Impact of a Plasmodium falciparum AMA1 Vaccine on Antibody Responses in Adult Malians

被引：52

作者：

Dicko, Alassane ^{[2
,3
]}

Diemert, David J. ^{[1
]}

Sagara, Issaka ^{[2
,3
]}

Sogoba, Moussa ^{[2
,3
]}

Niambele, Mohamed B. ^{[2
,3
]}

Assadou, Mahamadoun H. ^{[2
,3
]}

Guindo, Ousmane ^{[2
,3
]}

Kamate, Beh ^{[2
,3
]}

Baby, Mounirou ^{[2
,3
]}

Sissoko, Mady ^{[2
,3
]}

Malkin, Elissa M. ^{[1
]}

Fay, Michael P. ^{[4
]}

Thera, Mahamadou A. ^{[2
,3
]}

Miura, Kazutoyo ^{[1
]}

Dolo, Amagana ^{[2
,3
]}

Diallo, Dapa A. ^{[2
,3
]}

Mullen, Gregory E. ^{[1
]}

Long, Carole A. ^{[1
]}

Saul, Allan ^{[1
]}

Doumbo, Ogobara ^{[2
,3
]}

Miller, Louis H. ^{[1
]}

机构：

[1] NIAID, Malaria Vaccine Dev Branch, NIH, Bethesda, MD 20892 USA

[2] Univ Bamako, Dept Hematol, Malaria Res & Training Ctr, Bamako, Mali

[3] Univ Bamako, Dept Parasitol, Malaria Res & Training Ctr, Bamako, Mali

[4] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA

来源：

PLOS ONE | 2007年 / 2卷 / 10期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1371/journal.pone.0001045

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 [理学]; 0710 [生物学]; 09 [农学];

摘要：

Background. Apical Membrane Antigen 1 (AMA1) of Plasmodium falciparum merozoites is a leading blood-stage malaria vaccine candidate. Protection of Aotus monkeys after vaccination with AMA1 correlates with antibody responses. Study Design/Results. A randomized, controlled, double-blind phase 1 clinical trial was conducted in 54 healthy Malian adults living in an area of intense seasonal malaria transmission to assess the safety and immunogenicity of the AMA1-C1 malaria vaccine. AMA1-C1 contains an equal mixture of yeast-expressed recombinant proteins based on sequences from the FVO and 3D7 clones of P. falciparum, adsorbed on Alhydrogel. The control vaccine was the hepatitis B vaccine (Recombivax). Participants were enrolled into 1 of 3 dose cohorts (n = 18 per cohort) and randomized 2: 1 to receive either AMA1-C1 or Recombivax. Participants in the first, second, and third cohorts randomized to receive AMA1-C1 were vaccinated with 5, 20 and 80 mg of AMA1-C1, respectively. Vaccinations were administered on days 0, 28, and 360, and participants were followed until 6 months after the final vaccination. AMA1-C1 was well tolerated; no vaccine-related severe or serious adverse events were observed. AMA1 antibody responses to the 80 mg dose increased rapidly from baseline levels by days 14 and 28 after the first vaccination and continued to increase after the second vaccination. After a peak 14 days following the second vaccination, antibody levels decreased to baseline levels one year later at the time of the third vaccination that induced little or no increase in antibody levels. Conclusions. Although the AMA1-C1 vaccine candidate was well-tolerated and induced antibody responses to both vaccine and non-vaccine alleles, the antibody response after a third dose given at one year was lower than the response to the initial vaccinations. Additionally, post-vaccination increases in anti-AMA1 antibody levels were not associated with significant changes in in vitro growth inhibition of P. falciparum. Trial Registration. Clinicaltrials.gov NCT00343005

引用

页数：10

共 28 条

[1]

Efficacy of the RTS,S/AS02A vaccine against Plasmodium falciparum infection and disease in young African children:: randomised controlled trial [J].