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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

The breastfeeding surrogate mother experiment.Adult female A129 mice were iv. infected with 106 PFU per mouse of DENV1. One week post-infection after virus clearance, the females were mated with naïve adult males. Age-matched naïve females were also mated concurrently. At birth, pups born to either DENV1-immune or naïve mothers were switched and nursed by naïve or dengue-immune mothers respectively. Control groups comprised of mice nursed by birth mothers were also included. DD: Born to and nursed by dengue-immune mother; DN: Born to dengue-immune mother, but nursed by naïve mother; ND: Born to naïve mother, but nursed by dengue-immune mother; NN: Born to and nursed by naïve mother.
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pntd.0004805.g001: The breastfeeding surrogate mother experiment.Adult female A129 mice were iv. infected with 106 PFU per mouse of DENV1. One week post-infection after virus clearance, the females were mated with naïve adult males. Age-matched naïve females were also mated concurrently. At birth, pups born to either DENV1-immune or naïve mothers were switched and nursed by naïve or dengue-immune mothers respectively. Control groups comprised of mice nursed by birth mothers were also included. DD: Born to and nursed by dengue-immune mother; DN: Born to dengue-immune mother, but nursed by naïve mother; ND: Born to naïve mother, but nursed by dengue-immune mother; NN: Born to and nursed by naïve mother.

Mentions: Adult A129 females were infected with 106 PFU per mouse of DENV1 or DENV2 via intravenous (iv) route. One week post-infection after virus clearance, the females were mated with naïve adult males. Age-matched naïve females were also mated concurrently. At birth, pups born to either dengue-immune or naïve mothers were switched and nursed by naïve or dengue-immune mothers respectively (Fig 1). Control groups comprised of mice nursed by birth mothers were also included. All pups were breastfed by the respective mothers and were weaned out 21 days later. At 5 and 10 weeks of age, these mice were challenged with either 106 PFU (sub-lethal dose) or 107 PFU (lethal dose) of DENV2 via iv route and monitored for survival and bled at specific time point for viremia determination. The infected animals were monitored daily for clinical manifestations. The scoring system used was: 0: Healthy; 1: Ruffled fur; 2: Hunched back; 3: Diarrhoea; 4: Lethargic; 5: Moribund. Survival rate was derived from the number of mice that were euthanized at moribund stage as evidenced by severe diarrhoea and extreme lethargy as described previously [11]. Serum collection was performed at various time points after birth for antibody measurement, or at day 4 post-infection to measure virus titres by plaque assay.


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)

The breastfeeding surrogate mother experiment.Adult female A129 mice were iv. infected with 106 PFU per mouse of DENV1. One week post-infection after virus clearance, the females were mated with naïve adult males. Age-matched naïve females were also mated concurrently. At birth, pups born to either DENV1-immune or naïve mothers were switched and nursed by naïve or dengue-immune mothers respectively. Control groups comprised of mice nursed by birth mothers were also included. DD: Born to and nursed by dengue-immune mother; DN: Born to dengue-immune mother, but nursed by naïve mother; ND: Born to naïve mother, but nursed by dengue-immune mother; NN: Born to and nursed by naïve mother.
© Copyright Policy
Related In: Results  -  Collection

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

pntd.0004805.g001: The breastfeeding surrogate mother experiment.Adult female A129 mice were iv. infected with 106 PFU per mouse of DENV1. One week post-infection after virus clearance, the females were mated with naïve adult males. Age-matched naïve females were also mated concurrently. At birth, pups born to either DENV1-immune or naïve mothers were switched and nursed by naïve or dengue-immune mothers respectively. Control groups comprised of mice nursed by birth mothers were also included. DD: Born to and nursed by dengue-immune mother; DN: Born to dengue-immune mother, but nursed by naïve mother; ND: Born to naïve mother, but nursed by dengue-immune mother; NN: Born to and nursed by naïve mother.
Mentions: Adult A129 females were infected with 106 PFU per mouse of DENV1 or DENV2 via intravenous (iv) route. One week post-infection after virus clearance, the females were mated with naïve adult males. Age-matched naïve females were also mated concurrently. At birth, pups born to either dengue-immune or naïve mothers were switched and nursed by naïve or dengue-immune mothers respectively (Fig 1). Control groups comprised of mice nursed by birth mothers were also included. All pups were breastfed by the respective mothers and were weaned out 21 days later. At 5 and 10 weeks of age, these mice were challenged with either 106 PFU (sub-lethal dose) or 107 PFU (lethal dose) of DENV2 via iv route and monitored for survival and bled at specific time point for viremia determination. The infected animals were monitored daily for clinical manifestations. The scoring system used was: 0: Healthy; 1: Ruffled fur; 2: Hunched back; 3: Diarrhoea; 4: Lethargic; 5: Moribund. Survival rate was derived from the number of mice that were euthanized at moribund stage as evidenced by severe diarrhoea and extreme lethargy as described previously [11]. Serum collection was performed at various time points after birth for antibody measurement, or at day 4 post-infection to measure virus titres by plaque assay.

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