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Relative Contribution of Dengue IgG Antibodies Acquired during Gestation or Breastfeeding in Mediating Dengue Disease Enhancement and Protection in Type I Interferon Receptor-Deficient Mice.

Lee PX, Ong LC, Libau EA, Alonso S - PLoS Negl Trop Dis (2016)

Bottom Line: On the other hand, in the context of homologous infection, breastfeeding conferred protection.Furthermore, measurement of dengue-specific antibody titres over time in mice born to dengue immune mothers revealed a biphasic pattern of antibody decay as reported in humans.Should such contribution be established in humans as well, it may have important implications for the development of guidelines to dengue-immune breastfeeding mothers.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

ABSTRACT
Dengue virus (DENV) causes a spectrum of diseases ranging from self-limiting dengue fever to severe conditions such as haemorrhagic fever and dengue shock syndrome. Antibody-dependent enhancement (ADE) is thought to explain the occurrence of severe dengue whereby pre-existing binding but non-neutralising antibodies enhance DENV infection. The ADE phenomenon is supported by epidemiological findings that infants that born to dengue immune mothers are at greater risk to develop severe dengue upon primary infection. The role of maternally acquired dengue-specific antibodies in disease enhancement was recently recapitulated in a mouse model where mice born to DENV1-immune mothers experienced enhanced disease severity upon DENV2 infection. Here, this study investigates the relative contribution of maternal dengue-specific antibodies acquired during gestation and breastfeeding in dengue disease. Using a surrogate breastfeeding mother experimental approach, we showed that majority of the maternal dengue-specific antibodies were acquired during breastfeeding and conferred an extended enhancement window. On the other hand, in the context of homologous infection, breastfeeding conferred protection. Furthermore, measurement of dengue-specific antibody titres over time in mice born to dengue immune mothers revealed a biphasic pattern of antibody decay as reported in humans. Our work provides evidence of the potential contribution of breast milk-acquired dengue-specific IgG antibodies in enhancement and protection against dengue. Should such contribution be established in humans as well, it may have important implications for the development of guidelines to dengue-immune breastfeeding mothers.

No MeSH data available.


Related in: MedlinePlus

DENV2-specific IgG titres in mice born to and/or nursed by DENV2-immune mothers.DENV2-specific IgG levels were measured by ELISA in sera from 5-week old mice born to and nursed by DENV2-immune or naïve mothers (n = 4–5). Dotted line denotes the limit of detection of the assay. *p<0.05 based on Mann-Whitney test comparing DN and ND against DD control.
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pntd.0004805.g006: DENV2-specific IgG titres in mice born to and/or nursed by DENV2-immune mothers.DENV2-specific IgG levels were measured by ELISA in sera from 5-week old mice born to and nursed by DENV2-immune or naïve mothers (n = 4–5). Dotted line denotes the limit of detection of the assay. *p<0.05 based on Mann-Whitney test comparing DN and ND against DD control.

Mentions: Besides being implicated in ADE, DENV-specific antibodies may also be involved in protection against infection. The protective role of dengue antibodies acquired from breast milk was thus examined. For this, a dengue homotypic model was set up where mice born to and nursed by DENV2-immune mothers were subsequently challenged with a lethal dose of the same DENV2 strain. The relative amounts of maternal DENV2 IgG acquired during gestation or from breastfeeding were again determined by switching pups at birth and measuring their systemic levels of DENV2 IgG at 5 weeks of age. Similar to the heterotypic ADE model, mice nursed by DENV2-immune mothers regardless of the immune status of their birth mothers (DD and ND) had comparable systemic levels of DENV2-IgG antibodies that were significantly higher than those measured in DN mice (born to DENV2-immune mothers but nursed by naïve mothers) (Fig 6). The neutralising activity (PRNT50) of sera against DENV2 displayed similar trends (Table 3). The comparable levels of DENV2-IgG antibodies in DD and ND groups again indicated that the main route of maternal dengue-IgG transfer is during breastfeeding.


Relative Contribution of Dengue IgG Antibodies Acquired during Gestation or Breastfeeding in Mediating Dengue Disease Enhancement and Protection in Type I Interferon Receptor-Deficient Mice.

Lee PX, Ong LC, Libau EA, Alonso S - PLoS Negl Trop Dis (2016)

DENV2-specific IgG titres in mice born to and/or nursed by DENV2-immune mothers.DENV2-specific IgG levels were measured by ELISA in sera from 5-week old mice born to and nursed by DENV2-immune or naïve mothers (n = 4–5). Dotted line denotes the limit of detection of the assay. *p<0.05 based on Mann-Whitney test comparing DN and ND against DD control.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4920417&req=5

pntd.0004805.g006: DENV2-specific IgG titres in mice born to and/or nursed by DENV2-immune mothers.DENV2-specific IgG levels were measured by ELISA in sera from 5-week old mice born to and nursed by DENV2-immune or naïve mothers (n = 4–5). Dotted line denotes the limit of detection of the assay. *p<0.05 based on Mann-Whitney test comparing DN and ND against DD control.
Mentions: Besides being implicated in ADE, DENV-specific antibodies may also be involved in protection against infection. The protective role of dengue antibodies acquired from breast milk was thus examined. For this, a dengue homotypic model was set up where mice born to and nursed by DENV2-immune mothers were subsequently challenged with a lethal dose of the same DENV2 strain. The relative amounts of maternal DENV2 IgG acquired during gestation or from breastfeeding were again determined by switching pups at birth and measuring their systemic levels of DENV2 IgG at 5 weeks of age. Similar to the heterotypic ADE model, mice nursed by DENV2-immune mothers regardless of the immune status of their birth mothers (DD and ND) had comparable systemic levels of DENV2-IgG antibodies that were significantly higher than those measured in DN mice (born to DENV2-immune mothers but nursed by naïve mothers) (Fig 6). The neutralising activity (PRNT50) of sera against DENV2 displayed similar trends (Table 3). The comparable levels of DENV2-IgG antibodies in DD and ND groups again indicated that the main route of maternal dengue-IgG transfer is during breastfeeding.

Bottom Line: On the other hand, in the context of homologous infection, breastfeeding conferred protection.Furthermore, measurement of dengue-specific antibody titres over time in mice born to dengue immune mothers revealed a biphasic pattern of antibody decay as reported in humans.Should such contribution be established in humans as well, it may have important implications for the development of guidelines to dengue-immune breastfeeding mothers.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

ABSTRACT
Dengue virus (DENV) causes a spectrum of diseases ranging from self-limiting dengue fever to severe conditions such as haemorrhagic fever and dengue shock syndrome. Antibody-dependent enhancement (ADE) is thought to explain the occurrence of severe dengue whereby pre-existing binding but non-neutralising antibodies enhance DENV infection. The ADE phenomenon is supported by epidemiological findings that infants that born to dengue immune mothers are at greater risk to develop severe dengue upon primary infection. The role of maternally acquired dengue-specific antibodies in disease enhancement was recently recapitulated in a mouse model where mice born to DENV1-immune mothers experienced enhanced disease severity upon DENV2 infection. Here, this study investigates the relative contribution of maternal dengue-specific antibodies acquired during gestation and breastfeeding in dengue disease. Using a surrogate breastfeeding mother experimental approach, we showed that majority of the maternal dengue-specific antibodies were acquired during breastfeeding and conferred an extended enhancement window. On the other hand, in the context of homologous infection, breastfeeding conferred protection. Furthermore, measurement of dengue-specific antibody titres over time in mice born to dengue immune mothers revealed a biphasic pattern of antibody decay as reported in humans. Our work provides evidence of the potential contribution of breast milk-acquired dengue-specific IgG antibodies in enhancement and protection against dengue. Should such contribution be established in humans as well, it may have important implications for the development of guidelines to dengue-immune breastfeeding mothers.

No MeSH data available.


Related in: MedlinePlus