Leveraging Beneficial Off-Target Effects of Live-Attenuated Rotavirus Vaccines

Benedicto-Matambo, Prisca; Bines, Julie E; Malamba-Banda, Chikondi; Shawa, Isaac Thom; Barnes, Kayla G.; Kamng’ona, Arox W; Hungerford, Daniel; Jambo, Kondwani; Iturriza‐Gómara, Miren; Cunliffe, Nigel A.; Flanagan, Katie L.; Jere, Khuzwayo C.

doi:10.3390/vaccines10030418

Cited by 6 publications

(3 citation statements)

References 106 publications

(168 reference statements)

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“…Rotavirus A (RVA) is the leading cause associated with viral acute gastroenteritis in children worldwide, accounting for nearly 128,500 under-five deaths annually, even with the increasing implementation of universal RVA vaccination [ 1 ]. To date, over 100 countries have incorporated RVA vaccines into their national immunization programs (NPIs) [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Genomic Constellation of Human Rotavirus G8 Strains in Brazil over a 13-Year Period: Detection of the Novel Bovine-like G8P[8] Strains with the DS-1-like Backbone

Medeiros

França

Viana

et al. 2023

Viruses

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Rotavirus (RVA) G8 is frequently detected in animals, but only occasionally in humans. G8 strains, however, are frequently documented in nations in Africa. Recently, an increase in G8 detection was observed outside Africa. The aims of the study were to monitor G8 infections in the Brazilian human population between 2007 and 2020, undertake the full-genotype characterization of the four G8P[4], six G8P[6] and two G8P[8] RVA strains and conduct phylogenetic analysis in order to understand their genetic diversity and evolution. A total of 12,978 specimens were screened for RVA using ELISA, PAGE, RT-PCR and Sanger sequencing. G8 genotype represented 0.6% (15/2434) of the entirely RVA-positive samples. G8P[4] comprised 33.3% (5/15), G8P[6] 46.7% (7/15) and G8P[8] 20% (3/15). All G8 strains showed a short RNA pattern. All twelve selected G8 strains displayed a DS-1-like genetic backbone. The whole-genotype analysis on a DS-1-like backbone identified four different genotype-linage constellations. According to VP7 analysis, the Brazilian G8P[8] strains with the DS-1-like backbone strains were derived from cattle and clustered with newly DS-1-like G1/G3/G9/G8P[8] strains and G2P[4] strains. Brazilian IAL-R193/2017/G8P[8] belonged to a VP1/R2.XI lineage and were grouped with bovine-like G8P[8] strains with the DS-1-like backbone strains detected in Asia. Otherwise, the Brazilian IAL-R558/2017/G8P[8] possess a “Distinct” VP1/R2 lineage never previously described and grouped apart from any of the DS-1-like reference strains. Collectively, our findings suggest that the Brazilian bovine-like G8P[8] strains with the DS-1-like backbone strains are continuously evolving and likely reassorting with local RVA strains rather than directly relating to imports from Asia. The Brazilian G8P[6]-DS-1-like strains have been reassorted with nearby co-circulating American strains of the same DS-1 genotype constellation. However, phylogenetic analyses revealed that these strains have some genetic origin from Africa. Finally, rather than being African-born, Brazilian G8P[4]-DS-1-like strains were likely imported from Europe. None of the Brazilian G8 strains examined here exhibited signs of recent zoonotic reassortment. G8 strains continued to be found in Brazil according to their intermittent and localized pattern, thus, does not suggest that a potential emergence is taking place in the country. Our research demonstrates the diversity of G8 RVA strains in Brazil and adds to the understanding of G8P[4]/P[6]/P[8] RVA genetic diversity and evolution on a global scale.

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Section: Introductionmentioning

confidence: 99%

Genomic Constellation of Human Rotavirus G8 Strains in Brazil over a 13-Year Period: Detection of the Novel Bovine-like G8P[8] Strains with the DS-1-like Backbone

Medeiros

França

Viana

et al. 2023

Viruses

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“…Finally, despite its favorable qualities, mRNA remains a vehicle, and we cannot expect a single tool to solve the problems of all antimicrobial vaccines [ 126 ]. Think about the extraordinary success of pneumococcal vaccines based on polysaccharides [ 127 ] and the beneficial off-target effects of live rotavirus vaccines [ 128 ].…”

Section: Future Directionsmentioning

confidence: 99%

mRNA Technology and Mucosal Immunization

Toniolo,

Maccari,

Camussi

2024

Vaccines

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Current mRNA vaccines are mainly administered via intramuscular injection, which induces good systemic immunity but limited mucosal immunity. Achieving mucosal immunity through mRNA vaccination could diminish pathogen replication at the entry site and reduce interhuman transmission. However, delivering mRNA vaccines to mucosae faces challenges like mRNA degradation, poor entry into cells, and reactogenicity. Encapsulating mRNA in extracellular vesicles may protect the mRNA and reduce reactogenicity, making mucosal mRNA vaccines possible. Plant-derived extracellular vesicles from edible fruits have been investigated as mRNA carriers. Studies in animals show that mRNA vehiculated in orange-derived extracellular vesicles can elicit both systemic and mucosal immune responses when administered by the oral, nasal, or intramuscular routes. Once lyophilized, these products show remarkable stability. The optimization of mRNA to improve translation efficiency, immunogenicity, reactogenicity, and stability can be obtained through adjustments of the 5′cap region, poly-A tail, codons selection, and the use of nucleoside analogues. Recent studies have also proposed self-amplifying RNA vaccines containing an RNA polymerase as well as circular mRNA constructs. Data from parenterally primed animals demonstrate the efficacy of nasal immunization with non-adjuvanted protein, and studies in humans indicate that the combination of a parenteral vaccine with the natural exposure of mucosae to the same antigen provides protection and reduces transmission. Hence, mucosal mRNA vaccination would be beneficial at least in organisms pre-treated with parenteral vaccines. This practice could have wide applications for the treatment of infectious diseases.

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“…Live attenuated rotavirus vaccine has been proposed as a mechanism to protect against non-rotavirus gastroenteritis ( 78 ). However, this concept needs further evaluation because of a conflicting report ( 79 ).…”

Section: Lav-induced Nsementioning

confidence: 99%

Prospects on Repurposing a Live Attenuated Vaccine for the Control of Unrelated Infections

Seo

Seong

2022

Front. Immunol.

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Live vaccines use attenuated microbes to acquire immunity against pathogens in a safe way. As live attenuated vaccines (LAVs) still maintain infectivity, the vaccination stimulates diverse immune responses by mimicking natural infection. Induction of pathogen-specific antibodies or cell-mediated cytotoxicity provides means of specific protection, but LAV can also elicit unintended off-target effects, termed non-specific effects. Such mechanisms as short-lived genetic interference and non-specific innate immune response or long-lasting trained immunity and heterologous immunity allow LAVs to develop resistance to subsequent microbial infections. Based on their safety and potential for interference, LAVs may be considered as an alternative for immediate mitigation and control of unexpected pandemic outbreaks before pathogen-specific therapeutic and prophylactic measures are deployed.

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Leveraging Beneficial Off-Target Effects of Live-Attenuated Rotavirus Vaccines

Cited by 6 publications

References 106 publications

Genomic Constellation of Human Rotavirus G8 Strains in Brazil over a 13-Year Period: Detection of the Novel Bovine-like G8P[8] Strains with the DS-1-like Backbone

Genomic Constellation of Human Rotavirus G8 Strains in Brazil over a 13-Year Period: Detection of the Novel Bovine-like G8P[8] Strains with the DS-1-like Backbone

mRNA Technology and Mucosal Immunization

Prospects on Repurposing a Live Attenuated Vaccine for the Control of Unrelated Infections

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