1921
Volume 75, Issue 1
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

We conducted a phase 1 trial of candidate malaria vaccine RTS,S/AS02A in western Kenya to determine its safety and immunogenicity in healthy adults in an area hyperendemic for malaria. Twenty adults were enrolled and received RTS,S/AS02A (50 μg of RTS,S in 0.5 mL of AS02A) by intramuscular injection on a 0-, 28-, and 178-day schedule. All 60 scheduled immunizations were given, and 18 of 20 volunteers completed the last study visit on day 210. The vaccine was safe and well-tolerated. There were no vaccine-related severe adverse events. The most common solicited adverse events associated with immunization were injection site pain and headache. The geometric mean concentration of antibodies to circumsporozoite protein was 1.9 μg/mL at baseline and it increased 2–4 weeks after each dose to 16, 17.8, and 36.6 μg/mL, respectively. These safety and immunogenicity data from adults in hyperendemic Kenya are comparable to data reported earlier from two trials in west African adults in hypo-endemic and meso-endemic areas of The Gambia. We conclude that in this small study, RTS,S/AS02A is safe and similarly immunogenic in malaria-exposed African adults of different ethnicity in different transmission settings.

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2006-07-01
2017-09-20
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References

  1. Breman JG, 2001. The ears of the hippopotamus: manifestations, determinants, and estimates of the malaria burden. Am J Trop Med Hyg 64 (Suppl): 1–11.
  2. Snow RW, Guerra CA, Noor AM, Myint HY, Hay SI, 2005. The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature 434 : 214–217.
  3. Sachs J, Malaney P, 2002. The economic and social burden of malaria. Nature 415 : 680–685.
  4. Gordon DM, McGovern TW, Krzych U, Cohen JD, Schneider I, LaChance R, Heppner DG, Yuan G, Hollingdale M, Slaoui M, Hauser P, Voet P, Sadoff JC, Ballou WR, 1995. Safety, immunogenicity, and efficacy of a recombinantly produced Plasmodium falciparum circumsporozoite protein-hepatitis B surface antigen subunit vaccine. J Infect Dis 171 : 1576–1585.
  5. Garcon N, Heppner DG, Cohen J, 2003. Development of RTS,S/ AS02: a purified subunit-based malaria vaccine candidate formulated with a novel adjuvant. Expert Rev Vaccines 2 : 231–238.
  6. Stoute JA, Slaoui M, Heppner DG, Momin P, Kester KE, Desmons P, Wellde BT, Garcon N, Krzych U, Marchand M, Ballou WR, Cohen JD for the RTS,S Malaria Vaccine Evaluation Group, 1997. A preliminary evaluation of a recombinant circumsporozoite protein vaccine against Plasmodium falciparum malaria. N Engl J Med 336 : 86–91.
  7. Kester KE, McKinney DA, Tornieporth N, Ockenhouse CF, Heppner DG, Hall T, Krzych U, Delchambre M, Voss G, Dowler MG, Palensky J, Wittes J, Cohen J, Ballou WR for the RTS,S Malaria Vaccine Evaluation Group, 2001. Efficacy of recombinant circumsporozoite protein vaccine regimens against experimental Plasmodium falciparum malaria. J Infect Dis 183 : 640–647.
  8. Heppner DG Jr, Kester KE, Ockenhouse CF, Tornieporth N, Ofori O, Lyon JA, Stewart VA, Dubois P, Lanar DE, Krzych U, Moris P, Angov E, Cummings JF, Leach A, Hall BT, Dutta S, Schwenk R, Hillier C, Barbosa A, Ware LA, Nair L, Darko CA, Withers MR, Ogutu B, Polhemus ME, Fukuda M, Pichyangkul S, Gettyacamin M, Diggs C, Soisson L, Milman J, Dubois MC, Garcon N, Tucker K, Wittes J, Plowe CV, Thera MA, Duombo OK, Pau MG, Goudsmit J, Ballou WR, Cohen J, 2005. Towards an RTS,S-based, multi-stage, multi-antigen vaccine against falciparum malaria: progress at the Walter Reed Army Institute of Research. Vaccine 23 : 2243–2250.
  9. Doherty JF, Pinder M, Tornieporth N, Carton C, Vigneron L, Milligan P, Ballou WR, Holland CA, Kester KE, Voss G, Momin P, Greenwood BM, McAdam KP, Cohen J, 1999. A phase I safety and immunogenicity trial with the candidate malaria vaccine RTS,S/SBAS2 in semi-immune adults in The Gambia. Am J Trop Med Hyg 61 : 865–868.
  10. Bojang KA, Milligan PJ, Pinder M, Vigneron L, Alloueche A, Kester KE, Ballou WR, Conway DJ, Reece WH, Gothard P, Yamuah L, Delchambre M, Voss G, Greenwood BM, Hill A, McAdam KP, Tornieporth N, Cohen JD, Doherty T, 2001. RTS,S Malaria Vaccine Trial Team. Efficacy of RTS,S/AS02 malaria vaccine against Plasmodium falciparum infection in semi-immune adult men in The Gambia: a randomised trial. Lancet 358 : 1927–1934.
  11. Alonso PL, Sacarlal J, Aponte JJ, Leach A, Macete E, Milman J, Mandomando I, Spiessens B, Guinovart C, Espasa M, Bassat Q, Aide P, Ofori-Anyinam O, Navia MM, Corachan S, Ceuppens M, Dubois MC, Demoitie MA, Dubovsky F, Menendez C, Tornieporth N, Ballou WR, Thompson R, Cohen J, 2004. Efficacy of the RTS,S/AS02A vaccine against Plasmodium falciparum infection and disease in young African children: randomised controlled trial. Lancet 364 : 1411–1420.
  12. Alonso PL, Sacarlal J, Aponte JJ, Leach A, Macete E, Aide P, Sigauque B, Milman J, Mandomando I, Bassat Q, Guinovart C, Espasa M, Corachan S, Lievens M, Navia MM, Dubois MC, Menendez C, Dubovsky F, Cohen J, Thompson R, Ballou WR, 2005. Duration of protection with RTS,S/AS02A malaria vaccine in prevention of Plasmodium falciparum disease in Mozambican children: single-blind extended follow-up of a randomised controlled trial. Lancet 366 : 2012–2018.
  13. Beier JC, Oster CN, Onyango FK, Bales JD, Sherwood JA, Perkins PV, Chumo DK, Koech DV, Whitmire RE, Roberts CR, Diggs CL, Hoffman SL, 1994. Plasmodium falciparum incidence relative to entomologic inoculation rates at a site proposed for testing malaria vaccines in western Kenya. Am J Trop Med Hyg 50 : 529–536.
  14. Bojang KA, Olodude F, Pinder M, Ofori-Anyinam O, Vigneron L, Fitzpatrick S, Njie F, Kassanga A, Leach A, Milman J, Rabinovich R, McAdam KP, Kester KE, Heppner DG, Cohen JD, Tornieporth N, Milligan PJ, 2005. Safety and immunogenicity of RTS,S/AS02A candidate malaria vaccine in Gambian children. Vaccine 23 : 4148–4157.
  15. Centers for Disease Control and Prevention, 1999. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 48 : 1–37.
  16. Centers for Disease Control and Prevention, 1991. Hepatitis B Virus: a comprehensive strategy for eliminating transmission in the United States through universal childhood vaccination: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 40 : 1–19.
  17. Mills KHG, 2004. Regulatory T cells: friend or foe in immunity to infection? Nat Rev Immunol 4 : 841–845.
  18. Ghosh K, Wu W, Antoine AD, Bottazzi ME, Valenzuela JG, Hotez PJ, Mendez S, 2006. The impact of concurrent and treated Ancylostoma ceylanicum hookworm infections on the immunogenicity of a recombinant hookworm vaccine in hamsters. J Infect Dis 193 : 155–162.
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  • Received : 26 Jan 2006
  • Accepted : 25 Feb 2006

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