Alan D Fix1, Clayton Harro2, Monica McNeal3, Len Dally4, Jorge Flores5, George Robertson6, John W Boslego7, Stanley Cryz8. 1. Vaccine Development Global Program, PATH, 455 Massachusetts Ave., Suite 1000, Washington, DC, 20001, USA. Electronic address: afix@path.org. 2. Center for Immunization Research, Department of International Health, The Johns Hopkins Bloomberg School of Public Health, 624N. Broadway, Suite 117, Hampton House, Baltimore, MD 21205, USA. 3. Laboratory for Specialized Clinical Studies, Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, 333 Burnet Avenue ML6014, Cincinnati, OH, 45229, USA. Electronic address: Monica.McNeal@cchmc.org. 4. The EMMES Corporation, 401N. Washington Street, Suite 700, Rockville, MD, 20850, USA. Electronic address: ldally@emmes.com. 5. Vaccine Development Global Program, PATH, 455 Massachusetts Ave., Suite 1000, Washington, DC, 20001, USA. Electronic address: jeflores@path.org. 6. Vaccine Development Global Program, PATH, 455 Massachusetts Ave., Suite 1000, Washington, DC, 20001, USA. Electronic address: grobertson@path.org. 7. Vaccine Development Global Program, PATH, 455 Massachusetts Ave., Suite 1000, Washington, DC, 20001, USA. Electronic address: jboslego@path.org. 8. Vaccine Development Global Program, PATH, 455 Massachusetts Ave., Suite 1000, Washington, DC, 20001, USA. Electronic address: scryz@path.org.
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.
RCT Entities:
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.
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