Pagano, Pasqualina (2023) A novel strategy for the identification of genetic adjuvants for adenovirus vectored vaccines against infectious diseases and cancer. [Tesi di dottorato]
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| Tipologia del documento: | Tesi di dottorato |
|---|---|
| Lingua: | English |
| Titolo: | A novel strategy for the identification of genetic adjuvants for adenovirus vectored vaccines against infectious diseases and cancer |
| Autori: | Autore Email Pagano, Pasqualina pasqualina.pagano2@unina.it |
| Data: | 10 Marzo 2023 |
| Numero di pagine: | 64 |
| Istituzione: | Università degli Studi di Napoli Federico II |
| Dipartimento: | Medicina Molecolare e Biotecnologie Mediche |
| Dottorato: | Medicina molecolare e biotecnologie mediche |
| Ciclo di dottorato: | 35 |
| Coordinatore del Corso di dottorato: | nome email Santoro, Massimo masantor@unina.it |
| Tutor: | nome email Nicosia, Alfredo [non definito] |
| Data: | 10 Marzo 2023 |
| Numero di pagine: | 64 |
| Parole chiave: | Genetic vaccines; adjuvant; adenovirus; immunomodulators; infectious diseases; cancer |
| Settori scientifico-disciplinari del MIUR: | Area 05 - Scienze biologiche > BIO/11 - Biologia molecolare |
| Depositato il: | 21 Mar 2023 10:35 |
| Ultima modifica: | 10 Apr 2025 12:41 |
| URI: | http://www.fedoa.unina.it/id/eprint/15081 |
Abstract
Genetic vaccines have been implemented showing a number of advantages over conventional vaccine platforms such as the ability to induce both humoral and cellular immunity. This notwithstanding, genetic vaccine technologies are still amenable to improvement of their potency and durability of the induced immunity. Most of the known adjuvants (Alum, MF59, ASO4 etc.) co-administered boost adaptive immune responses by activating the innate immune system. However, in the case of genetic vaccines, these adjuvants may inhibit the in vivo expression of the encoded antigen thus hampering vaccination efficacy. The aim of the current project is to validate the approach of encoding immunomodulators in Adenovirus vectors to be used as genetic vaccine adjuvants, and to identify novel Adenovirus-encoded molecules capable of improving the extent and the durability of the immune responses induced by Adenovirus vectored vaccines. From a preliminary experiment, which demonstrated the adjuvant effect of an Adenovirus vector encoding an immunomodulatory antibody (anti-CTLA4) on anti-infectious and anti-cancer Adenovirus-based vaccines, we extended the genetic adjuvant approach to encode immunomodulatory molecules such cytokines, chemokines and other protein factors (IMs) other than antibodies We therefore generated tools and set up protocols for the generation of a library of Adenovirus encoded immunomodulators (Ad-IMs). We then generated ten Ad-IMs and tested five of them for their adjuvant activity. The results of this work showed that the approach is feasible and can lead to the identification of novel Adenovirus vectored immunomodulators with significant adjuvant activity.
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