Conference Abstracts

Session 9: Rotavirus

Development of candidate rotavirus vaccines

Ruth Bishop Department of Gastroenterology, Royal Children's 3052, Australia

Rotaviruses are the single most important cause of severe diarrhoea in young children throughout the world. Primary infection does not appear to produce immunity to reinfection, but to protect against development of severe disease on reinfection. Candidate rotavirus vaccines tested to date have been developed using a 'Jennerian' approach. Strains of bovine and simian rotaviruses that are naturally attenuated for humans have been trialled and found to confer immunity that is serotype

Hospital, Parkville, Victoria

specific. The spectrum of protection has been widened by developing reassortants in which the bovine or simian gene coding for VP7 (the major outer capsid protein) has been replaced by the corresponding gene from human VP7 types 1, 2 and 4. Once the protective antigen(s) are identified it may be possible to develop subunit vaccines that eliminate side effects sometimes observed with live vaccine candidates.

Evaluation of attenuated rotavirus (RV) vaccines for the prevention of severe diarrhea in infants and young children

A.Z. Kapikian 1, J. Flores 1, K.Y. Green 1, Y. Hoshino 1, M. Gorziglia 1, 1 2 3 4 5 R.M. Chanock . T. Vesikari , H.P. Madore , K. Midthun , B. Davidson ,

I. Perez-Schael 6" 1 2 National Institutes of Health, Bethesda, MD, USA; University of Tampere, Tam_pere, Finland; 3University of Rochester, Rochester, NY," 4johns Hopkins

5 University, Baltimore, USA," Wyeth-Ayerst Research, Philadelphia, PA, USA; 6Central University of Venezuela, Caracas, Venezuela

There is a critical need for a RV vaccine that can prevent severe RV diarrhea during the first two years of life. The 'Jennerian' approach to vaccination in which an antigenically related strain derived from a non-human host is used as immunogen has had only limited success because serotype-specific immunity against all 4 epidemiologically important VP7 serotypes could not be achieved consistently (using bovine or simian RV) in infants < 6 months of age who had not undergone prior natural RV infection. Thus, a modified Jennerian approach has been adopted in which 4 strains comprised of (a) RRV (VP7 serotype

3) or (b) 3 human RV-RRV reassortants each containing 10 RRV genes and a single human RV gene that encodes VP7 serotype 1, 2 or 4 specificity are combined into a quadrivalent vaccine. Study of human RV-bovine RV (UK) reassortants is also underway. If the modified Jennerian approach (which emphasizes the role of VP7) does not yield adequate protection, other avenues which take advantage of both the VP7 and VP4 specificities of human RV may-be needed, and are thus under study.

Safety, immunogenicity and efficacy of one dose of the Rhesus and serotype 1 and 2 human-rhesus reassortant rotavirus vaccines

C.F. Lanata, R.E. Black, J. Flores, A. Kapikian Instituto de Investigacion Nutricional, AP 18-0191, Lima, Peru; Johns Hopkins University School of Public Health and National Institutes of Health, Baltimore, MD, USA

One dose of 104 pfu of either Rhesus (RRV), serotype 1 reassortant (DxRRV) and serotype 2 reassortant (DSlxRRV) rotavirus vaccines or placebo were administered with buffer at 2 months of age in 800 Peruvian children. Twice a day home surveillance by trained field workers for 7 consecutive days revealed that 13% of RRV recipients had at least one rectal temperature >38C vs 7-9% in placebo or other vaccine recipients. There was no increase in diarrhea or other side effects. Seroresponse was analyzed by IgA ELISA; DxRRV (50%), RRV (50%) and DSlxRRV (70%) vs 18% in placebo recipients. Vaccine efficacy was evaluated by twice weekly home

surveillance for diarrheal illness. Identified diarrheal episodes were cultured and rotavirus identified by ELISA. Preliminary analysis showed that after 2 years of surveillance RRV had a 30% efficacy against any rotavirus illness. DxRRV provided 49% protection against rotavirus illness requiring visits to health facilities. Preliminary analysis suggest that serotype- specific seroresponse was highly protective and that vaccine failures occurred in children who did not seroconvert. Serotype-specific immune responses and final analysis of serotype-specific vaccine efficacy will be presented.

272 Vaccine, Vol. 10, Issue 4, 1992