Protective Transfer: Maternal passive immunization with a rotavirus-neutralizing dimeric IgA protects against rotavirus disease in suckling neonates

Langel, Stephanie N.; Steppe, Justin; Chang, Jerry; Travieso, Tatianna; Webster, Helen; Otero, Claire E.; Williamson, Lauren E.; Crowe, James E.; Greenberg, Harry B.; Wu, Huali; Hornik, Christoph; Mansouri, Katayoun; Edward, Robert; Stalls, Victoria; Acharya, Priyamvada; Blasi, Maria Di; Permar, Sallie R.

doi:10.1101/2021.09.21.461116

Cited by 4 publications

(1 citation statement)

References 49 publications

(45 reference statements)

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“…Finally, chimeric viruses could be used to test new therapeutic strategies targeting the human outer capsid protein. This would be especially useful for testing monoclonal antibodies specific for human rotavirus strains [18,19].…”

Section: Discussionmentioning

confidence: 99%

Chimeric Viruses Enable Study of Antibody Responses to Human Rotaviruses in Mice

Woodyear,

Chandler,

Kawagishi

et al. 2024

Preprint

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The leading cause of gastroenteritis in children under the age of five is rotavirus infection, accounting for 37% of diarrhoeal deaths in infants and young children globally. Oral rotavirus vaccines have been widely incorporated into national immunisation programs, but whilst these vaccines have excellent efficacy in high-income countries, they protect less than 50% of vaccinated individuals in low- and middle-income countries. In order to facilitate the development of improved vaccine strategies, a greater understanding of the immune response to existing vaccines is urgently needed. However, the use of mouse models to study immune responses to human rotavirus strains is currently limited as rotaviruses are highly species-specific and replication of human rotaviruses is minimal in mice. To enable characterisation of immune responses to human rotavirus in mice, we have generated chimeric viruses that combat the issue of rotavirus host range restriction. Using reverse genetics, the rotavirus outer capsid proteins (VP4 and VP7) from either human or murine rotavirus strains were encoded in a murine rotavirus backbone. Neonatal mice were infected with chimeric viruses and monitored daily for development of diarrhoea. Stool samples were collected to quantify viral shedding, and antibody responses were comprehensively evaluated. We demonstrated that chimeric rotaviruses were able to efficiently replicate in mice. Moreover, the chimeric rotavirus containing human rotavirus outer capsid proteins elicited a robust antibody response to human rotavirus antigens, whilst the control chimeric murine rotavirus did not. This chimeric human rotavirus therefore provides a new strategy for studying human rotavirus-specific immunity, and could be used to investigate factors causing variability in rotavirus vaccine efficacy. This small animal platform therefore has the potential to test the efficacy of new vaccines and antibody-based therapeutics.

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Section: Discussionmentioning

confidence: 99%

Chimeric Viruses Enable Study of Antibody Responses to Human Rotaviruses in Mice

Woodyear,

Chandler,

Kawagishi

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

Correlates of immune protection against human rotaviruses: natural infection and vaccination

Latifi,

Kachooei,

Jalilvand

et al. 2024

Arch Virol

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Prenatal Immunization to Prevent Viral Disease Outcomes During Pregnancy and Early Life

Goswami¹,

Pavon²,

Miller³

et al. 2022

Front.Virol.

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Pregnancy significantly elevates the risk of developing severe viral diseases, which can have a detrimental effect on fetal development and increases maternal mortality. In addition, certain viruses can be transmitted vertically from mother to babies, either in utero, during delivery, or postnatally during breastfeeding, resulting in congenital or neonatal diseases and associated sequelae. While neonates are highly susceptible to viral infections and severe disease outcomes, due to the immaturity of their developing immune system, virus-specific maternal antibodies transferred either trans-placentally or via breast milk provide protection to infants against intestinal, respiratory, or systemic infections, during the first months of life. Thus, maternal prenatal immunization is important not only to protect pregnant women from viral diseases, but also to prevent infection and/or improve disease outcomes for the fetuses and neonates via passively transferred antibodies. In this review, we discuss the protective role of maternal antibodies against three categories of viruses: (i) viruses that cause severe maternal disease outcomes with mainly indirect consequences to the fetus (e.g. SARS-CoV-2, influenza, DENV, filovirus), (ii) those that are vertically transmitted from mother to their infants and cause congenital diseases (e.g. HIV, ZIKV and CMV), and (iii) those that cause elevated disease severity among neonates and infants postnatally (e.g. RSV, Rotavirus, Norovirus, HSV and HBV). Furthermore, we review relevant pre-clinical animal models that can be employed to develop novel immunization strategies against these viruses to enhance protection of pregnant women and their babies.

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Protective Transfer: Maternal passive immunization with a rotavirus-neutralizing dimeric IgA protects against rotavirus disease in suckling neonates

Cited by 4 publications

References 49 publications

Chimeric Viruses Enable Study of Antibody Responses to Human Rotaviruses in Mice

Chimeric Viruses Enable Study of Antibody Responses to Human Rotaviruses in Mice

Correlates of immune protection against human rotaviruses: natural infection and vaccination

Prenatal Immunization to Prevent Viral Disease Outcomes During Pregnancy and Early Life

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