Summary
Synopsis
Tetravalent human- rhesus reassortant rotavirus vaccine (RRV- TV) contains the rhesus rotavirus (RRV) strain MMU 18006, which has serotype G3 specificity, and reassortant rotavirus strains with human serotype G1, G2 and G4 specificity. Rotavirus gastroenteritis in humans is predominantly caused by these 4 serotypes.
RRV- TV 4 × 104, 4 × 105 or 4 × 106 plaque- forming units (PFU) per dose induces seroresponse rates (generally defined as a ≥ 4- fold increase in antibody titre) of 48 to 93% for IgA against RRV and 49 to 90% for neutralising antibodies to RRV after 1 to 3 doses in infants aged ≥ 4 weeks. Seroresponse rates for neutralising antibodies to human serotypes G1, G2, G3 and G4 are generally lower (2 to 68%). The rates generally increase with sequential doses, but not necessarily with increased vaccine titre. Seroresponse rates appear to be better in older infants than in neonates or infants aged ≤ 12 weeks.
RRV- TV is more immunogenic against human G2, G3 and G4 serotypes than the monovalent serotype G1 human- rhesus reassortant rotavirus vaccine (RRV- S1) and tends to be more immunogenic against G1, G2 and G3 serotypes than the human serotype G1 strain vaccine M37.
In most settings, RRV- TV has at least moderate efficacy in reducing the incidence of rotavirus gastroenteritis. Importantly, it protects against severe disease, with efficacy rates of 69 to 100% against very severe rotavirus gastroenteritis in large scale studies in the US, Finland and Venezuela. RRV- TV has similar overall efficacy to RRV- S1, but provides greater protection against gastroenteritis caused by rotavirus strains of serotypes other than G1. The efficacy of RRV- TV is not significantly affected by breast feeding or concurrent use of oral poliovirus vaccine.
The only adverse effect with which RRV- TV has been associated is a mild, transient febrile reaction.
Limited data from the US and Finland suggest that vaccination with RRV- TV could be cost saving.
In conclusion, the incidence of paediatric rotavirus gastroenteritis, particularly severe cases, would be reduced in most settings by the incorporation of RRV- TV into routine childhood immunisation schedules. Further refinements to RRV- TV (and/or development of additional candidate vaccines) may eventually produce even greater protective efficacy. In the meantime, RRV- TV is a significant advance in the prevention of paediatric rotavirus gastroenteritis worldwide.
Overview of Rotavirus Infection
Rotavirus is a double-stranded RNA virus. Human rotavirus gastroenteritis is most commonly caused by group A rotaviruses. Worldwide, the most prevalent glycoprotein antigen-determined (G) serotypes are G1, G2, G3 and G4.
The virus is highly infectious, with transmission occurring primarily via the faecal-oral route. Infection is largely limited to the small intestine. Almost all children are infected with rotavirus by the age of 3 to 5 years, and it is the most common causal agent of severe life-threatening diarrhoea in children and infants worldwide. Dehydration and electrolyte imbalance associated with rotavirus gastroenteritis cause significant mortality in developing countries (more than 800 000 children die each year) and the disease is responsible for a large number of hospitalisations in developed countries. Symptomatic illness occurs most commonly in infants aged ≈3 months to 2 years.
Immunogenicity
Tetravalent human-rhesus reassortant rotavirus vaccine (RRV-TV) is composed of the rhesus rotavirus (RRV) strain MMU 18006, which shares neutralisation specificity with human rotavirus serotype G3, and 3 reassortant strains with human serotype G1, G2 or G4 specificity.
In immunogenicity trials in healthy infants aged ≥4 weeks, the seroresponse rate (generally defined as a ≥4-fold increase in antibody titre) for IgA against RRV was 48 to 93% (median 74%) after 1 to 3 doses of RRV-TV 4 × 104, 4 × 105 or 4 × 10 plaque-forming units (PFU) per dose. The seroresponse rate was significantly higher than after placebo (0 to 33%; median 11%). For neutralising antibody assays, the greatest seroresponse rates in RRV-TV recipients were to RRV (49 to 90%), whereas those to human serotypes Gl, G2, G3 and G4 were lower (2 to 68%). Seroresponse rates to RRV-TV were generally higher after 3 doses than after 1 dose. However, increasing the titre of vaccine dose (rather than the number of doses) was not consistently shown to increase seroresponse rates. RRV-TV 4×10 or 4×105 PFU was only moderately immunogenic in neonates, and the seroresponse rate was significantly greater in infants aged 16 to 24 weeks than in those aged 6 to 12 weeks in one study in which infants received a single dose of RRV-TV 4 × 105 or 4 × 106 PFU.
Breast feeding did not significantly reduce the immunogenicity of the vaccine in infants aged ≥4 weeks. RRV-TV does not significantly interfere with the immunogenicity of oral poliovirus vaccine (OPV), although a slight reduction in the response to poliovirus serotype 1 has been reported. The IgA seroresponse to RRV is reduced by concurrent use of OPV but the effect does not appear to be clinically significant when 3 doses of RRV-TV are given. Administration of a buffer to prevent inactivation of the acid-labile vaccine is required for the immunogenicity of RRV-TV to be optimal.
RRV-TV (3 doses of 4 × 104 or 4 × 105 PFU/dose) induced similar seroresponse rates for IgA against RRV to those induced by monovalent serotype Gl human-rhesus reassortant rotavirus vaccine (RRV-S1; 3 doses of 4 × 104 or 4 × 10 PFU/dose). However, RRV-TV generally had greater immunogenicity than RRV-S1 against serotype G2, G3 and G4 human rotavirus strains, whereas RRV-S1 had greater immunogenicity against serotype G1. Compared with the human serotype Gl strain vaccine M37 (1 dose of 1 × 104 PFU/dose or 2 doses of 1 × 105 PFU/dose), RRV-TV (1 or 2 doses of 4 × 104 or 4 × 105 PFU/dose) tended to induce higher seroresponse rates for IgA against RRV and for neutralising antibodies to human serotypes G1, G2 and G3.
Protective Efficacy
Data on the efficacy of RRV-TV in preventing paediatric rotavirus gastroenteritis are available from 7 trials involving 8720 infants aged 1 to 6 months from 5 countries. A 3-dose schedule of RRV-TV 4 × 104 PFU/dose in the US and 4 × 105 PFU/dose in the US, Finland and Venezuela reduced the incidence of rotavirus gastroenteritis by 48 to 68% compared with placebo. However, when used at the lower dosage (4 × 10 PFU/dose) the vaccine had a relative efficacy of only 35% in Brazil, and was not significantly protective in Peru. Efficacy was most evident in the first year after vaccination in all studies in which this was analysed.
The vaccine has greater efficacy against more severe disease. In large US, Finnish and Venezuelan studies, the relative efficacy rate of RRV-TV compared with placebo was 69 to 100% for the most severe rotavirus gastroenteritis. Vaccination provided 100% protection against rotavirus gastroenteritis-associated hospitalisation in Finland, and 70% protection in Venezuela. RRV-TV was associated with a reduction in health service use. Some studies showed a marked reduction in dehydrating rotavirus illness. The efficacy of RRV-TV was not significantly reduced by breast feeding or concurrent administration of OPV.
RRV-TV had similar overall efficacy to RRV-S1. However, RRV-TV was more effective than RRV-S 1 against rotavirus gastroenteritis caused by serotypes other than G1.
Pharmacoeconomic Considerations
Depending on the cost of the vaccine and its administration, the introduction of RRV-TV into routine childhood immunisation schedules could be cost saving, according to US and Finnish data. One US cost-effectiveness analysis calculated that the introduction of RRV-TV at $US30 (1993 US dollars) per dose would produce an annual saving of $US79 million ($US78 per case prevented) for the healthcare system and a saving of $US466 million ($US459 per case prevented) for society. Another analysis calculated that RRV-TV reduces the median expected societal cost of rotavirus gastroenteritis by $US11 (1992 US dollars) per infant, and would thus be cost saving provided that the vaccine cost less than this amount. A similar Finnish analysis calculated that RRV-TV reduces costs associated with rotavirus gastroenteritis by 109 Finnish marks (currency year not stated) per infant.
Tolerability
RRV-TV is generally well tolerated at doses of 4 × 10, 4 × 105 or 4 × 106 PFU/dose, but causes a higher incidence of fever (rectal or axillary temperature >38°C) than placebo. The febrile reaction is normally mild (≤39°C) and transient, occurring 3 to 5 days after vaccination and lasting 1 to 2 days. The incidence of fever is not dose related. However, it appears to occur more commonly after the first dose than after subsequent doses, and in older (age 16 to 24 weeks) rather than younger (age 6 to 12 weeks) infants. RRV-TV tended to be associated with a higher incidence of fever than RRV-S 1 or M37.
Dosage and Administration
Clinical trial data suggest that ideally a 3-dose schedule of RRV-TV 4 × 105 PFU/dose should be administered to infants between 2 and 7 months of age. RRV-TV can be administered concurrently with other injectable vaccines, but confirmation that there is no clinically significant interference between RRV-TV and OPV is required. Buffering is required to prevent inactivation of the vaccine.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Institute of Medicine. The prospects for immunizing against rotavirus. In: New Vaccine Development. Establishing priorities. Diseases of importance in developing countries. Vol II. Washington, DC: National Academy Press, 1986: 308–18
Dennehy PH, Rodgers Jr GC, Ward RL, et al. Comparative evaluation of reactogenicity and immunogenicity of two dosages of oral tetravalent rhesus rotavirus vaccine. Pediatr Infect Dis J 1996 Nov; 15: 1012–8
Estes MK. Advances in molecular biology: impact on rotavirus vaccine development. J Infect Dis 1996 Sep; 174Suppl. 1: S37–46
Christensen ML. Human viral gastroenteritis. Clin Microbiol Rev 1989 Jan; 2(1): 51–67
Blacklow NR, Greenberg HB. Viral Gastroenteritis. N Engl J Med 1991 Jul 25; 325(4): 252–64
Offit PA, Clark HE. Rotavirus. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases. 4th ed. Vol 2. New York: Churchill Livingstone, 1995: 1448–55
Glass RI, Kilgore PE, Holman RC, et al. The epidemiology of rotavirus diarrhea in the United States: surveillance and estimates of disease burden. J Infect Dis 1996; 174Suppl. 1: S5–S11
Gentsch JR, Woods PA, Ramachandran M, et al. Review of G and P typing results from a global collection of rotavirus strains: implications for vaccine development. J Infect Dis 1996; 174Suppl. 1: S30–6
Barnes GL, Bishop RF. Rotavirus infection and prevention. Curr Opin Pediatr 1997 Feb; 9: 19–23
Gerna G, Sarasini A, Zentilin L, et al. Isolation in Europe of 69 M-like (serotype 8) human rotavirus strains with either subgroup I or II specificity and a long RNA electropherotype. Arch Virol 1990; 112: 27–40
Ward RL. Mechanisms of protection against rotavirus in humans and mice. J Infect Dis 1996 Sep; 174Suppl. 1: S51–8
Offit PA. Host factors associated with protection against rotavirus disease: the skies are clearing. J Infect Dis 1996; 174Suppl. 1: S59–64
Greenberg HB, Clark HF, Offit PA. Rotavirus pathology and pathophysiology. Curr Top Microbiol Immunol 1994; 185: 255–83
Ball JM, Tian P, Zeng CQ-Y, et al. Age-dependent diarrhea induced by a rotaviral nonstructural glycoprotein. Science 1996 Apr 5; 272: 101–4
Kapikian AZ, Flores J, Hoshino Y, et al. Rotavirus: the major etiologic agent of severe infantile diarrhea may be controllable by a ‘Jennerian’ approach to vaccination. J Infect Dis 1986; 153(5): 815–22
Kapikian AZ, Chancock RM. Rotaviruses. In: Fields BN, Knipe DM, Howley PM, et al., editors. Fields virology. 3rd ed. Vol 2. Philadelphia: Lippincott-Raven, 1996: 1657–705
Isolauri E, Kaila M, Mykkänen H, et al. Oral bacteriotherapy for viral gastroenteritis. Dig Dis Sci 1994 Dec; 39(12): 2595–600
Guarino A, Canani RB, Russo S. Development in the treatment of rotaviral gastroenteritis: oral therapy with immunoglobulins and prospects for a vaccine. Clin Immunother 1995 Jun; 3: 476–84
Ho M-S, Glass RI, Pinsky PF, et al. Rotavirus as a cause of diarrheal morbidity and mortality in the United States. J Infect Dis 1988 Nov; 158(5): 1112–6
Matson DO, Estes MK. Impact of rotavirus infection at a large pediatric hospital. J Infect Dis 1990 Sep; 162: 598–604
Smith JC, Haddix AC, Teutsch SM. Cost-effectiveness analysis of a rotavirus immunization program for the United States. Pediatrics 1995 Oct; 96: 609–15
Ryan MJ, Ramsay M, Brown D, et al. Hospital admissions attributable to rotavirus infection in England and Wales. J Infect Dis 1996; 174Suppl. 1: S12–8
Pérez-Schael I. The impact of rotavirus disease in Venezuela. J Infect Dis 1996; 174Suppl. 1: S19–21
Perez-Schael I, Garcia D, Gonzalez M, et al. Prospective study of diarrheal diseases in Venezuelan children to evaluate the efficacy of rhesus rotavirus vaccine. J Med Virol 1990 Mar; 30: 219–29
LeBaron CW, Lew J, Glass RI, et al. Annual rotavirus epidemic patterns in North America. Results of a 5-year retrospective survey of 88 centers in Canada, Mexico and the United States. JAMA 1990 Aug 22/29; 264(8): 983–8
Cook SM, Glass RI, LeBaron CW, et al. Global seasonality of rotavirus infections. Bull World Health Organ 1990; 68(2): 171–7
Kapikian AZ, Hoshino Y, Chanock RM, et al. Efficacy of a quadrivalent rhesus rotavirus-based human rotavirus vaccine aimed at preventing severe rotavirus diarrhea in infants and young children. J Infect Dis 1996 Sep; 174Suppl. 1: S65–72
Midthun K, Greenberg HB, Hoshino Y, et al. Reassortant rotaviruses as potential live rotavirus vaccine candidates. J Virol 1985 Mar; 53(3): 949–54
Glass RI, Lang DR, Ivanoff BN, et al. Rotavirus — from basic research to a vaccine. J Infect Dis 1996 Sep; 174Suppl. 1: S1–2
Ward RL, Bernstein DI, Us RVEG. Lack of correlation between serum rotavirus antibody titers and protection following vaccination with reassortant RRV vaccines. Vaccine 1995 Sep; 13: 1226–32
Ward RL, Knowlton DR, Zito ET, et al. Serologie correlates of immunity in a tetravalent reassortant rotavirus vaccine trial. J Infect Dis 1997 Sep; 176: 570–7
Perez-Schael I, Blanco M, Vilar M, et al. Clinical studies of a quadrivalent rotavirus vaccine in Venezuelan infants. J Clin Microbiol 1990 Mar; 28: 553–8
Flores J, Perez-Schael I, Blanco M, et al. Reactogenicity and immunogenicity of a high-titer rhesus rotavirus-based quadrivalent rotavirus vaccine. J Clin Microbiol 1993 Sep; 31: 2439–45
Joensuu J, Koskenniemi E, Pang X-L, et al. Randomised placebo-controlled trial of rhesus-human reassortant rotavirus vaccine for prevention of severe rotavirus gastroenteritis. Lancet 1997 Oct 25; 350: 1205–9
Lanata CF, Midthun K, Black RE, et al. Safety, immunogenicity, and protective efficacy of one and three doses of the tetravalent rhesus rotavirus vaccine in infants in Lima, Peru. J Infect Dis 1996 Aug; 174: 268–75
Linhares AC, Gabbay YB, Mascarenhas JD, et al. Immunogenicity, safety and efficacy of tetravalent rhesus-human, reassortant rotavirus vaccine in Belém, Brazil. Bull World Health Organ 1996; 74: 491–500
Pérez-Schael I, Gutinas MJ, Pérez M, et al. Efficacy of the rhesus rotavirus-based quadrivalent vaccine in infants and young children in Venezuela. N Engl J Med 1997 Oct 23; 337(17): 1181–7
Simasathien S, Migasena S, Samakoses R, et al. Vaccination of Thai infants with rhesus-human reassortant tetravalent oral rotavirus vaccine. Pediatr Infect Dis J 1994 Jul; 13: 590–6
Bernstein DI, Glass RI, Rodgers G, et al. Evaluation of rhesus rotavirus monovalent and tetravalent reassortant vaccines in US children. JAMA 1995 Apr 19; 273: 1191–6
Rennels MB, Glass RI, Dennehy PH, et al. Safety and efficacy of high-dose rhesus-human reassortant rotavirus vaccines —report of the National Multicenter Trial. Pediatrics 1996 Jan; 97: 7–13
Santosham M, Moulton LH, Reid R, et al. Efficacy and safety of high-dose rhesus-human reassortant rotavirus vaccine in Native American populations. J Pediatr 1997 Oct; 131(4): 632–8
Flores J, Perez-Schael I, Blanco M, et al. Comparison of reactogenicity and antigenicity of M37 rotavirus vaccine and rhesus-rotavirus-based quadrivalent vaccine. Lancet 1990 Aug 11; 336: 330–4
Perez-Schael I, Blanco M, Garcia D, et al. Evaluation of the antigenicity and reactogenicity of varying formulations of the rhesus rotavirus-based quadrivalent and the M37 rotavirus vaccine candidates. J Med Virol 1994 Apr; 42: 330–7
Ceyhan M, Kanra G, Seçmeer G, et al. Take of rhesus-human reassortant tetravalent rotavirus vaccine in breast-fed infants. Acta Paediatr 1993 Mar; 82: 223–7
Dagan R, Kassis I, Sarov B, et al. Safety and immunogenicity of oral tetravalent human-rhesus reassortant rotavirus vaccine in neonates. Pediatr Infect Dis J 1992 Dec; 11: 991–6
Dagan R, Segal B, Kassis I, et al. Safety and immunogenicity of oral rhesus rotavirus tetravalent vaccine (ORRTV) in neonates: comparison of two doses [abstract no. 1096]. 31st Interscience Conference on Antimicrobial Agents and Chemotherapy; 1991 Sep 29–Oct 2; Chicago (IL), 281
Friedman MG, Segal B, Zedaka R, et al. Serum and salivary responses to oral tetravalent reassortant rotavirus vaccine in newborns. Clin Exp Immunol 1993; 92(2): 194–9
Rennels MB, Wasserman SS, Glass RI. Comparison of immunogenicity and efficacy of rhesus rotavirus reassortant vaccines in breastfed and nonbreastfed children. Pediatrics 1995 Dec; 96: 1132–6
Ing DJ, Glass RA, Woods PA, et al. Immunogenicity of tetravalent rhesus rotavirus vaccine administered with buffer and oral polio vaccine. Am J Dis Child 1991 Aug; 145: 892–7
Migasena S, Simasathien S, Samakoses R, et al. Simultaneous administration of oral rhesus-human reassortant tetravalent (RRV-TV) rotavirus vaccine and oral poliovirus vaccine (OPV) in Thai infants. Vaccine 1995 Feb; 13: 168–74
Rennels MB, Ward RL, Mack ME, et al. Concurrent oral poliovirus and rhesus-human reassortant rotavirus vaccination: effects on immune responses to both vaccines and on efficacy of rotavirus vaccines. J Infect Dis 1996 Feb; 173: 306–13
Pichichero ME, Marsocci SM, Francis AB, et al. Acomparative evaluation of the safety and immunogenicity of a single dose of unbuffered oral rhesus rotavirus serotype 3, rhesus/human reassortant serotypes 1, 2 and 4 and combined (tetravalent) vaccines in healthy infants. Vaccine 1993 May; 11: 747–53
Wright PF, King J, Araki K, et al. Simultaneous administration of two human-rhesus rotavirus reassortant strains of VP7 serotype 1 and 2 specificity to infants and young children. J Infect Dis 1991 Aug; 164: 271–6
Vesikari T, Varis T, Green K, et al. Immunogenicity and safety of rhesus human rotavirus reassortant vaccines with serotype 1 or 2 VP7 specificity. Vaccine 1991 May; 9: 334–9
Flores J, Perez-Schael I, Gonzalez M, et al. Protection against severe rotavirus diarrhoea by rhesus rotavirus vaccine in Venezuelan infants. Lancet 1987 Apr 18; I: 882–4
Keusch GT, Cash RA. A vaccine against rotavirus — when is too much too much? N Engl J Med 1997 Oct 23; 337(17): 1228–9
Black RE, Merson MH, Huq I, et al. Incidence and severity of rotavirus and Escherichia Coli diarrhoea in rural Bangladesh. Implications for vaccine development. Lancet 1981 Jan 17; I: 141–3
Griffiths RI, Anderson GF, Powe NR, et al. Economic impact of immunization against rotavirus gastroenteritis: evidence from a clinical trial. Arch Pediatr Adolesc Med 1995 Apr; 149: 407–14
Takala AK, Koskenniemi E, Joensuu J, et al. Economic evaluation of rotavirus vaccination in Finland [abstract no. 420]. Clin Infect Dis 1997 Aug; 25: 432
Uhnoo I, Riepenhoff-Talty M, Dharakul T, et al. Extramucosal spread and development of hepatitis in immunodeficient and normal mice infected with rhesus rotavirus. J Virol 1990 Jan; 64(1): 361–8
Gothefors L, Wadell G, Juto P, et al. Prolonged efficacy of rhesus rotavirus vaccine in Swedish children. J Infect Dis 1989 Apr; 159: 753–7
Mutz ID, Krainer F, Deutsch J, et al. A trial of RIT-4237 rotavirus vaccine in 1-month-old infants. Eur J Pediatr 1989 Jun; 148: 634–5
Vesikari T, Ruuska T, Delem A, et al. Efficacy of two doses of RIT 4237 bovine rotavirus vaccine for prevention of rotavirus diarrhoea. Acta Paediatr Scand 1991; 80: 173–80
Vesikari T. Clinical trials of live oral rotavirus vaccines: the Finnish experience. Vaccine 1993; 11(2): 255–61
Clark HF, Borian FE, Bell LM, et al. Protective effect of WC3 vaccine against rotavirus diarrhea in infants during a predom- inantly serotype 1 rotavirus season. J Infect Dis 1988; 158(3): 570–87
Vesikari T, Isolauri E, D’hondt E, et al. Protection of infants against rotavirus diarrhoea by RIT 4237 attenuated bovine rotavirus strain vaccine. Lancet 1984 May 5; I: 977–80
Lanata CF, Black RE, del Aguila R, et al. Protection of Peruvian children against rotavirus diarrhea of specific serotypes by one, two, or three doses of the RIT 4237 attenuated bovine rotavirus vaccine. J Infect Dis 1989 Mar; 159(3): 452–9
Bernstein DI, Smith VE, Sander DS, et al. Evaluation of WC3 rotavirus vaccine and correlates of protection in healthy infants. J Infect Dis 1990; 162(5): 1055–62
De Mol P, Zissis G, Butzler J-P, et al. Failure of live, attenuated oral rotavirus vaccine [letter]. Lancet 1986 Jul 12; II: 108
Georges-Courbot MC, Monges J, Siopathis MR, et al. Evaluation of the efficacy of a low-passage bovine rotavirus (strain WC3) vaccine in children in Central Africa. Res Virol 1991; 142: 405–11
Rennels MB, Losonsky GA, Young AE, et al. An efficacy trial of the rhesus rotavirus vaccine in Maryland. Am J Dis Child 1990 May; 144: 601–4
Santosham M, Letson WG, Wolff M, et al. A field study of the safety and efficacy of two candidate rotavirus vaccines in a Native American population. J Infect Dis 1991; 163: 483–7
Senturia YD, Peckham CS, Cordery M, et al. Live attenuated oral rotavirus vaccine [letter]. Lancet 1987 Nov 7; II: 1091–2
Vesikari T, Rautanen T, Varis T, et al. Rhesus Rotavirus candidate vaccine. Clinical trial in children vaccinated between 2 and 5 months of age. Am J Dis Child 1990 Mar; 144: 285–9
Hanlon P, Hanlon L, Marsh V, et al. Trial of an attenuated bovine rotavirus vaccine (RIT 4237) in Gambian infants. Lancet 1987 Jun 13; I: 1342–5
Christy C, Madore HP, Pichichero ME, et al. Field trial of rhesus rotavirus vaccine in infants. Pediatr Infect Dis J 1988; 7(9): 645–50
Green KY, Taniguchi K, Mackow ER, et al. Homotypic and heterotypic epitope-specific antibody responses in adult and rotavirus vaccinees: implications for vaccine development. J Infect Dis 1990 Apr; 161: 667–79
Glass RI, Gentsch JR, Ivanoff B. New lessons for rotavirus vaccines. Science 1996 Apr 5; 272: 46–8
Bishop RF, Barnes GL, Cipriani E, et al. Clinical immunity after neonatal rotavirus infection. A prospective longitudinal study in young children. N Engl J Med 1983 Jul 14; 309(2): 72–6
Mata L, Simhon A, Urrutia JJ, et al. Epidemiology of rotaviruses in a cohort of 45 Guatamalan Mayan Indian children observed from birth to the age of three years. J Infect Dis 1983 Sep; 148(3): 452–61
Grinstein S, Gomez JA, Bercovich JA, et al. Epidemiology of rotavirus infection and gastroenteritis in prospectively moni- tored Argentine families with young children. Am J Epidemiol 1989 Aug; 130(2): 300–8
Bernstein DI, Sander DS, Smith VE, et al. Protection from rotavirus reinfection: a 2-year prospective study. J Infect Dis 1991 Aug; 164: 277–83
Velázquez FR, Matson DO, Calva JJ, et al. Rotavirus infection in infants as protection against subsequent infections. N Engl J Med 1996 Oct 3; 335(14): 1022–8
Ward RL, Bernstein DI, ia]US Rotavirus Vaccine Efficacy Group. Protection against rotavirus disease after natural rotavirus infection. J Infect Dis 1994 Apr; 169: 900–4
Vesikari T. Rotavirus vaccines against diarrhoeal disease. Lancet 1997 Nov 22; 350: 1538–41
Midthun K, Kapikian AZ. Rotavirus vaccines: an overview. Clin Microbiol Rev 1996 Jul; 9: 423–34
Orenstein WA, Hadler S, Kuritsky JN, et al. Rotavirus vaccines — from licensure to disease reduction. J Infect Dis 1996 Sep; 174Suppl. 1: S118–24
Partriarca PA, Wright PF, John TJ. Factors affecting the immunogenicity of oral poliovirus vaccine in developing countries: review. Rev Infect Dis 1991 Sep–Oct; 13: 926–39
World Health Organization Collaborative Study Group on Oral Poliovirus Vaccine. Factors affecting the immunogenicity of oral poliovirus vaccine: a prospective evaluation in Brazil and the Gambia. J Infect Dis 1995 May; 171: 1097–105
Hermann JE, Chen SC, Fynan EF, et al. Protection against rotavirus infections by DNA vaccination. J Infect Dis 1996; 174Suppl. 1: S93–7
Martyn J, Wang L, Nagesha H, et al. Immune response to porcine rotavirus VP7 expressed as an OMP a fusion protein in the bacterial outer membrane [abstract]. Vaccines beyond 2000; 1997 M 6–9; Gold Coast, Queensland, Australia, P14
Conner ME, Zarley CD, Hu B, et al. Virus-like particles as a rotavirus subunit vaccine. J Infect Dis 1996; 174Suppl. 1: S88–92
Khoury CA, Moser CA, Speaker TJ, et al. Oral inoculation of mice with low doses of microencapsulated, noninfectious rotavirus induces virus-specific antibodies in gut-associated lymphoid tissue. J Infect Dis 1995 Sep; 172: 870–4
Lang DR, Glass RI, Compans RW. Summary of the Fifth Rotavirus Vaccine Workshop. J Infect Dis 1996 Sep; 174Suppl. 1: S3–4
Henchal LS, Midthun K, Goldenthal KL. Selected regulatory and scientific topics for candidate rotavirus vaccine develop- ment. J Infect Dis 1996 Sep; 174Suppl. 1: S112–7
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Foster, R.H., Wagstaff, A.J. Tetravalent Human-Rhesus Reassortant Rotavirus Vaccine. BioDrugs 9, 155–178 (1998). https://doi.org/10.2165/00063030-199809020-00005
Published:
Issue Date:
DOI: https://doi.org/10.2165/00063030-199809020-00005