Fourth dose of Microneedle Array Patch of SARS-CoV-2 S1 Protein Subunit Vaccine Elicits Robust Long-lasting Humoral Responses in mice

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Окт. 5, 2023

Abstract The COVID-19 pandemic has underscored the pressing need for safe and effective booster vaccines, particularly in considering emergence of new SARS-CoV-2 variants addressing vaccine distribution inequalities. Dissolving microneedle array patches (MAP) offer a promising delivery method, enhancing immunogenicity improving accessibility through skin’s immune potential. In this study, we evaluated patch-based S1 subunit protein candidate, which comprised bivalent formulation targeting Wuhan Beta variant alongside monovalent Delta spike proteins murine model. Notably, second boost homologous MAP-S1(WU+Beta) induced 15.7-fold increase IgG endpoint titer, while third heterologous MAP-S1RS09Delta yielded more modest 1.6-fold increase. Importantly, study demonstrated that administration four doses MAP robust long-lasting responses, persisting at least 80 weeks. These responses encompassed various isotypes remained statistically significant one year. Furthermore, neutralizing antibodies against multiple were generated, with comparable observed Omicron variant. Overall, these findings emphasize potential MAP-based vaccines as strategy to combat evolving landscape deliver worldwide.

Язык: Английский

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