Malaria vaccine development: A multi-immune response approach

Letters ovalocytos~s. ~ red blood cell polymorphsm. linked to selection by malana ~n PNG (Papua New Guinea) su~e:ts that this difference in morality ~sa recent phenomenon, Ovalocytos 5 r,~sults from an a!tered band 3 protein", and g~vesprotection to heterozygotes from severe malaqa:. However. homozygotes are not feundg: ' .the lack of :! i'unctional band 3 prote~n presumably results in death at an ear;>, fetat age. in the Madang region, approx,matety 15% of the population are oval0c/t
curt'eat d,fference ,n dean ,-,ttes ,n Afl-
2 C~tt :n;.JA ~-r d (1986) A m j TroD MerJ H # 35, 3 15 3 Behzanov.Y c,~d (1997) Arm hop 63. 241 253 't Saul,A {~987} B~I Er]mmol &;s 77, 589 602 5 Craves.PM. e~ ~1 (1990/) Ab# fled 27. 134 I.i7

6 Saul.A. et d (19979Acre T,cp 63 267 273 7 jones. G L et rl/ f 1990} B ,£!1,,', 8:,1~!~sA,-~; to%. 33 40 8 Genton. B. et d (t995} N;ture -~78 564 565 9 l.,u,S,C e~ ~i;(1994) Blood 84 3590 3991

10 Esp~no.F et d (199~) Act,,' /rob 63. 221 2"~n &lla~ S a 4

i Snow. P,i'i ,lrv1i< iF,,h.K ~i 995} i',;r
T?-eQueenganu Inst,tute d Medical Rese~lrch Post Office, Royal Tnsbane ~tosplt#, Bnsban-. Qu,_'er,sl;l* t 4029. ;,ustn~l,a

B o o k Reviews Malaria ~/acc;ne Development: A Multi-Immure Respo.me Approach edited b/Stephen L Hoffrna#~,ASM Press, 1 9 9 6 , $75.00 (310/~ages) ISBN I .;5581 I!! 6 W e are celebrating this year the first centenary of Sir Rot, aid Ross' paper reporting the discovery that Pldsmocfium parasites are transmitted by mosqu;toes. A few 7ears before. Alphonse Lateran had discovered that malaria was caused by a blood protozoon. But the I~ght of humans against malana g,~u~ bad many centuries. Quinine was first brought to Europe from South Amenca in the I 7th century, and since then. stocks and monopoile,; pc..~mit;;n~, it ha~ been system:lbc,,Py used to treat 'fevers'. And several thousand yea, s back. fishing nets were beng used ~n the Ni!e Valley dS early pre,:,_lrsors of ti;,: recently rediscovered insectlcide/rcpellent impregnated mosqulto nets. The need and search for a malaria vaccine was reinforced in the 1960s by the partial, and st41 mucL debated fa,lure of the malada eradication campmgn. ] ~e first proof of pnnciple that effective immun~zatlon could be achie/ed was provided b~ huPnan volunteers ~mmun,zed with in-ar~,ated sporozoites being protected against challenoe. S~nce theq, and w~th the deve;opments in immunoiog.y, molecular bir, logy and peptlde chemistr/, t h e e has been m~,ch improvement in th2 load tO Jeveloping and deploying for public health use a c'ost-effective malaria vaccir.e. Whether the speed or development n',e.eD the expectation~ r:~is:-.'db I m,m~ rese,-rchers from ~he eal :y i970s unt,i tile pm~ont .a.~y.is a m, ~: '-c ¢oersona! judgement. But few ~,>~.!~ rJ~sagreethat ,re arc ce~alnly a lot clo[e. ~<,,achlev,ng the final aims. '~evenl different ar,t.gens, from dlherent stages in the oar.site's life cycle. havt.~ indL
different an*rnal models, A pre-elythroc/t: vaccine (RYS.S/ h.is recently shown some ewdence of inducing protection in a small number of human volunteers agmnst ~,utologous challenge in a phPtse Ila trial. And the s)nthetlc peptlde vaccine SPf66 has shov n ewdence of protectlor in a pi,tse ila heterologous challer,#:tr a! as '.*,'el: ~;s moderate, but stttlStlcally significant

protection under natural challenge ~n at least tilree r,{~dv,::zed control phase III field reals (RCTs). Induced by o, pa, a~lel to these developments, ti~e,'e is the pert., #ed f{,~lln~ that the pace ,~f malana vaccine development is qulcke,~lng, and new efforls and in,ttabves,~rcbelng envlsa$1ed and imotenlented. The recent Dal, ar

conference, the renewed ict~l ost of the VVodd Bank and W H O launching the Afii.:an Malana Initiative the m:)tdater ]~ mOagves pr omoted by the NIH, the iongte,-m support of [he European Un~on and the cet:,!y~t ~ole of TDR. co,,,;~!eH w,th some intere.* and room re: pa~ inel~_hlp with industrl ~: e all s~gnsin the iIgN d.-ectlon that cannot be overstated. The l-ook presented here ~s the,e{on_~ hmely. h e Edito~ is a we!l-respected malanolog~st. 1 leader in ,-accine de,,elopment and h,ls a broad and multldisc:phnar/appro;Kh to Vetoed+ca! research based on h,~ own t.~lckg:~un~ thg,: ~srare, .~qd g,,,es h,m a &ood grasp and knowleo!.e o f t ~aL~laa l-an~ll~ t-ore public healfl~ ~ues, eDtdeml0t0gy ind cilnlcai management tk rough to the molecula; bas~sot pathogcnes,s The book therefore addresses ai~ these !ssues, by some of the leading figuv,~s II] each field.

I d"-ert rnnsequence of such wide authorsh 9 ~sthe vanabllit/in the format, !earth ~Lmber of referem:es and style of each chapter. TPere is also a rerna:i<
B o o k Reviews further editonal assistance,but does address some of the important issues involved in fielo testing. I believe there is some consensus (probably the only one surrounding SPf66), that the development and testing of this product has highlighted the central role of field testing of a vaccine in endemic areasas part of the development process. We have now learned a lot and are aware of the problems of setting case definitions. standardizing case ascertainment methods use of placebos, and in general the desirability of ~andardizing protocols. Finally, this chapter highlights the central

role of phase lla trials. In the absence of sut~roga~emarkei-sof prote~ion or optimal animal models, and given the complexity and expense of phase III trials, phase Ila tdals (challenge experiments in a small number of volunteers) may become a major bottleneck in the fundamentally important path of screening, developing and testing of new blood-stage vaccines, combinations of different antigens or incorporation of new adjuvants. The bcsk is i.i~neiy and triteresting, ',i. highlights not only the enormous progress achieved over the past few years, but also the mayor hurdles and uncertainties that

The Immunology of Host-Ectoparasitic Arthropod Relationships edited by Stephen K. Wikel, CAB International, 1996. £60.00 (352 pages) ISBN 0 85199 125 4 The best feature of this book is that it achieves its primary goal: to present enough information about the vertebrate immune response to be of value to entomologists or insect physiologi:~tswho are intere~,:d in ho~ responses to arthropods, and enough information about arthropod salivarygland and gut physio~og'yto De useful [o the imrqunolo:~ists seeking to learn more about insects or other arthropods. Both audiences will be served by this book, - Nevertheless, several aspects of the book bothered me. For example, several chapters are by authors residing in the same department, the Department of Entomology at Oklahoma State, hence narrowing the focus. A chapter by one of the long-time leaders in this fie!d, Jose Ribeiro, would have been a welcome addition. The currency of the literature reviews vades significantly from chapter to

chapter, in several cases,the classic papers ,~ther than the latest significant citations are given. Despite these concerns, the book is nicely balanced with approximately 50% devoted to arthropod-related tot.its, and the remainder devoted to immunological topics, including the immunology of the skin. The immune response to specific components of arthropod saliva are described, as well as the counteradaptations of the arthropod involved. The book opens with a description of the major arthropod groups of medical and veterinary importance (and hence is useful to practitioners who need this type of basic information), then proceeds to describe the mouthparts and salivary glands which invoke the vertebrate immune response, This reader had no idea that the responses to fleas, mosquitoes, biting flies, ticks, scabies and mites differed

Maiaria: A Manual for Community Health Workers World Health Organization, 1996. SFI 1.20 (46 pages) ISBN 92 4 154491 0 This WHO manual gives good sound practi-:al advice to the community health worker. The manual is a col ,ven~entsize to can')' around, easy to read and use, with a nice layout that dearly emphasizes the key points with plenty of relevar,~illustrations, The manual explains the simple things that the health worker can do to promote awareness of malaria infection and the methods of preventing mosquito bites in their community. All the sections are filled with wonderful illustrations to help the health

320

worker understand how malaria infection is spread and how it is prevented, The last section gives a very comprehensive stepby-step approach to the recognition of maladainfection. The warning signs of severe malaria infection are ilighlighted with clear instructions on what the health worker should do. The importance of taking the correct dose of chloroqL,in'~;and completing the course is also emphasized (w th lots of tab es), I liked the way the manual adapt.~;to the health workers' local situation. It asks

remain ahead of us. However, like every book published on such a fast-movlng field. it risks being outdated very shortly. This would mean that we are coming a few steps closer to the aim of developing a vaccine for use in malaria control programmes that will ,'educe the huge burden of malaria morbidity and mortality worldwide, and, most urgently, in sub-Saharan Africa.

Pedro L Alonso Epidemiologyand BiostatisticsUnit Hospital Clinic Unlversidadde Barcelona.Spain

so widely and with such comFlexity. These are dealt with in separate chapters. The book's balanced presentation will ensure that the volume is likely to be purchased by many immunologists and medical/veterinary entomologists seeking to know more about the interface between the vertebrate immune response and the arthropod seeking a bloodmeal. This topic is not addressed in most medical or entomology textbooks, ancJ hence this volume is qu~te useful for both research and teaching purposes. I know I will use the information presented or, the vertebrate immune response and the current status of vaccination using salivary and gut antigens from the arthropod in a course entitled 'Biochemical Host~Parasite Relationsh!ps' and am grater'u] to find a summary of this type of information on immunological approaches to control of bloodfeeding arthropods in a single source.

Nancy E. Beckage Department of Entomok~gy Universityof California-Riverside 615A Street Davis,CA 95616 USA

them to find out how common malada is in their village, and to document what the national drug policy for first-line treatment o[ uncomplicated malaria is. The ma~,aal also explains the key role that the health worker has in assessingthe extent of the malaria problem in tneir community by keeping records and doing monthly reports In summary, years of WHO experience with malaria programmes has led to the production of a good comprehensive and 'user friendly' manual, which is a useful tool for the community health worker.

Sh~ron Welby Liv¢rpoul Schoolof TropicalMedicine PembrokePlace Liverpool UK L3 5QA

ParasitologyToday,vol. 13, no. 8, 1997