Human Acquired Immunity to Rotavirus Disease and Correlates of Protection

Herrera, Daniel; Parra, Miguel Ramos; Franco, Manuel; Ángel, Juana

doi:10.1016/b978-0-12-802241-2.00013-4

Viral Gastroenteritis 2016

DOI: 10.1016/b978-0-12-802241-2.00013-4

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Human Acquired Immunity to Rotavirus Disease and Correlates of Protection

Daniel Herrera

Miguel Ramos Parra

Manuel Franco

et al.

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2019

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“…Despite the introduction of several live attenuated animal and human rotaviruses (RVs) as efficient oral vaccines, RVs continue to be the leading etiological agent for diarrhea mortality among children under 5 years of age worldwide (16). Improvement of these vaccines has been partially delayed because immunity to RV is incompletely understood (17,18). Our studies in children and adults infected with RV showed that RV-specific T cells (RV-T cells) circulate at frequencies below detection levels or at low frequencies (19) and have a poor functional profile (20), suggesting that RV has developed mechanisms to evade the immune response.…”

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confidence: 99%

LAP ⁺ Cells Modulate Protection Induced by Oral Vaccination with Rhesus Rotavirus in a Neonatal Mouse Model

Rey

Gil

Mateus

et al. 2019

J Virol

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Transforming growth factor β (TGF-β) has been shown to play a role in immunity against different pathogens in vitro and against parasites in vivo. However, its role in viral infections in vivo is incompletely understood. Using a neonatal mouse model of heterologous rhesus rotavirus (RV) vaccination, we show that the vaccine induced rotavirus-specific CD4 T cells, the majority of which lacked expression of KLRG1 or CD127, and a few regulatory rotavirus-specific CD4 T cells that expressed surface latency-associated peptide (LAP)–TGF-β. In these mice, inhibiting TGF-β, with both a neutralizing antibody and an inhibitor of TGF-β receptor signaling (activin receptor-like kinase 5 inhibitor [ALK5i]), did not change the development or intensity of the mild diarrhea induced by the vaccine, the rotavirus-specific T cell response, or protection against a subsequent challenge with a murine EC-rotavirus. However, mice treated with anti-LAP antibodies had improved protection after a homologous EC-rotavirus challenge, compared with control rhesus rotavirus-immunized mice. Thus, oral vaccination with a heterologous rotavirus stimulates regulatory RV-specific CD4 LAP-positive (LAP+) T cells, and depletion of LAP+ cells increases vaccine-induced protection. IMPORTANCE Despite the introduction of several live attenuated animal and human rotaviruses as efficient oral vaccines, rotaviruses continue to be the leading etiological agent for diarrhea mortality among children under 5 years of age worldwide. Improvement of these vaccines has been partially delayed because immunity to rotaviruses is incompletely understood. In the intestine (where rotavirus replicates), regulatory T cells that express latency-associated peptide (LAP) play a prominent role, which has been explored for many diseases but not specifically for infectious agents. In this paper, we show that neonatal mice given a live oral rotavirus vaccine develop rotavirus-specific LAP+ T cells and that depletion of these cells improves the efficiency of the vaccine. These findings may prove useful for the design of strategies to improve rotavirus vaccines.

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confidence: 99%

LAP ⁺ Cells Modulate Protection Induced by Oral Vaccination with Rhesus Rotavirus in a Neonatal Mouse Model

Rey

Gil

Mateus

et al. 2019

J Virol

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Human Acquired Immunity to Rotavirus Disease and Correlates of Protection

Cited by 1 publication

References 52 publications

LAP ⁺ Cells Modulate Protection Induced by Oral Vaccination with Rhesus Rotavirus in a Neonatal Mouse Model

LAP ⁺ Cells Modulate Protection Induced by Oral Vaccination with Rhesus Rotavirus in a Neonatal Mouse Model

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Human Acquired Immunity to Rotavirus Disease and Correlates of Protection

Cited by 1 publication

References 52 publications

LAP + Cells Modulate Protection Induced by Oral Vaccination with Rhesus Rotavirus in a Neonatal Mouse Model

LAP + Cells Modulate Protection Induced by Oral Vaccination with Rhesus Rotavirus in a Neonatal Mouse Model

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LAP ⁺ Cells Modulate Protection Induced by Oral Vaccination with Rhesus Rotavirus in a Neonatal Mouse Model

LAP ⁺ Cells Modulate Protection Induced by Oral Vaccination with Rhesus Rotavirus in a Neonatal Mouse Model