Comparison of replicating and nonreplicating vaccines against SARS-CoV-2

Mudrick, Haley; Massey, Shane; McGlinch, Erin; Parrett, Brian J.; Hemsath, Jack R.; Barry, Michael Kevin; Rubin, Jeffrey D.; Uzendu, Chisom; Hansen, Michael J.; Erskine, Courtney L.; Keulen, Virginia P. Van; Drelich, Aleksandra; Panos, Joseph A.; Fida, Madiha; Suh, Gina A.; Peikert, Tobias; Block, Matthew S.; Tseng, Chien-Te; Olivier, Gloria; Barry, Michael A.

doi:10.1126/sciadv.abm8563

Cited by 7 publications

(3 citation statements)

References 37 publications

(62 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This phenomenon is similar to previous findings suggesting that replication-competent recombinant adenoviruses (RCA) do not replicate efficiently in ICR mice [ 50 ]. However, it has been reported that wild-type human adenoviruses can replicate efficiently in Syrian hamsters and non-human primates [ 51 ], suggesting that RCA may pose potential safety risk. Meanwhile, no body weight changes and clinical symptom were observed in mice immunized with Adv-RVDG.…”

Section: Discussionmentioning

confidence: 99%

A modified recombinant adenovirus vector containing dual rabies virus G expression cassettes confers robust and long-lasting humoral immunity in mice, cats, and dogs

Zhang,

Fang,

Wang

et al. 2024

Emerging Microbes & Infections

View full text Add to dashboard Cite

During the COVID-19 epidemic, the incidence of rabies has increased in several countries, especially in remote and disadvantaged areas, due to inadequate surveillance and declining immunization coverage. Multiple vaccinations with inactivated rabies virus vaccines for pre- or post-exposure prophylaxis are considered inefficient, expensive and impractical in developing countries. Herein, three modified human recombinant adenoviruses type 5 designated Adv-RVG, Adv-E1-RVG, and Adv-RVDG, carrying rabies virus G (RVG) expression cassettes in various combinations within E1 or E3 genomic regions, were constructed to serve as rabies vaccine candidates. Adv-RVDG mediated greater RVG expression both in vitro and in vivo and induced a more robust and durable humoral immune response than the rabies vaccine strain SAD-L16, Adv-RVG, and Adv-E1-RVG by more effectively activating the dendritic cells (DCs) – follicular helper T (Tfh) cells – germinal centre (GC) / memory B cells (MBCs) – long-lived plasma cells (LLPCs) axis with 100% survival after a lethal RABV challenge in mice during the 24-week study period. Similarly, dogs and cats immunized with Adv-RVDG showed stronger and longer-lasting antibody responses than those vaccinated with a commercial inactivated rabies vaccine and showed good tolerance to Adv-RVDG. In conclusion, our study demonstrated that simultaneous insertion of protective antigens into the E1 and E3 genomic regions of adenovirus vector can significantly enhance the immunogenicity of adenoviral-vectored vaccines, providing a theoretical and practical basis for the subsequent development of multivalent and multi-conjugated vaccines using recombinant adenovirus platform. Meanwhile, our data suggest Adv-RVDG is a safe, efficient, and economical vaccine for mass-coverage immunization.

show abstract

Section: Discussionmentioning

confidence: 99%

A modified recombinant adenovirus vector containing dual rabies virus G expression cassettes confers robust and long-lasting humoral immunity in mice, cats, and dogs

Zhang,

Fang,

Wang

et al. 2024

Emerging Microbes & Infections

View full text Add to dashboard Cite

show abstract

“…The American pharmaceutical company Tetherex and the Mayo Clinic developed a replicating adenoviral vector ( SC-Ad6-1 ) that encodes a full-length spike; this vaccine is administered intranasally, and it aims to induce mucosal immunity [ 173 ] (Table 3 ). The single-cycle adenovirus replicates its genome (including the encoded spike transgene) 10,000 times but does not produce infectious virions.…”

Section: Pan-coronavirus Vaccine Approachesmentioning

confidence: 99%

“…The single-cycle adenovirus replicates its genome (including the encoded spike transgene) 10,000 times but does not produce infectious virions. SC-Ad6-1 was shown to produce 100-fold more spike protein and provided better protection in hamsters than a replication-defective Ad [ 173 ]. SC-Ad6-1 has entered Phase-I testing in Australia.…”

Section: Pan-coronavirus Vaccine Approachesmentioning

confidence: 99%

In search of a pan-coronavirus vaccine: next-generation vaccine design and immune mechanisms

Cankat,

Demael,

Swadling

2023

Cell Mol Immunol

View full text Add to dashboard Cite

Members of the coronaviridae family are endemic to human populations and have caused several epidemics and pandemics in recent history. In this review, we will discuss the feasibility of and progress toward the ultimate goal of creating a pan-coronavirus vaccine that can protect against infection and disease by all members of the coronavirus family. We will detail the unmet clinical need associated with the continued transmission of SARS-CoV-2, MERS-CoV and the four seasonal coronaviruses (HCoV-OC43, NL63, HKU1 and 229E) in humans and the potential for future zoonotic coronaviruses. We will highlight how first-generation SARS-CoV-2 vaccines and natural history studies have greatly increased our understanding of effective antiviral immunity to coronaviruses and have informed next-generation vaccine design. We will then consider the ideal properties of a pan-coronavirus vaccine and propose a blueprint for the type of immunity that may offer cross-protection. Finally, we will describe a subset of the diverse technologies and novel approaches being pursued with the goal of developing broadly or universally protective vaccines for coronaviruses.

show abstract