GM-CSF DNA: An adjuvant for higher avidity IgG, rectal IgA, and increased protection against the acute phase of a SHIV-89.6P challenge by a DNA/MVA immunodeficiency virus vaccine

Abstract

Single intradermal or intramuscular inoculations of GM-CSF DNA with the DNA prime for a simian-human immunodeficiency virus (SHIV)-89.6 vaccine, which consists of DNA priming followed by modified vaccinia Ankara (MVA) boosting, increased protection of both the blood and intestines against the acute phase of an intrarectal SHIV-89.6P challenge. GM-CSF appeared to contribute to protection by enhancing two antibody responses: the avidity maturation of anti-Env IgG in blood (p=or<0.01) and the presence of long lasting anti-viral IgA in rectal secretions (p<0.01). The avidity of anti-Env IgG showed strong correlations with protection both pre and post challenge. Animals with the highest avidity anti-Env Ab had 1000-fold reductions in peak viremia over those with the lowest avidity anti-Env Ab. The enhanced IgA response was associated with the best protection, but did not achieve significance.

Preclinical Studies of Human Immunodeficiency Virus/AIDS Vaccines: Inverse Correlation between Avidity of Anti-Env Antibodies and Peak Postchallenge Viremia

“…Full-length Env antigens as well as the ADA gp120 Env were produced for binding and avidity assays using transient transfections of 293T cells with DNAs expressing VLPs or pseudovirions. Expressed Envs were captured onto enzyme-linked immunosorbent assay (ELISA) plates using concanavilin A (Vector Laboratories) (7,21). gp140 was expressed using MVA/ADA.gp140 (P. L. Earl and B. Moss, unpublished data) and purified as previously described (10).…”

“…The third and fourth groups were used to test the ability of granulocyte-macrophage colony-stimulating factor (GM-CSF) to enhance the immune responses elicited by the clade B vaccine expressing the higher level of the ADA Env and a clade C vaccine (IN3DNA/MVA71) expressing the CCR5-tropic 98IN02 Env. GM-CSF was used as an adjuvant because in earlier trials codelivery of GM-CSF had enhanced the breadth of the neutralizing activity and the avidity of the anti-Env Ab elicited by simian/human immunodeficiency virus 89.6 (SHIV-89.6) immunogens (28) (21).…”

Applications of immunochemistry in human health: advances in vaccinology and antibody design (IUPAC Technical Report)

“…A genetic adjuvant is a protein with adjuvant properties that is encoded by the pDNA and hence is co-expressed with the antigen, bolstering the immune response towards this antigen. Examples are IL-12 or IL-15, IL-28B, the use of granulocyte macrophage colonystimulating factor (GM-CSF) or high-mobility-group-protein B1 (HMGB1) [72][73][74][75][76][77][78][79][80][81][82][83][84].…”

HIV Envelope-Specific Antibody and Vaccine Efficacy

“…Several vaccine approaches have been evaluated in non-human primates for the ability to elicit viral-specific IgA antibodies at genital/rectal sites. These have included tonsillar immunizations with replication-defective SIV (Vagenas et al, 2009), administration of DNA vaccines intranasally or rectally, followed by boosting with MVA recombinants (Bertley et al, 2004;Wang et al, 2004), intradermal or intramuscular administrations of DNA vaccines together with GM-CSF DNA or CCL27 DNA as adjuvants (Lai et al, 2007;Kraynyak et al, 2010) vaginal delivery of trimeric HIV envelope together with Carbopol gel (Cranage et al, 2011), upper respiratory track immunization with replication-competent Ad-recombinants followed by intramuscular boosting with envelope protein (Florese et al, 2009;Hidajat et al, 2009;Xiao et al, 2010), and intramuscular plus intranasal immunization with a gp41 subunit vaccine delivered on virosomes (Bomsel et al, 2011). These have had varying degrees of success in consistently eliciting mucosal IgA antibodies.…”