Screening Optimal Vaccine Adjuvants for Recombinant Protein-Based Coronavirus Vaccine
Lehto, Heini (2024-05-08)
Screening Optimal Vaccine Adjuvants for Recombinant Protein-Based Coronavirus Vaccine
Lehto, Heini
(08.05.2024)
Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty.
suljettu
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2024060747995
https://urn.fi/URN:NBN:fi-fe2024060747995
Tiivistelmä
To fully prevent respiratory diseases like COVID-19, vaccines need to activate mucosal immune responses. Yet, all current COVID-19 vaccines are administered intramuscularly, which, while effective at generating high levels of antibodies against systemic viral infections, does not induce mucosal immune response. In contrast, administration through mucosal routes can promote both mucosal and systemic immune responses. An intranasally administered protein-based coronavirus vaccine, with the right adjuvant enhancing both humoral and cellular immune responses, could solve the persistent global problem.
This study aimed to identify the optimal vaccine adjuvant for novel recombinant protein-based coronavirus vaccine. Currently, no mucosal adjuvants are used with licensed vaccines and therefore several experimental adjuvants were screened in a mouse model to assess their ability to enhance humoral and cellular immune responses.
Female BALB/c mice were immunised three times with a four-week interval. The first dose was administered intramuscularly, and the following two doses were administered intranasally. Serum samples were collected throughout the study. Upon sacrification on week twelve whole blood, spleen and bronchoalveolar lavage samples were collected. The humoral immune response was analysed with antigen-specific ELISA and the cellular immune response was analysed with FluoroSpot assay to determine the induced cytokine levels.
As a result, Adjuvant X was identified as the most promising adjuvant candidate. It induced robust and balanced humoral and cellular immune response against vaccine antigens as well as elicited good mucosal response. Incorporation of branched polyethyleneimine (BPEI) compound as a second adjuvant with Adjuvant X in the vaccine formulation further improved the mucosal immune responses but had no substantial effect on humoral or cellular immune responses. Following these findings, the next step in our research is to conduct microneutralization assay to provide insights into whether this vaccine adjuvant combination, particularly the incorporation of BPEI alongside Adjuvant X, is capable of eliciting neutralizing antibodies.
This study aimed to identify the optimal vaccine adjuvant for novel recombinant protein-based coronavirus vaccine. Currently, no mucosal adjuvants are used with licensed vaccines and therefore several experimental adjuvants were screened in a mouse model to assess their ability to enhance humoral and cellular immune responses.
Female BALB/c mice were immunised three times with a four-week interval. The first dose was administered intramuscularly, and the following two doses were administered intranasally. Serum samples were collected throughout the study. Upon sacrification on week twelve whole blood, spleen and bronchoalveolar lavage samples were collected. The humoral immune response was analysed with antigen-specific ELISA and the cellular immune response was analysed with FluoroSpot assay to determine the induced cytokine levels.
As a result, Adjuvant X was identified as the most promising adjuvant candidate. It induced robust and balanced humoral and cellular immune response against vaccine antigens as well as elicited good mucosal response. Incorporation of branched polyethyleneimine (BPEI) compound as a second adjuvant with Adjuvant X in the vaccine formulation further improved the mucosal immune responses but had no substantial effect on humoral or cellular immune responses. Following these findings, the next step in our research is to conduct microneutralization assay to provide insights into whether this vaccine adjuvant combination, particularly the incorporation of BPEI alongside Adjuvant X, is capable of eliciting neutralizing antibodies.