Prospects of Replication-Deficient Adenovirus Based Vaccine Development against SARS-CoV-2

Garofalo, Mariangela; Staniszewska, Monika; Salmaso, Stefano; Caliceti, Paolo; Pancer, Katarzyna; Wieczorek, Magdalena; Kuryk, Łukasz

doi:10.3390/vaccines8020293

Cited by 16 publications

(13 citation statements)

References 66 publications

(104 reference statements)

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“…To date, more than 100 human AdV (HAdV) types have been isolated, characterized, and classified into seven species (A to G) (2). In addition to causing serious diseases in humans, several AdVs are being explored as vaccine vehicles against infectious diseases such as coronavirus disease 2019, Middle East respiratory syndrome (MERS), Ebola disease, AIDS, Lassa fever, and Zika disease (3). These efforts include a vaccine candidate based on HAdV-F41 that elicits neutralizing antibodies against MERS coronavirus in vivo (4).…”

Section: Introductionmentioning

confidence: 99%

The structure of enteric human adenovirus 41—A leading cause of diarrhea in children

et al. 2021

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Human adenovirus (HAdV) types F40 and F41 are a prominent cause of diarrhea and diarrhea-associated mortality in young children worldwide. These enteric HAdVs differ notably in tissue tropism and pathogenicity from respiratory and ocular adenoviruses, but the structural basis for this divergence has been unknown. Here, we present the first structure of an enteric HAdV—HAdV-F41—determined by cryo–electron microscopy to a resolution of 3.8 Å. The structure reveals extensive alterations to the virion exterior as compared to nonenteric HAdVs, including a unique arrangement of capsid protein IX. The structure also provides new insights into conserved aspects of HAdV architecture such as a proposed location of core protein V, which links the viral DNA to the capsid, and assembly-induced conformational changes in the penton base protein. Our findings provide the structural basis for adaptation of enteric HAdVs to a fundamentally different tissue tropism.

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Section: Introductionmentioning

confidence: 99%

The structure of enteric human adenovirus 41—A leading cause of diarrhea in children

et al. 2021

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“…To solve this limitation, vaccines can be developed from rare or low-prevalent human serotypes such as HAd2, HAd26, HAd35, HAd48, or HAd64 or from adenoviruses from non-human primates ( Bots and Hoeben, 2020 ; Garofalo et al, 2020 ). Nevertheless, in the context of replication-competent vaccines, employing the first strategy seems the safest option for vaccination, as non-human virus zoonoses could potentially arise from the use of adenoviruses from other animals ( Bots and Hoeben, 2020 ; Garofalo et al, 2020 ). Therefore, improving viruses such as HAd5 is a promising strategy in adenoviral-based vaccine development.…”

Section: Adenovirus-based Vaccinesmentioning

confidence: 99%

Codon Usage and Adenovirus Fitness: Implications for Vaccine Development

et al. 2021

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Vaccination is the most effective method to date to prevent viral diseases. It intends to mimic a naturally occurring infection while avoiding the disease, exposing our bodies to viral antigens to trigger an immune response that will protect us from future infections. Among different strategies for vaccine development, recombinant vaccines are one of the most efficient ones. Recombinant vaccines use safe viral vectors as vehicles and incorporate a transgenic antigen of the pathogen against which we intend to generate an immune response. These vaccines can be based on replication-deficient viruses or replication-competent viruses. While the most effective strategy involves replication-competent viruses, they must be attenuated to prevent any health hazard while guaranteeing a strong humoral and cellular immune response. Several attenuation strategies for adenoviral-based vaccine development have been contemplated over time. In this paper, we will review them and discuss novel approaches based on the principle that protein synthesis from individual genes can be modulated by codon usage bias manipulation. We will summarize vaccine approaches that consider recoding of viral proteins to produce adenoviral attenuation and recoding of the transgene antigens for both viral attenuation and efficient viral epitope expression.

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“…Adenoviral (Ad) vector vaccines also represent a promising modern vaccine platform, as a variety of Ad vector vaccines have reached human clinical trials for infectious disease and cancer [ 88 ]. Since first-generation Adenovirus platforms (Ad5) have the disadvantage of induction of adenovirus neutralizing antibodies, a second-generation adenovirus vaccine platform with four deletions enabling multiple homologous doses is being used to develop COVID-19 vaccine [ 89 , 90 ]. Specific targeting of an adenovirus to dendritic cells has been found to be very critical for the efficacy of the Ad vector-based vaccine [ 91 ].…”

Section: Covid-19 and Vaccine Developmentmentioning

confidence: 99%

Emerging Prevention and Treatment Strategies to Control COVID-19

et al. 2020

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has now become a serious global threat after inflicting more than 8 million infections and 425,000 deaths in less than 6 months. Currently, no definitive treatment or prevention therapy exists for COVID-19. The unprecedented rise of this pandemic has rapidly fueled research efforts to discover and develop new vaccines and treatment strategies against this novel coronavirus. While hundreds of vaccines/therapeutics are still in the preclinical or early stage of clinical development, a few of them have shown promising results in controlling the infection. Here, in this review, we discuss the promising vaccines and treatment options for COVID-19, their challenges, and potential alternative strategies.

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Prospects of Replication-Deficient Adenovirus Based Vaccine Development against SARS-CoV-2

Cited by 16 publications

References 66 publications

The structure of enteric human adenovirus 41—A leading cause of diarrhea in children

The structure of enteric human adenovirus 41—A leading cause of diarrhea in children

Codon Usage and Adenovirus Fitness: Implications for Vaccine Development

Emerging Prevention and Treatment Strategies to Control COVID-19

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