Heterologous prime-boost: breaking the protective immune response bottleneck of COVID-19 vaccine candidates.
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ABSTRACT:
SUBMITTER: He Q
PROVIDER: S-EPMC8009122 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:New cancer vaccine strategies are required to vanquish the self-tolerance and elicit robust immune responses against tumor-associated antigens and/or neoantigens. Contemporary approaches in nanomedicine center on the use of a single nanocarrier modified with multiple copies of multiple different functional domains, e.g., epitopes for vaccines. Therefore, we set out to develop a combinatorial approach toward the next-generation concept of epitope delivery: a prime-boost strategy in which the same epitope is delivered using different nanocarriers. We tested this concept in the setting of HER2+ breast cancer. We synthesized HER2-based cancer vaccines using three icosahedral plant viruses as carriers and evaluated the immune response as a result of repetitive, homologous immunization using BALB/c mice. Two of the vaccines induced a Th2-predominant response and the other a Th1-predominant response. To enhance the immunogenicity of the vaccines, we developed a heterologous prime-boost strategy with each of the vaccines administered only once, yielding higher titers of HER2-specific immunoglobulins and increasing the toxicity of the antisera toward cancer cells. The prime-boost also induced a Th1-predominant response. An in vivo tumor challenge showed that the prime-boost regimen reduced tumor growth and improved survival in mice. This novel strategy to elicit robust immune responses against weakly immunogenic antigens in principle could be broadly applicable to cancers and other diseases.
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Project description:Three commercial vaccines are administered in domestic livestock farms for routine vaccination to aid for foot-and-mouth disease (FMD) control in Korea. Each vaccine contains distinct combinations of inactivated serotype O and A FMD virus (FMDV) antigens: O/Manisa + O/3039 + A/Iraq formulated in a double oil emulsion (DOE), O/Primorsky + A/Zabaikalsky formulated in a DOE, and O/Campos + A/Cruzeiro + A/2001 formulated in a single oil emulsion. Despite the recommendation for a prime-boost vaccination with the same vaccine in fattening pigs, occasional cross-inoculation is inevitable for many reasons, such as lack of compliance with vaccination guidelines, erroneous application, or change in vaccine types by suppliers. Therefore, there have been concerns that a poor immune response could be induced by cross-inoculation due to a failure to boost the immune response. In the present study, it was demonstrated by virus neutralization and ELISA tests that cross-inoculation of pigs with three commercial FMD vaccines does not hamper the immune response against the primary vaccine strains and enhances broader cross-reactivity against heterologous vaccine antigens whether they were applied or not. Therefore, it could be concluded that the cross-inoculation of FMD vaccines can be used as a regimen to strategically overcome the limitation of the antigenic spectrum induced by the original regimen.
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Project description:BackgroundThe objective of the present work was to assess the reactogenicity and immunogenicity of heterologous COVID-19 vaccination regimens in clinical trials and observational studies.MethodsPubMed, Cochrane Library, Embase, MedRxiv, BioRxiv databases were searched in September 29, 2021. The PRISMA instruction for systemic review was followed. Two reviewers independently selected the studies, extracted the data and assessed risk of bias. The quality of studies was evaluated using the New Castle-Ottawa and Cochrane risk of instrument. The characteristics and study outcome (e.g., adverse events, immune response, and variant of concern) were extracted.ResultsNineteen studies were included in the final data synthesis with 5 clinical trials and 14 observational studies. Heterologous vaccine administration showed a trend toward more frequent systemic reactions. However, the total reactogenicity was tolerable and manageable. Importantly, the heterologous prime-boost vaccination regimens provided higher immunogenic effect either vector/ mRNA-based vaccine or vector/ inactivated vaccine in both humoral and cellular immune response. Notably, the heterologous regimens induced the potential protection against the variant of concern, even to the Delta variant.ConclusionsThe current findings provided evidence about the higher induction of robust immunogenicity and tolerated reactogenicity of heterologous vaccination regimens (vector-based/mRNA vaccine or vector-based/inactivated vaccine). Also, this study supports the application of heterologous regimens against COVID-19 which may provide more opportunities to speed up the global vaccination campaign and maximize the capacity to control the pandemic.
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Project description:Several effective SARS-CoV-2 vaccines are currently in use, but effective boosters are needed to maintain or increase immunity due to waning responses and the emergence of novel variants. Here we report that intranasal vaccinations with adenovirus 5 and 19a vectored vaccines following a systemic plasmid DNA or mRNA priming result in systemic and mucosal immunity in mice. In contrast to two intramuscular applications of an mRNA vaccine, intranasal boosts with adenoviral vectors induce high levels of mucosal IgA and lung-resident memory T cells (TRM); mucosal neutralization of virus variants of concern is also enhanced. The mRNA prime provokes a comprehensive T cell response consisting of circulating and lung TRM after the boost, while the plasmid DNA prime induces mostly mucosal T cells. Concomitantly, the intranasal boost strategies lead to complete protection against a SARS-CoV-2 infection in mice. Our data thus suggest that mucosal booster immunizations after mRNA priming is a promising approach to establish mucosal immunity in addition to systemic responses.
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