Passive Immunisation of Children With Bovine Colostrum Containing Antibodies to Human Rotavirus

Davidson, Geoffrey P.; Daniels, Elaine; Nunan, H; Moore, Amelia; Whyte, P. B. D.; Franklin, Karen E.; McCloud, Philip; Moore, David

doi:10.1016/s0140-6736(89)90771-x

Cited by 169 publications

(108 citation statements)

References 19 publications

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“…Actually, oral administration of milk from RV-immunized dams protected suckling mice against challenge (34); protective activity was detected in both the anti-rotavirus IgA and IgG fractions, but IgA was more potent in vivo than IgG (34). The use of a milk concentrate prepared from rotavirus-hyperimmunized cows resulted in a significant reduction in the duration of viral excretion in infants hospitalized for acute rotavirus gastroenteritis (1,12,21). However, milk from dams immunized with VLP2/6 did not prevent diarrhea in suckling offspring (9), while milk from VLP2/6/7-vaccinated mothers was protective, indicating that sIgA directed at VP7, but not at VP6, could be implicated in mediating immune exclusion.…”

Section: Discussionmentioning

confidence: 99%

Rotavirus Anti-VP6 Secretory Immunoglobulin A Contributes to Protection via Intracellular Neutralization but Not via Immune Exclusion

Corthésy¹,

Benureau

Perrier³

et al. 2006

J Virol

114

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Immunoglobulin A (IgA) monoclonal antibodies (MAbs) directed at the conserved inner core protein VP6 of rotavirus, such as the IgA7D9 MAb, provide protective immunity in adult and suckling mice when delivered systemically. While these antibodies do not have traditional in vitro neutralizing activity, they could mediate their antiviral activity either by interfering with the viral replication cycle along the IgA secretory pathway or by acting at mucosal surfaces as secretory IgA and excluding virus from target enterocytes. We sought to determine the critical step at which antirotaviral activity was initiated by the IgA7D9 MAb. The IgA7D9 MAb appeared to directly interact with purified triple-layer viral particles, as shown by immunoprecipitation and immunoblotting. However, protection was not conferred by passively feeding mice with the secretory IgA7D9 MAb. This indicates that the secretory IgA7D9 MAb does not confer protection by supplying immune exclusion activity in vivo. We next evaluated the capacity of polymeric IgA7D9 MAb to neutralize rotavirus intracellularly during transcytosis. We found that when polymeric IgA7D9 MAb was applied to the basolateral pole of polarized Caco-2 intestinal cells, it significantly reduced viral replication and prevented the loss of barrier function induced by apical exposure of the cell monolayer to rotavirus, supporting the conclusion that the antibody carries out its antiviral activity intracellularly. These findings identify a mechanism whereby the well-conserved immunodominant VP6 protein can function as a target for heterotypic antibodies and protective immunity.Rotavirus (RV) is the main cause of severe diarrhea in young infants worldwide and is responsible for 611,000 deaths per year (36). Two vaccines based on attenuated live viruses have recently completed successful phase III clinical trials and showed efficacy in preventing severe RV diarrhea caused by multiple serotypes (45, 50). However, the relevant immune effectors required for achieving protection against diverse circulating strains are still a matter of considerable debate. While CD8 ϩ T cells facilitate the timely clearance of rotavirus infection, B cells with the appropriate pattern of mucosal homing receptors and antibody production have been demonstrated as crucial for protection from reinfection (17, 24).Neutralizing antibodies against RV that block viral replication in cell culture are felt to play a major role in defense. A variety of passive antibody transfer studies in animals (28), as well as immunization studies using selected rotavirus reassortants in humans (7), have demonstrated a clear role for VP4 and VP7 in protective immunity. Neutralizing antibodies are directed against the outer shell VP4 and VP7 proteins, whose variable antigenic specificities define multiple serotypes, assigned as P and G serotypes, respectively (41). Worldwide, the G1-to-G4 serotypes associated with P4 and P8 and the more recently described G9/P6 or P8 serotypes are globally important rotavirus G/P combinations in human...

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Section: Discussionmentioning

confidence: 99%

Rotavirus Anti-VP6 Secretory Immunoglobulin A Contributes to Protection via Intracellular Neutralization but Not via Immune Exclusion

Corthésy¹,

Benureau

Perrier³

et al. 2006

J Virol

114

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“…In clinical trials the oral administration of several different immunoglobulin preparations has revealed that it can survive passage through the gastrointestinal tract of bone marrow transplantation recipients 5 and has protective effects against infectious diarrhoea and necrotizing enterocolitis. [6][7][8][9] It may be anticipated that production and function of IgA in the gastro-intestinal tract is disrupted by the preparative regimen preceding BMT. The aim of this placebo-controlled, randomised trial was therefore to investigate whether the oral administration of an IgA-IgG preparation made from human serum would reduce gastro-intestinal toxicity or infectious complications related to autologous BMT.…”

mentioning

confidence: 99%

Gut mucosa barrier preservation by orally administered IgA-IgG to patients undergoing bone marrow transplantation: a randomised pilot study

Johansson

Ekman

1999

Bone Marrow Transplant

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Summary:Intensive cytotoxic therapy with bone-marrow transplantation (BMT) allows a potential cure for haematological malignancies. Protective strategies to minimise haematological toxicities have been successful and currently toxicity to the gastro-intestinal tract is the major cause of treatment-related morbidity and the dose-limiting factor that prevents further dose escalation. In a randomised, placebo-controlled trial we investigated whether an oral immunoglobulin preparation (IgA-IgG) can diminish intestinal toxicity with autologous BMT. IgA-IgG (n = 6) and placebo (n = 7) were orally administered from 1 day prior to the start until 1 week after the termination of the cytotoxic treatment (a total of 14 days). Intestinal toxicity was assessed by a 51 Cr-EDTA absorption test for intestinal permeability and by the clinical criteria laid down by the WHO for the period before the start of the cytotoxic treatment, 1 day prior to stem-cell infusion and 4, 7, 10 and 14 days after stemcell infusion. In the placebo group there was a significant increase in intestinal permeability on day 4 (P Ͻ 0.005) and on day 7 (P Ͻ 0.05) after stem-cell infusion, compared with the baseline, which was not seen for IgA-IgG. In addition, patients receiving IgAIgG had significantly less intestinal permeability on day 4 (P Ͻ 0.05) and on day 7 (P Ͻ 0.05), compared with the placebo group. No significant, positive effect as regards clinical toxicity was observed. Oral administration of IgA-IgG to patients undergoing intensive cytotoxic therapy prior to BMT seems to have a protective effect on the gut mucosa barrier which is normally disrupted by this therapy.

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“…Casein, a glycosylated protein, binds to the viral antigens directly using the glycosylated residue [33]. Vaccination of cows is a natural source of antibody production.…”

Section: Bovine Colostrum As Viral Therapeuticsmentioning

confidence: 99%

Broad Neutralizing Antibodies to HIV Env and Other Complex Viral Antigens from Vaccinated Cows

Heydarchi¹,

Quiroz²,

Purcell³

2016

J Vaccines Vaccin

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The idea of using antibodies to restrain HIV viral replication has been a growing interest since many years ago. HIV-patient serum with elite virus-neutralizing breadth has led to the preparation of broadly neutralizing antibodies (BrNAbs) with long and highly mutated CDRH3 domains that can neutralize a broad array of viral strains and prevent transmission in animal models. Recent advances have resulted in the discovery of BrNAbs that are more potent and can neutralize many HIV-1 subtypes. However, elicitation of these antibodies in infected individuals usually requires a long time of antigen exposure. Though BrNAbs are shown to be successful either therapeutically or prophylactically against HIV-1, production of these antibodies in bulk, commercial-sized batches are expensive and non-affordable particularly for poor countries. Therefore, more durable preventative or therapeutic strategies are required. Immunization of the cows with HIV Env is shown to be capable of producing 20 kg purified anti-HIV-1 BrNAbs and this amount could be sufficient for 2 million × 10 mg doses for formulation and pre-clinical testing as an HIV microbicide. In addition, bovine immunoglobulins typically have variable third heavy complementarity determining regions (CDRH3) that may potentially facilitate access to antigenic epitopes that are very difficult for other species to engage. Thus, cows could be engaged to elicit anti-HIV antibodies with the features of human BrNAbs and bovine colostrum could be a promising and cheap resource for the development of combination microbicides.

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Passive Immunisation of Children With Bovine Colostrum Containing Antibodies to Human Rotavirus

Cited by 169 publications

References 19 publications

Rotavirus Anti-VP6 Secretory Immunoglobulin A Contributes to Protection via Intracellular Neutralization but Not via Immune Exclusion

Rotavirus Anti-VP6 Secretory Immunoglobulin A Contributes to Protection via Intracellular Neutralization but Not via Immune Exclusion

Gut mucosa barrier preservation by orally administered IgA-IgG to patients undergoing bone marrow transplantation: a randomised pilot study

Broad Neutralizing Antibodies to HIV Env and Other Complex Viral Antigens from Vaccinated Cows

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