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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 sub-lethal challenge of 10-week old A129 mice born to and/or nursed by DENV1-immune mothers.10-week old A129 mice from DD, DN, ND and NN groups were iv. infected with 106 PFU DENV2. (A) Survival rate and (B) clinical score of individual group (0: Healthy; 1: Ruffled fur; 2: Hunched back; 3: Diarrhoea; 4: Lethargic; 5: Moribund) (n = 6–10).
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pntd.0004805.g005: DENV2 sub-lethal challenge of 10-week old A129 mice born to and/or nursed by DENV1-immune mothers.10-week old A129 mice from DD, DN, ND and NN groups were iv. infected with 106 PFU DENV2. (A) Survival rate and (B) clinical score of individual group (0: Healthy; 1: Ruffled fur; 2: Hunched back; 3: Diarrhoea; 4: Lethargic; 5: Moribund) (n = 6–10).

Mentions: Based on the ELISA results, 10-week old DN mice had negligible levels of anti-DENV1 IgG whereas 10-week old ND mice still displayed significant levels of these antibodies (Fig 4A). To test whether such difference may translate into differential disease outcomes, 10-week old mice from the different groups were challenged with a sub-lethal dose of DENV2. Mice in ND and DD groups displayed disease enhancement with majority of the mice being moribund by day 4–5 post-infection (Fig 5A). In contrast, majority of the mice from DN group survived and displayed moderate clinical manifestations that were comparable to the NN control group (Fig 5B).


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 sub-lethal challenge of 10-week old A129 mice born to and/or nursed by DENV1-immune mothers.10-week old A129 mice from DD, DN, ND and NN groups were iv. infected with 106 PFU DENV2. (A) Survival rate and (B) clinical score of individual group (0: Healthy; 1: Ruffled fur; 2: Hunched back; 3: Diarrhoea; 4: Lethargic; 5: Moribund) (n = 6–10).
© Copyright Policy
Related In: Results  -  Collection

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

pntd.0004805.g005: DENV2 sub-lethal challenge of 10-week old A129 mice born to and/or nursed by DENV1-immune mothers.10-week old A129 mice from DD, DN, ND and NN groups were iv. infected with 106 PFU DENV2. (A) Survival rate and (B) clinical score of individual group (0: Healthy; 1: Ruffled fur; 2: Hunched back; 3: Diarrhoea; 4: Lethargic; 5: Moribund) (n = 6–10).
Mentions: Based on the ELISA results, 10-week old DN mice had negligible levels of anti-DENV1 IgG whereas 10-week old ND mice still displayed significant levels of these antibodies (Fig 4A). To test whether such difference may translate into differential disease outcomes, 10-week old mice from the different groups were challenged with a sub-lethal dose of DENV2. Mice in ND and DD groups displayed disease enhancement with majority of the mice being moribund by day 4–5 post-infection (Fig 5A). In contrast, majority of the mice from DN group survived and displayed moderate clinical manifestations that were comparable to the NN control group (Fig 5B).

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