Development of an anti-guinea pig CD4 monoclonal antibody for depletion of CD4+ T cells in vivo

Banasik, Brianne N.; Perry, Clarice L.; Keith, Celeste A.; Bourne, Nigel; Schäfer, Hubert; Milligan, Gregg N.

doi:10.1016/j.jim.2019.112654

Cited by 3 publications

(1 citation statement)

References 41 publications

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“…We specifically plan to assess the efficacy of the passive transfer of vaccinated immune serum against lethal challenges and assess the contribution of the cell-mediated immune response via depletion of CD4+ T cells, CD8+ T cells, or both. These studies will be possible as guinea pig-specific reagents for the depletion of T cells have recently been developed 53 . We also plan to assess the durability of the immune response and the protective efficacy of a single-dose regimen, as well as protection against heterologous LASV clades.…”

Section: Discussionmentioning

confidence: 99%

A Lassa virus mRNA vaccine confers protection but does not require neutralizing antibody in a guinea pig model of infection

Ronk,

Lloyd,

Zhang

et al. 2023

Nat Commun

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Lassa virus is a member of the Arenaviridae family, which causes human infections ranging from asymptomatic to severe hemorrhagic disease with a high case fatality rate. We have designed and generated lipid nanoparticle encapsulated, modified mRNA vaccines that encode for the wild-type Lassa virus strain Josiah glycoprotein complex or the prefusion stabilized conformation of the Lassa virus glycoprotein complex. Hartley guinea pigs were vaccinated with two 10 µg doses, 28 days apart, of either construct. Vaccination induced strong binding antibody responses, specific to the prefusion conformation of glycoprotein complex, which were significantly higher in the prefusion stabilized glycoprotein complex construct group and displayed strong Fc-mediated effects. However, Lassa virus-neutralizing antibody activity was detected in some but not all animals. Following the challenge with a lethal dose of the Lassa virus, all vaccinated animals were protected from death and severe disease. Although the definitive mechanism of protection is still unknown, and assessment of the cell-mediated immune response was not investigated in this study, these data demonstrate the promise of mRNA as a vaccine platform against the Lassa virus and that protection against Lassa virus can be achieved in the absence of virus-neutralizing antibodies.

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Section: Discussionmentioning

confidence: 99%

A Lassa virus mRNA vaccine confers protection but does not require neutralizing antibody in a guinea pig model of infection

Ronk,

Lloyd,

Zhang

et al. 2023

Nat Commun

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Impact of CD4+ T lymphocytes on the cellular and molecular milieu of the vaginal mucosa following HSV-2 challenge of immune guinea pigs

Bourne,

Keith,

Miller

et al. 2023

Virology

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CD4⁺but not CD8⁺T cells are required for protection against severe guinea pig cytomegalovirus infections

Rollman,

Berkebile,

Hicks

et al. 2024

Preprint

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Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus and the leading cause of infectious disease related birth defects worldwide. How the immune response modulates the risk of intrauterine transmission of HCMV after maternal infection remains poorly understood. Maternal T cells likely play a critical role in preventing infection at the maternal-fetal interface and limiting spread across the placenta, but concerns exist that immune responses to infection may also cause placental dysfunction and adverse pregnancy outcomes. This study investigated the role of CD4+and CD8+T cells in a guinea pig model of primary cytomegalovirus infection. Monoclonal antibodies specific to guinea pig CD4 and CD8 were used to deplete T cells in non- pregnant and in pregnant guinea pigs after mid-gestation. CD4+T cell depletion increased the severity of illness, caused significantly elevated viral loads, and increased the rate of congenital guinea pig cytomegalovirus (GPCMV) infection relative to animals treated with control antibody. CD8+T cell depletion was comparably well tolerated and did not significantly affect the weight of infected guinea pigs or viral loads in their blood or tissue. However, significantly more viral genomes and transcripts were detected in the placenta and decidua of CD8+T cell depleted dams post-infection. This study corroborates earlier findings made in nonhuman primates that maternal CD4+T cells play a critical role in limiting the severity of primary CMV infection during pregnancy while also revealing that other innate and adaptive immune responses can compensate for an absent CD8+T cell response in α-CD8-treated guinea pigs.Author SummaryCongenital cytomegalovirus infection is a leading cause of adverse pregnancy outcomes and preventable disability in children. Using guinea pigs, a well-established small animal model of congenital infection and intrauterine development, this study tested how depleting T cells affects the course of primary cytomegalovirus infections. Severe illness and high rates of congenital infection were observed when helper CD4+T cells were depleted. The depletion of killer CD8+T cells did not affect the severity of disease or the rate of congenital infection but did increase the amount of virus that was detected in the placenta. A greater understanding how an immune response can prevent the infection of the placenta and developing offspring is needed to inform vaccine and therapeutic development. This study not only describes a new reagent that can be used to study the guinea pig immune system but also sheds new light in how adaptive immunity regulates congenital viral infection.

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Development of an anti-guinea pig CD4 monoclonal antibody for depletion of CD4+ T cells in vivo

Cited by 3 publications

References 41 publications

A Lassa virus mRNA vaccine confers protection but does not require neutralizing antibody in a guinea pig model of infection

A Lassa virus mRNA vaccine confers protection but does not require neutralizing antibody in a guinea pig model of infection

Impact of CD4+ T lymphocytes on the cellular and molecular milieu of the vaginal mucosa following HSV-2 challenge of immune guinea pigs

CD4⁺but not CD8⁺T cells are required for protection against severe guinea pig cytomegalovirus infections

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Development of an anti-guinea pig CD4 monoclonal antibody for depletion of CD4+ T cells in vivo

Cited by 3 publications

References 41 publications

A Lassa virus mRNA vaccine confers protection but does not require neutralizing antibody in a guinea pig model of infection

A Lassa virus mRNA vaccine confers protection but does not require neutralizing antibody in a guinea pig model of infection

Impact of CD4+ T lymphocytes on the cellular and molecular milieu of the vaginal mucosa following HSV-2 challenge of immune guinea pigs

CD4+but not CD8+T cells are required for protection against severe guinea pig cytomegalovirus infections

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CD4⁺but not CD8⁺T cells are required for protection against severe guinea pig cytomegalovirus infections