1921
Volume 76, Issue 3
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

The feasibility of using a sensitive polymerase chain reaction (PCR) to evaluate malaria vaccines in small group sizes was tested in 102 adult Gambian volunteers who received either the malaria vaccine regimen FP9 ME-TRAP/MVA ME-TRAP or rabies vaccine. All volunteers received the antimalarial drugs primaquine and Lapdap plus artesunate to eliminate malaria parasites. Volunteers in a further group received an additional single treatment with sulfadoxine-pyrimethamine (SP) to prevent new infections. There was substantially lower T-cell immunogenicity than in previous trials with this vaccine regimen and no protection against infection in the malaria vaccine group. Using the primary endpoint of 20 parasites per mL, no difference was found in the prevalence of low-level infections in volunteers who received SP compared with those who did not, indicating that SP did not reduce the incidence of very low-density infection. However, SP markedly reduced the incidence of higher density infections. These findings support the feasibility and potential of this approach to screen pre-erythrocytic vaccines for efficacy against infection in small numbers of vaccinees in endemic areas.

Loading

Article metrics loading...

/content/journals/10.4269/ajtmh.2007.76.486
2007-03-01
2017-11-24
Loading full text...

Full text loading...

/deliver/fulltext/14761645/76/3/0760486.html?itemId=/content/journals/10.4269/ajtmh.2007.76.486&mimeType=html&fmt=ahah

References

  1. Hermsen CC, Telgt DS, Linders EH, van de Locht LA, Eling WM, Mensink EJ, Sauerwein RW, 2001. Detection of Plasmodium falciparum malaria parasites in vivo by real-time quantitative PCR. Mol Biochem Parasitol 118 : 247–251.
  2. Bejon P, Andrews L, Andersen RF, Dunachie S, Webster D, Walther M, Gilbert SC, Peto T, Hill AV, 2005. Calculation of liver-to-blood inocula, parasite growth rates, and preerythrocytic vaccine efficacy, from serial quantitative polymerase chain reaction studies of volunteers challenged with malaria sporozoites. J Infect Dis 191 : 619–626.
  3. Andrews L, Andersen RF, Webster D, Dunachie S, Walther RM, Bejon P, Hunt-Cooke A, Bergson G, Sanderson F, Hill AV, Gilbert SC, 2005. Quantitative real-time polymerase chain reaction for malaria diagnosis and its use in malaria vaccine clinical trials. Am J Trop Med Hyg 73 : 191–198.
  4. 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. 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.
  5. 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.
  6. 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.
  7. Moorthy VS, Imoukhuede EB, Milligan P, Bojang K, Keating S, Kaye P, Pinder M, Gilbert SC, Walraven G, Greenwood BM, Hill AS, 2004. A randomised, double-blind, controlled vaccine efficacy trial of DNA/MVA ME-TRAP against malaria infection in Gambian adults. PLoS Med 1 : e33.
  8. Dunachie SJ, Walther M, Epstein JE, Keating S, Barthoud T, Andrews L, Anderson RF, Bejon P, Goonetilleke N, Poulton I, Webster DP, Butcher G, Watkins K, Sinden RE, Levine GL, Richie TL, Schneider J, Kaslow D, Gilbert SC, Carucci, DJ, Hill AV, 2006. A DNA prime-modified vaccinia virus ankara boost vaccine encoding thrombospodin-related adhesion protein but not circumsporozoite protein partially protects healthy malaria-naive adults against Plasmodium falciparum sporozoite challenge. Infect Immun 74 : 5933–5942.
  9. Greenwood B, 2002. The molecular epidemiology of malaria. Trop Med Int Health 7 : 1012–1021.
  10. Mangold KA, Manson RU, Koay ES, Stephens L, Regner M, Thomson RB Jr, Peterson LR, Kaul KL, 2005. Real-time PCR for detection and identification of Plasmodium spp. J Clin Microbiol 43 : 2435–2440.
  11. Webster DP, Dunachie S, Vuola JM, Berthoud T, Keating S, Laidlaw SM, McConkey SJ, Poulton I, Andrews L, Andersen RF, Bejon P, Butcher G, Sinden R, Skinner MA, Gilbert SC, Hill AV, 2005. Enhanced T cell-mediated protection against malaria in human challenges by using the recombinant poxviruses FP9 and modified vaccinia virus Ankara. Proc Natl Acad Sci USA 102 : 4836–4841.
  12. Walther M, Thompson FM, Dunachie S, Keating S, Todryk S, Berthoud T, Andrews L, Andersen RF, Moore A, Gilbert SC, Poulton I, Dubovsky F, Tierney E, Correa S, Huntcooke A, Butcher G, Williams J, Sinden RE, Hill AV, 2006. Safety, immunogenicity, and efficacy of prime-boost immunization with recombinant poxvirus FP9 and modified vaccinia virus Ankara encoding the full-length Plasmodium falciparum circumsporozoite protein. Infect Immun 74 : 2706–2716.
  13. Walther M, Dunachie S, Keating S, Vuola JM, Berthoud T, Schmidt A, Maier C, Andrews L, Andersen RF, Gilbert S, Poulton I, Webster D, Dubovsky F, Tierney E, Sarpotdar P, Correa S, Huntcooke A, Butcher G, Williams J, Sinden RE, Thornton GB, Hill AV, 2005. Safety, immunogenicity and efficacy of a pre-erythrocytic malaria candidate vaccine, ICC-1132 formulated in Seppic ISA 720. Vaccine 23 : 857–864.
  14. Dunachie SJ, Walther M, Vuola JM, Webster DP, Keating SM, Berthoud T, Andrews L, Bejon P, Poulton I, Butcher G, Watkins K, Sinden RE, Leach A, Moris P, Tornieporth N, Schneider J, Dubovsky F, Tierney E, Williams J, Gray Heppner D Jr, Gilbert SC, Cohen J, Hill AV, 2006. A clinical trial of prime-boost immunisation with the candidate malaria vaccines RTS,S/AS02A and MVA-CS. Vaccine 24 : 2850–2859.
  15. Vuola JM, Keating S, Webster DP, Berthoud T, Dunachie S, Gilbert SC, Hill AV, 2005. Differential immunogenicity of various heterologous prime-boost vaccine regimens using DNA and viral vectors in healthy volunteers. J Immunol 174 : 449–455.
  16. Moorthy VS, Imoukhuede EB, Keating S, Pinder M, Webster D, Skinner MA, Gilbert SC, Walraven G, Hill AVS, 2004. Phase 1 evaluation of 3 highly immunogenic prime-boost regimens, including a 12-month reboosting vaccination, for malaria vaccination in Gambian men. J Infect Dis 189 : 2213–2219.
  17. Webster DP, Dunachie S, McConkey S, Poulton I, Moore AC, Walther M, Laidlaw SM, Peto T, Skinner MA, Gilbert SC, Hill AV, 2006. Safety of recombinant fowlpox strain FP9 and modified vaccinia virus Ankara vaccines against liver-stage P. falciparum malaria in non-immune volunteers. Vaccine 24 : 3026–3034.
  18. Lalvani A, Brookes R, Hambleton S, Britton WJ, Hill AV, Mc-Michael AJ, 1997. Rapid effector function in CD8+ memory T cells. J Exp Med 186 : 859–865.
  19. Pombo DJ, Lawrence G, Hirunpetcharat C, Rzepczyk C, Bryden M, Cloonan N, Anderson K, Mahakunkijcharoen Y, Martin LB, Wilson D, Elliott S, Eisen DP, Weinberg JB, Saul A, Good MF, 2002. Immunity to malaria after administration of ultra-low doses of red cells infected with Plasmodium falciparum. Lancet 360 : 610–617.
  20. Schellenberg D, Menendez C, Kahigwa E, Aponte J, Vidal J, Tanner M, Mshinda H, Alonso P, 2001. Intermittent treatment for malaria and anaemia control at time of routine vaccinations in Tanzanian infants: a randomised, placebo-controlled trial. Lancet 357 : 1471–1477.
  21. Schellenberg D, Menendez C, Aponte JJ, Kahigwa E, Tanner M, Mshinda H, Alonso P, 2005. Intermittent preventive antimalarial treatment for Tanzanian infants: follow-up to age 2 years of a randomised, placebo-controlled trial. Lancet 365 : 1481–1483.
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.2007.76.486
Loading
/content/journals/10.4269/ajtmh.2007.76.486
Loading

Data & Media loading...

  • Received : 23 Jul 2006
  • Accepted : 27 Oct 2006

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error