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<p>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. </p><p>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.</p><p>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.</p>
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