Safety and immunogenicity of a parenterally administered rotavirus VP8 subunit vaccine in healthy adults.

Publication Type
Journal Article
Year of Publication
2015
Authors
Fix, Alan D; Harro, Clayton; McNeal, Monica; Dally, Len; Flores, Jorge; Robertson, George; Boslego, John W; Cryz, Stanley
Secondary
Vaccine
Volume
33
Start Page
3766
Pagination
3766-3772
Date Published
07/2015
Keywords
Adjuvants, Immunologic; Adolescent; Adult; Aluminum Hydroxide; Antibodies, Neutralizing; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Enzyme-Linked Immunosorbent Assay; Female; gastroenteritis; Healthy Volunteers; Humans; Immunoglobulin A; Immunoglobulin G; Injections, Intramuscular; lymphocytes; Male; Middle Aged; Neutralization Tests; Placebos; RNA-Binding Proteins; Rotavirus Infections; Rotavirus Vaccines; Treatment Outcome; Vaccines, Subunit; Viral Nonstructural Proteins; Young Adult
Abstract

BACKGROUND: The P2-VP8 subunit vaccine for the prevention of rotavirus gastroenteritis is comprised of a truncated VP8 subunit protein from the rotavirus Wa strain (G1[P8]) fused to the tetanus toxin P2 epitope, and adsorbed on aluminum hydroxide for intramuscular administration.

METHODS: Three groups of 16 adults were randomized to receive three injections of P2-VP8 (12) or placebo (4) at doses of 10, 30 or 60 μg of vaccine. IgG and IgA antibodies to P2-VP8 were assessed by ELISA in serum and lymphocyte supernatant (ALS). Serum samples were tested for neutralizing antibodies to homologous and heterologous strains of rotavirus.

RESULTS: The vaccine was well-tolerated. All vaccine recipients demonstrated significant IgA responses and all but one demonstrated IgG responses; in the 60 μg cohort, geometric mean titers (GMTs) rose 70- and 80-fold for IgA and IgG, respectively. Homologous neutralizing antibody responses were observed in about half of participants in all three dose cohorts; in the 60 μg cohort, GMTs against Wa rose from 128 to 992. Neutralizing antibody responses were robust to P[8] strains, moderate to P[4] strains and negligible to P[6] strains. ALS IgA responses were dose dependent.

CONCLUSIONS: The P2-VP8 subunit vaccine was well tolerated and evoked promising immune responses.

CLINICAL TRIALS REGISTRATION: NCT01764256.