Effects of Antigen-Antibody Complexes on the Primary Immune Response in Rhesus Monkeys

Houston, William E.; Pedersen, Carl E.; Cole, Francis E.; Spertzel, Richard O.

doi:10.1128/iai.10.3.437-442.1974

Cited by 12 publications

(5 citation statements)

References 16 publications

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“…Neutralizing antibody to alphaviruses, either induced by immunization or passively administered, is known to protect a wide variety of animal species, including humans, against virulent alphavirus strains [Cole and McKinney, 1971 ;Houston et al, 1974;McKinney et al, 19631. While the mechanisms by which certain alphaviruses, such as Venezuelan equine encephalitis virus (VEE), are neutralized by antibody have been studied in some detail in vitro [Hahon, 19691, very little is known concerning the mechanisms of virus neutralization in the intact animal.…”

Section: Introductionmentioning

confidence: 99%

Opsonization of alphaviruses in hamsters

Jahrling

Hesse

Gangemi

1983

Journal of Medical Virology

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Immune elimination of alphaviruses in immunized hamsters appears to involve formation of virus/antibody aggregates which are subsequently cleared from the circulation by cells of the reticuloendothelial system (RES). Virulent strains of Venezuelan (VEE) and Western equine encephalitis (WEE) viruses which were cleared slowly from the circulation of nonimmune hamsters, were cleared rapidly when inoculated into the blood of immunized hamsters. Likewise, when these viruses were mixed with specific hamster immune serum prior to inoculation, they were efficiently cleared from the circulation of nonimmune hamsters. Virus, mixed with specific immune serum, or inoculated into immunized hamsters, formed virus/antibody aggregates, as demonstrated by density gradient centrifugation, filtration through polycarbonate membranes, precipitation with Staphylococcus protein A, and electron microscopy. Cleared virus was concentrated primarily in liver and spleen, as confirmed by autoradiography. Immune clearance of virulent VEE was demonstrable within 5 to 6 days following immunization of hamsters with live attenuated VEE vaccine, strain TC-83. In these hamsters, a close association was established between formation of virus/antibody aggregates, rapid clearance, and survival of challenged hamsters. Adsorption of virus to hamster macrophages in culture was enhanced by immune serum in the presence of complement. These results are compatible with the hypothesis that immune clearance of virus in the intact hamster involves a complement-dependent interaction of virus/antibody complexes with cells which possess Fc and complement receptors. The clearance of immune complexes by the RES serves to amplify the protective effect of neutralizing antibody alone.

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Section: Introductionmentioning

confidence: 99%

Opsonization of alphaviruses in hamsters

Jahrling

Hesse

Gangemi

1983

Journal of Medical Virology

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“…In comparison with live attenuated VEE virus vaccine, inactivated vaccine is weak-C a antigenic in rhesus monkeys (21). However, when poly(ICLC) was used in high doses (1 to 3 mg/ kg) as an adjuvant with the inactivated antigen, anibody titers in monkeys were comparable to those elicited to live attenuated VEE vaccine (19).…”

mentioning

confidence: 99%

Adjuvant Effects of Low Doses of a Nuclease-Resistant Derivative of Polyinosinic Acid · Polycytidylic Acid on Antibody Responses of Monkeys to Inactivated Venezuelan Equine Encephalomyelitis Virus Vaccine

et al. 1979

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Polyriboinosinic·polyribocytidylic acid [poly(I)·poly(C)] stabilized with poly- l -lysine and carboxymethylcellulose [poly(ICLC)] has been previously shown to be a compound with marked adjuvant activity when given in high doses with inactivated Venezuelan equine encephalomyelitis (VEE) virus vaccine. This study investigated the effects of much lower doses of poly(ICLC) on the magnitude and kinetics of the primary and secondary humoral antibody responses of rhesus monkeys to inactivated VEE virus vaccine. Monkeys given a single injection of vaccine developed very low neutralizing antibody titers, whereas those given adjuvant plus vaccine had 30- to 100-fold-higher titers which remained elevated for longer than 6 months. Low doses of poly(ICLC) given with VEE virus vaccine resulted in a profound but transient increase in priming of secondary antibody responses to the antigen. In contrast, the administration of poly- l -lysine and carboxymethylcellulose alone without the poly(I)·poly(C) component of the complex had no adjuvant effect on antibody responses of monkeys to VEE virus vaccine. The temporal development of antibody by class (immunoglobulin M-immunoglobulin G) in monkeys given two injections of adjuvant-vaccine was not different from that with vaccine alone. Serial hematological and clinical chemistry determinations on monkeys given single or multiple doses of poly(ICLC) with vaccine were not different from values in monkeys given vaccine alone.

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“…We reasoned that if the stabilization process resulted in a greater capacity for PICLC to induce interferon in primates, perhaps the stabilized drug would also potentiate a primary antibody response in rhesus monkeys given a virus vaccine without the aid of an additional adjuvant. Formalin-inactivated Venezuelan equine encephalomyelitis virus vaccine (IVEE) (1), which produces only a moderate primary antibody response in rhesus monkeys (5), was used as the antigen in this study. Vaccine (0.5 ml) was combined just prior to subcutaneous immunization with an appropriate dilution of PICLC (6) (lot no.…”

mentioning

confidence: 99%

“…49, 2 mg/ml) so that doses of 1 or 3 mg per kg of body weight were administered once to groups containing four rhesus (Macaca mulatta) monkeys each. Serum taken from monkeys in each group, along with a vaccine control group, was tested at regular intervals following immunization for the presence of plaque reduction neutralizing antibody to VEE virus by a method previously described (5).…”

mentioning

confidence: 99%

Modified polyriboinosinic-polyribocytidylic acid, an immunological adjuvant

Houston¹,

Crabbs²,

Stephen³

et al. 1976

Infect Immun

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Stabilization of polyriboinosinic-polyribocytidylic acid against enzymatic hydrolysis by addition of poly-1-lysine and carboxymethylcellulose (PICLC) resulted in a compound with marked adjuvanticity. The primary antibody response of rhesus monkeys to formalin-inactivated Venezuelan equine encephalomyelitis virus vaccine was significantly potentiated if the vaccine was combined with PICLC prior to vaccination. The antibody response was maintained at a significantly higher level than controls for 2.5 months postvaccination and paralleled immunological responses reported for live, attenuated (TC-83) vaccine.

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Effects of Antigen-Antibody Complexes on the Primary Immune Response in Rhesus Monkeys

Cited by 12 publications

References 16 publications

Opsonization of alphaviruses in hamsters

Opsonization of alphaviruses in hamsters

Adjuvant Effects of Low Doses of a Nuclease-Resistant Derivative of Polyinosinic Acid · Polycytidylic Acid on Antibody Responses of Monkeys to Inactivated Venezuelan Equine Encephalomyelitis Virus Vaccine

Modified polyriboinosinic-polyribocytidylic acid, an immunological adjuvant

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