Approaches to malaria vaccine development using the retrospectroscope.
Approaches to malaria vaccine development using the retrospectroscope.
复制标题
使用回顾镜开发疟疾疫苗的方法。
DOI：
10.1128/iai.00122-09
复制
发表时间：
2009
影响因子：
3.1
通讯作者：
Williamson,KimC
中科院分区：
文献类型：
--
作者：
Sardá,Vanessa;Kaslow,DavidC;Williamson,KimC
Seventy-five years ago, J. Gordon Thomson addressed the Royal Society of Tropical Medicine and Hygiene on the topic of immunity in malaria (102). In introducing the subject, he made several points.(i)“The literature bearing on this one aspect (immunity in malaria) of the disease in man and other animals is considerable and, therefore, it may be useful to review it and attempt to analyze critically the epidemiological, clinical, experimental and pathological evidences of immunity.”(ii)“The study of malaria by competent workers in many parts of the world has directly and indirectly supplied a mass of facts which materially assist the immunologist to make useful observations and suggest further studies.”(iii)“The knowledge already accumulated leads one to conclude that the problems of immunity in protozoal diseases are probably related closely to those already extensively investigated by bacteriologists.”(iv)“Within recent years more accurate knowledge of immunity in malaria has gradually been acquired; but it is necessary to stress the fact that there are many unsolved problems of great importance. It is not too much to state that if the mechanism of immunity in malaria were entirely solved the control of the disease and its treatment would be nearer accomplishment.” Fifty years later, 25 years ago, the first gene encoding a malaria vaccine immunogen, the circumsporozoite protein (CSP), was molecularly cloned and sequenced (29, 40). This was followed closely by the molecular cloning of the first asexual erythrocytic-stage vaccine immunogen, merozoite surface protein 1 (MSP1)(49, 74). These two antigens still remain the focus of current vaccine efforts. In the intervening years, dozens of individual genes, and ultimately the complete genome, have been sequenced (43). Concurrent with elucidation of the complete primary genomic structure of Plasmodium falciparum, the development of transfection techniques allowed direct functional analysis of specific genes (28, 110, 111). Several genes encoding vaccine targets appear to be essential for stage-specific growth, whereas other genes appear to be nonessential, which has led some investigators to conclude that these latter targets may not be ideal vaccine candidates. Significant advances have also been made in describing the cellular immune responses induced during rodent malaria parasite infections (20, 59). This work has generated an additional “mass of facts” that now need to be reconciled with the immune responses of humans, including those so well described by Thomson and colleagues. Despite this immense progress, few, if any, competent workers who study human malaria would state that the mechanism of protective immunity is entirely solved or the complete control of the disease by active immunization is likely to be a near-term accomplishment.When contemplating vaccine development for a specific pathogen, two approaches are often considered. One approach, referred to hereafter as semiempirical, is to incorporate, into a well-tolerated regimen, repeated exposures to presumed protective immunogens, the goal of which is to recapitulate naturally acquired clinical resilience, subclinical susceptibility, or ultimately clinical insusceptibility that was empirically described more than a century ago. Examples of semiempirical approaches include the whole killed virus vaccine for hepatitis A and the subunit-based vaccine for hepatitis B virus. An orthogonal approach, referred to hereafter as noetic (derived from the Greek noetikos, understanding or rational), has the goal of inducing protective immune responses that may not occur either qualitatively or quantitatively during natural infection. The …
