BACKGROUND: In some areas of the world, mother-to-child transmission of HIV remains a significant problem in part due to widespread breastfeeding, which is essential because of scarce supply of a safe replacement, protection conferred by breast milk against many enteric illnesses, and cultural norms. We propose that sustained adequate levels of protective antibodies in breast milk will prevent transmission of HIV. METHODS: The HIV-neutralizing human monoclonal antibody b12 (IgG1) has been expressed as an IgA2 in CHO cells and shown to retain full immunoreactivity and neutralizing activity as the parental IgG1. The expression plasmids containing the b12 heavy and light chains were also used to construct milk-specific expression vectors using the GTC goat β-casein expression vector to direct expression of linked genes to the mammary gland with subsequent secretion into the milk. Female transgenic mice were generated and following parturition, their milk was tested for antibody immunoreactivity with gp120 and neutralization of HIV. RESULTS: When milk-derived b12 IgA2 was compared with CHO-derived b12 IgA2 (or IgG1), immunoreactivity was retained. When tested for neutralization, milk-derived b12 IgA2 was at least comparable to CHO-derived antibody and in some cases, superior to CHO-derived antibody. Furthermore, milk that expressed b12 IgA2 was significantly more effective at mediating antibody-dependent cell killing. CONCLUSIONS: These results suggest that it is possible to achieve functional HIV-specific mAb in the milk of transgenic mice, and further investigations are warranted to explore ways for inducing this type of antibody response in the breast milk of HIV-infected women.
BACKGROUND: In some areas of the world, mother-to-child transmission of HIV remains a significant problem in part due to widespread breastfeeding, which is essential because of scarce supply of a safe replacement, protection conferred by breast milk against many enteric illnesses, and cultural norms. We propose that sustained adequate levels of protective antibodies in breast milk will prevent transmission of HIV. METHODS: The HIV-neutralizing human monoclonal antibody b12 (IgG1) has been expressed as an IgA2 in CHO cells and shown to retain full immunoreactivity and neutralizing activity as the parental IgG1. The expression plasmids containing the b12 heavy and light chains were also used to construct milk-specific expression vectors using the GTC goat β-casein expression vector to direct expression of linked genes to the mammary gland with subsequent secretion into the milk. Female transgenic mice were generated and following parturition, their milk was tested for antibody immunoreactivity with gp120 and neutralization of HIV. RESULTS: When milk-derived b12 IgA2 was compared with CHO-derived b12 IgA2 (or IgG1), immunoreactivity was retained. When tested for neutralization, milk-derived b12 IgA2 was at least comparable to CHO-derived antibody and in some cases, superior to CHO-derived antibody. Furthermore, milk that expressed b12 IgA2 was significantly more effective at mediating antibody-dependent cell killing. CONCLUSIONS: These results suggest that it is possible to achieve functional HIV-specific mAb in the milk of transgenic mice, and further investigations are warranted to explore ways for inducing this type of antibody response in the breast milk of HIV-infectedwomen.
Authors: J R Mascola; G Stiegler; T C VanCott; H Katinger; C B Carpenter; C E Hanson; H Beary; D Hayes; S S Frankel; D L Birx; M G Lewis Journal: Nat Med Date: 2000-02 Impact factor: 53.440
Authors: R Hofmann-Lehmann; J Vlasak; R A Rasmussen; B A Smith; T W Baba; V Liska; F Ferrantelli; D C Montefiori; H M McClure; D C Anderson; B J Bernacky; T A Rizvi; R Schmidt; L R Hill; M E Keeling; H Katinger; G Stiegler; L A Cavacini; M R Posner; T C Chou; J Andersen; R M Ruprecht Journal: J Virol Date: 2001-08 Impact factor: 5.103
Authors: R Hofmann-Lehmann; R A Rasmussen; J Vlasak; B A Smith; T W Baba; V Liska; D C Montefiori; H M McClure; D C Anderson; B J Bernacky; T A Rizvi; R Schmidt; L R Hill; M E Keeling; H Katinger; G Stiegler; M R Posner; L A Cavacini; T C Chou; R M Ruprecht Journal: J Med Primatol Date: 2001-08 Impact factor: 0.667
Authors: Xiping Wei; Julie M Decker; Hongmei Liu; Zee Zhang; Ramin B Arani; J Michael Kilby; Michael S Saag; Xiaoyun Wu; George M Shaw; John C Kappes Journal: Antimicrob Agents Chemother Date: 2002-06 Impact factor: 5.191
Authors: Xiaocong Yu; Mark Duval; Christopher Lewis; Melissa A Gawron; Rijian Wang; Marshall R Posner; Lisa A Cavacini Journal: J Immunol Date: 2012-11-26 Impact factor: 5.422