Biology subjects

Fattom, A.

Publications and source records attributed to Fattom, A..

3 recordsLinked to original sources

bioRxiv2022

Enhancing Polysaccharide Immunity through Intranasal Immunizations

ObjectiveA model conjugate vaccine incorporating a pneumococcal polysaccharide with EcoCRM197 was used to determine vaccine efficacy when administered with our clinical-stage mucosal stimulating adjuvant, NE01. This was the first attempt at combining NE01 with a polysaccharide conjugate vaccine to elicit mucosal immunity against respiratory bacterial infection through intranasal immunizations. ResultsIntranasal immunizations using the NE01 adjuvant incorporating a polysaccharide conjugate resulted in the generation of a robust IgG and IgA responses in both serum and mucosa. Our data also demonstrated the active homing of immunological memory cells to the lower respiratory tract as evidenced by an increase of IgG- and IgA-producing memory B-cells in the lungs. Further, intranasal immunization enhanced the induction of a balanced Th1/Th2/ Th17 immune response with clear homing of memory T-cells to the lungs. Serum antibodies generated by this formulation and route of administration demonstrated excellent efficacy in killing S. pneumonia in an in vitro OPK assay, a biomarker of vaccine efficacy. Our data suggest that further optimization of the dose and schedule as well as evaluation of the efficacy of this new formulation in animal models of colonization and infection are warranted.

immunology↗

bioRxiv2022

Intranasal Nanoemulsion Adjuvanted S-2P Vaccine Demonstrates Protection in Hamsters and Induces Systemic, Cell-Mediated and Mucosal Immunity in Mice

With the rapid progress made in the development of vaccines to fight the SARS-CoV-2 pandemic, almost >90% of vaccine candidates under development and a 100% of the licensed vaccines are delivered intramuscularly (IM). While these vaccines are highly efficacious against COVID-19 disease, their efficacy against SARS-CoV-2 infection of upper respiratory tract and transmission is at best temporary. Development of safe and efficacious vaccines that are able to induce robust mucosal and systemic immune responses are needed to control new variants. In this study, we have used our nanoemulsion adjuvant (NE01) to intranasally (IN) deliver stabilized spike protein (S-2P) to induce immunogenicity in mouse and hamster models. Data presented demonstrate the induction of robust immunity in mice resulting in 100% seroconversion and protection against SARS-CoV-2 in a hamster challenge model. There was a significant induction of mucosal immune responses as demonstrated by IgA- and IgG-producing memory B cells in the lungs of animals that received intranasal immunizations compared to an alum adjuvanted intramuscular vaccine. The efficacy of the S-2P/NE01 vaccine was also demonstrated in an intranasal hamster challenge model with SARS-CoV-2 and conferred significant protection against weight loss, lung pathology, and viral clearance from both upper and lower respiratory tract. Our findings demonstrate that intranasal NE01-adjuvanted vaccine promotes protective immunity against SARS-CoV-2 infection and disease through activation of three arms of immune system: humoral, cellular, and mucosal, suggesting that an intranasal SARS-CoV-2 vaccine may play a role in addressing a unique public health problem and unmet medical need.

immunology↗

bioRxiv2022

Protection of Hamsters Challenged with SARS-CoV-2 after Two Doses of MVC-COV1901 Vaccine Followed by a Single Intranasal Booster with Nanoemulsion Adjuvanted S-2P Vaccine

Intramuscular vaccines have greatly reduced hospitalization and death due to severe COVID-19. However, most countries are experiencing a resurgence of infection driven predominantly by the Delta and Omicron variants of SARS-CoV-2. In response, booster dosing of COVID-19 vaccines has been implemented in many countries to address waning immunity and reduced protection against the variants. However, intramuscular boosting fails to elicit mucosal immunity and therefore does not solve the problem of persistent viral carriage and transmission, even in patients protected from severe disease. In this study, two doses of stabilized prefusion SARS-CoV-2 spike (S-2P)-based intramuscular vaccine adjuvanted with Alum/CpG1018, MVC-COV1901, were used as a primary vaccination series, followed by an intranasal booster vaccination with nanoemulsion (NE01)-adjuvanted S-2P vaccine in a hamster model to demonstrate immunogenicity and protection from viral challenge. Here we report that this vaccination regimen resulted not only in the induction of robust immunity and protection against weight loss and lung pathology following challenge with SARS-CoV-2, but also led to increased viral clearance from both upper and lower respiratory tracts. Our findings showed that intramuscular MVC-COV1901 vaccine followed by a booster with intranasal NE01-adjuvanted vaccine promotes protective immunity against both viral infection and disease, suggesting that this immunization protocol may offer a solution in addressing a significant, unmet medical need for both the COVID-19 and future pandemics.

immunology↗