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1.
J Immunol ; 202(3): 799-804, 2019 02 01.
Article in English | MEDLINE | ID: mdl-30593536

ABSTRACT

Broadly neutralizing, anti-HIV-1 gp120 mAbs have been isolated from infected individuals, and there is considerable interest in developing these reagents for Ab-based immunoprophylaxis and treatment. As a means to identify potentially new anti-HIV Abs, we exploited humanized NOD-scid IL2rγnull mice systemically infected with HIV-1 to generate a wide variety of Ag-specific human mAbs. The Abs were encoded by a diverse range of variable gene families and Ig classes, including IgA, and several showed significant levels of somatic mutation. Moreover, the isolated Abs not only bound target Ags with similar affinity as broadly neutralizing Abs, they also demonstrated neutralizing ability against multiple HIV-1 clades. The use of humanized mice will allow us to use our knowledge of HIV-1 gp120 structure and function, and the immune response targeting this protein, to generate native human prophylactic Abs to reduce the infection and spread of HIV-1.


Subject(s)
Antibodies, Monoclonal, Humanized/genetics , HIV Antibodies/genetics , HIV Envelope Protein gp120/immunology , HIV-1/immunology , Animals , Animals, Genetically Modified , Antibodies, Monoclonal, Humanized/immunology , Antibodies, Neutralizing/genetics , Antibodies, Neutralizing/immunology , HIV Antibodies/immunology , HIV Infections/immunology , Humans , Mice , Mice, Inbred NOD , Mice, SCID , Neutralization Tests
2.
Vaccine ; 38(10): 2333-2339, 2020 02 28.
Article in English | MEDLINE | ID: mdl-32008877

ABSTRACT

Enterotoxigenic Escherichia coli (ETEC) is a leading cause of diarrhea-associated illness in developing countries. There is currently no vaccine licensed to prevent ETEC and the development of an efficacious prophylaxis would provide an intervention with significant impact. Recent studies suggested that effective protection could be achieved by inducing immunity to block colonization of ETEC. Here, we evaluated the efficacy of secretory (s) IgA2 and dimeric (d) IgA2 of an anti-colonization factor antigen antibody, 68-61, in the Aotus nancymaae nonhuman primate (NHP) ETEC challenge model via oral and parental delivery. Thirty-nine animals were distributed across 3 groups of 13, and challenged with 5.0x1011 colony forming unit (CFU) of H10407 on Day 0. Group 1 received a dIgA2 68-61 subcutaneously on day 0. Group 2 received a SIgA2 68-61 orally on days -1, 0, and +1, and Group 3 received an irrelevant SIgA2 antibody orally on days -1, 0, and +1. All animals were observed for symptoms of diarrhea, and stools were collected for ETEC colony counts. Anti-CfaE SIgA2 treatment significantly lowered the attack rate, resulting in a protective efficacy of 74.1% (p = 0.025) in Group 2 as compared to Group 3. The anti-CfaE dIgA2 treatment group had reduced diarrheal attack rate, although the reduction did not reach significance (57.1%; p = 0.072) as compared to the irrelevant SIgA2 Group 3. Our results demonstrated the feasibility of oral administration of SIgA as a potential immunoprophylaxis against enteric infections. To our knowledge, this is the first study to demonstrate the efficacy of administrated SIgA in a nonhuman primate model.


Subject(s)
Antibodies, Bacterial/administration & dosage , Diarrhea/prevention & control , Enterotoxigenic Escherichia coli , Escherichia coli Infections , Immunoglobulin A, Secretory/administration & dosage , Administration, Oral , Animals , Aotidae , Diarrhea/microbiology , Disease Models, Animal , Escherichia coli Infections/prevention & control
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