Evaluation of Vaccine‐induced Maternal Antibody Transfer and Impact on Infant Immune Responses in the Rabbit Model

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Staats, Herman F.

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Jones, Dorothy I

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2019-06-07T19:49:16Z

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2020-05-21T08:17:13Z

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2019

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Pathology

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Maternal vaccination protects infants through transplacental transfer of vaccine-specific maternal IgG and milk transfer of IgG and IgA antibodies from mother to child. I performed experiments in the rabbit model, which models human maternal antibody transfer, to determine how maternal HIV vaccine formulations impact the passive transfer of maternal gp120-specific antibodies and to investigate potential side effects of vaccine-elicited maternal antibodies. Since the mammary gland is part of the mucosal immune system, mucosal administration of maternal vaccines may enhance milk transfer of maternal antibodies; however, the tendency of mucosal vaccines to induce lower serum IgG responses than injected vaccines could decrease transplacental transfer. Optimized intranasal boosting during pregnancy resulted in similar concentrations of gp120-specific IgG in infant serum, however milk gp120-specific IgA concentrations were not enhanced. Furthermore, intranasal boosting with chitosan-adjuvanted vaccines resulted in significantly higher transplacental transfer of maternal antibody than MPL-adjuvanted vaccines even though both formulations induced similar levels of gp120-specific IgG in maternal serum, indicating that maternal vaccine adjuvants may alter transplacental transfer of maternal antibodies.

Infant rabbits born to mothers that received the IM and IN maternal vaccine regimens were vaccinated with gp120 with or without adjuvant to investigate maternal antibodies interference with infant antibody responses to vaccination. Maternal gp120-specific IgG inhibited infant vaccination with unadjuvanted gp120, however inclusion of either alum or GLA-SE, a TLR4 agonist in an oil-in-water emulsion, was able to induce active antibody responses in infants. Furthermore, infant rabbits that received an alum-adjuvanted vaccine in the presence of maternal antibodies had enhanced serum gp120-specific and V1V2-specific IgG that infants vaccinated without maternal gp120-specific IgG present. GLA-SE did not enhance infant antibody responses to vaccination. Thus, maternal anti-gp120 IgG can enhance or inhibit infant antigen-specific responses to vaccination depending on the infant vaccine adjuvant.

While maternal antibodies protect the infant, there is evidence that some viruses, including HIV and Zika, use maternal antibodies to be transferred across the placenta, facilitating mother-to-child-transmission. As HIV infects and replicates poorly in rabbits, a rabbit model of Zika virus challenge was established and the impact of maternal vaccination or anti-flavivirus monoclonal antibody on pathogenesis was investigated. While Zika virus-specific antibodies altered maternal cytokine response to challenge, and there was an increased risk for fetal resorption in vaccinated rabbits compared to naïve rabbits, there was no significant impact on placental Zika virus RNA concentration. While further refinement is needed, Zika virus challenge of rabbits is a promising in vivo model for investigating the transplacental transfer of maternal antibody-pathogen complexes.

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https://hdl.handle.net/10161/18785

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Pathology

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Immunology

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Medicine

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HIV

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Maternal Antibodies

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Pregnancy

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Rabbit

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Vaccine

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Zika

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Evaluation of Vaccine‐induced Maternal Antibody Transfer and Impact on Infant Immune Responses in the Rabbit Model

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Dissertation

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11

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