of 333 children who had been successfully immunized close contact with measles patients. 1 million), Zhejiang Province, a closed area in

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1 Durtion of immunity following immuniztion with live mesles vccine: 15 yers of observtion in Zhejing Province, Chin Di Bin,1 Chen Zhihui,2 Liu Qichng,3 Wu Ting,4 Guo Chengyin,4 Wng Xingzi,5 Fng Hnhu,1 & Xing Yongzhong4 The durtion of immunity following mesles vccintion of 2882 immunized children hs been investigted in closed region of Chin for 15 yers. A totl of 12 of the children were treted s primry immuniztion subjects, nd 1547 s reimmuniztion subjects. These two cohorts were not in contct with known wild mesles virus over the whole observtion period, nd the results obtined probbly reflected the ntibody responses to mesles vccine lone. The remining 333 vccinees cme into contct with wild mesles virus, nd this permitted evlution of the protective effect of the mesles vccines tested: 4 children experienced very mild clinicl mesles, nd 329 experienced subclinicl infection, including 12 who hd hd undetectble hemgglutintion-inhibition ntibodies for 9-1 yers. These results indicte tht the immunity induced by successful primry immuniztion my persist for t lest 15 yers. Within this period, second dose of vccine only induces low ntibody responses which decrese rpidly to their originl levels. This provides strong evidence tht the immunity produced by primry immuniztion is long-lsting. However, there were some indictions tht reimmuniztion might produce better effects if live ttenuted mesles virus were used with longer intervl between doses. Mesles used to be very severe disese before the vilbility of mesles vccine. In Chin lrge outbreks occurred nnully in cities nd every 2-3 yers in rurl res. Almost every child contrcted mesles erly in life. Morbidity from mesles hs decresed drmticlly in Chin since the introduction of the vccine in 1965; however, despite this encourging trend, nd consistent with other countries' experience, n incresed incidence mong schoolchildren nd dolescents hs occurred, mny of whom hve been immunized. It is therefore importnt to determine the durtion of immunity fter primry immuniztion nd whether reimmuniztion is necessry to mintin immunity. Both these concerns hve been the subject of the present study over the period Eight ppers hve previously been published covering erlier stges of the study (1-8). Here, we report the level of ' Ntionl Institute for the Control of Phrmceuticl nd Biologicl Products, Temple of Heven, Beijing 15, Chin. Requests for reprints should be sent to Dr Di Bin t this ddress. 2 Shnghi Institute of Biologicl Products, Shnghi, Chin. 3 Chngchun Institute of Biologicl Products, Chngchun, Chin. 4 Snitry nd Anti-epidemic Sttion, Zhejing Province, Chin. 5 Zhejing Medicl University, Hngzhou, Chin. Reprint No immunity yers fter initil immuniztion, evlute the effect of reimmunizing 1547 children, nd nlyse the results of n epidemiologicl study of 333 children who hd been successfully immunized nd followed up for 12 yers before coming into close contct with mesles ptients. Mterils nd methods Study re The study ws crried out in Zhuji County (popultion: 1 million), Zhejing Province, closed re in the south of Chin. To chieve high level of immunity, bout 3 children under the ge of, 15 yers were immunized with one dose of live ttenuted mesles vccine (two strins) over 1-month period in 1973, regrdless of their pst immuniztion history. Both the immuniztion rte nd the rte of seroconversion for these children were greter thn 95%. Subsequently, ll children ged 8 months were dministered mesles vccine in n effort to protect the closed region from infection with nturl mesles virus. Becuse mesles my be subclinicl nd unrecognized, nd becuse there ws lwys the possibility tht the virus ws being imported from infected res of Chin by vriety of ge groups, it ws impossible to verify tht mesles virus ws bsent from the entire study re. Bulletin of the World Helth Orgniztion, 69(4): (1991) World Helth Orgniztion

2 Di Bin et l. However, the steps tht were tken to prevent the spred of mesles seem to hve been highly successful. An effective surveillnce nd control network ws estblished, nd it ws lid down tht every suspected cse of mesles should be notified within 2 dys nd tht clinicl investigtions of these cses, including collection of blood smples, should be crried out within 24 hours of notifiction. All reported cses of mesles in the county were investigted serologiclly. In this wy, mesles morbidity in Zhuji County ws kept successfully t very low level (verge morbidity, : 1.3 per 1). Study subjects A totl of 3233 children who hd neither been infected with mesles nor immunized ginst it before the investigtion begn in 1973 formed the study subjects in the bse re. After primry immuniztion, the sero-sttus of the children ws determined using hemgglutintion-inhibition (HI) tests. In the 15th yer of the progrmme, 2882 children were still under observtion nd ll of them hd undergone serologicl testing. These children could be divided into the following groups. * Group 1-12 children who hd not received second dose of vccine in 15 yers-the primry immuniztion subjects. * Group children who hd received second dose of vccine-the reimmuniztion subjects. * Group 3-consisting of 333 children who hd been infected (4 with clinicl nd 329 with subclinicl infection) during the whole period from , minly in 1985 when mesles outbreks occurred in the bse re. There were 122 cses of mesles in the bse re (118 nonimmunized persons, while 4 hd been immunized). A totl of 329 individuls (122 primry nd 27 reimmuniztion subjects) hd close contct with cse of mesles. 416 Vccine For primry immuniztion, the following live ttenuted (virus titre log/. 1 ml) mesles vccines were used: two domestic (Hul9l nd Chng47) nd two foreign strins (Schwrz (USA) nd Leningrd-16 (L-16) (USSR)). Limited use ws mde lso of the Hng-M13 strin, which hd better immunogenicity but high fever rte (16.1%). For reimmuniztion, two other vccines were used: formlinkilled Hu19l mesles vccine, nd primry ttenuted mesles vccine- mesles virus dpted through four pssges in chick embryo tissue culture. All the vccines were prepred in chick embryo tissue culture except the L-16, which ws cultured in guine-pig kidney cells. Routes of dministrtion For primry immuniztion, the vccine ws dministered subcutneously or by erosol, while for reimmuniztion it ws dministered subcutneously, intrdermlly, or by erosol. Serologicl tests HI tests were used to test for ntibody in ll smples of serum (bout 3 ech yer for 15 yers). The ser were first inctivted t 56 C for 3 minutes nd then llowed to bsorb unspecific gglutinins from monkey red blood cells. Serum diluted twofold from 1: 2 ws regrded s negtive. Some smples were screened using neutrliztion (NT) nd hemolysis-inhibition (HLI) tests (2, 16). Observtion period The 15-yer observtion period cn be divided into the two prts shown below. * During this time, the min ctivity ws the continued nd systemtic observtion of serologicl dynmics. * Over this 5-yer period, the study of serologicl dynmics ws continued nd n epidemiologicl study of the immunity of children ws crried out. An outbrek of 122 cses of mesles occurred in the bse re in A totl of 333 children who hd close contct with the cses were lso infected. Results Durtion of immunity fter primry immuniztion Children in Chin re routinely injected subcutneously with.2 ml of mesles vccine. However, some children receive the vccine s n erosol, dispensed using JM-2 erosol gun. Blood smples were tken from the study children every Mrch for the 15 yers of the investigtion. The HI ntibody titre declined mrkedly in the first yer, continued to decrese grdully from the second to the fourth yer, nd therefter remined stedy t low level (Fig. 1). Undetected ntibody levels were recorded in slowly incresing numbers, even mong children who hd been infected nturlly. In the closed re, four ptients lost detectble HI ntibody within 15 yers. The pttern of the HI ntibody decy ws similr mong different groups (Tble 1).

3 Durtion of immunity produced by live mesles vccine in Chin Fig. 1. Plots showing the durtion of immunity up to 15 yers fter immuniztion with Hu19, mesles vccine (SC = subcutneous; Hi Ab = hemgglutintion-inhibition ntibody) CD 1 ^ 9-4 I 8- co ED 7- E _ 6- E5i N,, ~~~~~~~~~Hu,,,1 (SC) Hu,,,1 (erosol) -- - Infection month <3 Yers - Observtion period Durtion of immunity provided by the domestic versus the imported vccines A totl of 449 children ged 8-16 months were given single.5 ml dose of one of the domestic or imported vccines. Since the routine dose of mesles vccine used in Chin is.2 ml, we compred the effects of the two doses for the Chng47 nd L-16 vccines. In order to investigte the effect of immuniztion ge on the durtion of immunity, we compred the rte of conversion to seronegtive over 14-yer period mong children whose ge t primry immuniztion ws 8-12 months or months. At the end of the 14-yer period, the following were the rtes for conversion to seronegtive: 12.8% nd 8.1% (Hul91), U =.87; 11.1% nd 1.2% (Chng47), U =.14; 15.4% nd 9.7% (Schwrz), U =.85; 12.7% nd 2% (L-16), U = 1.7. No significnt differences between the vccines were found (P>.5). It cn therefore be concluded tht the durtion of immunity produced by the Hul9l nd Chng47 vccines is similr to tht of the Schwrz vccine, nd is better thn tht induced by the L-16 vccine under these circumstnces (Tble 2). The results shown in Tble 3 indicte tht the durtion of immunity induced in children who received.5 ml dose of Chng47 or L-16 strins ws better thn tht induced by.2 ml dose, lthough the differences were not sttisticlly significnt. Durtion of immunity following reimmuniztion t vrious intervls A totl of 1547 subjects were involved in this spect of the study, ll of whom hd undergone successful primry immuniztion s confirmed serologiclly in Three groups were immunized t different intervls between primry nd secondry injection s outlined below. * Group A: 42 children whose HI ntibody titre decresed 2-3 yers fter primry immuniztion by c 1: 16. Group B (519 children) nd group C (68 children) were reimmunized fter 5-7 yers nd 1-11 yers, respectively. The results in Tble 4 show tht the increse in HI ntibody titre fter reimmuniztion ws low, regrdless of the intervl between doses nd the ntibody level before the booster dose ws given. However, for children with the sme HI ntibody titre before reimmuniztion the proportion who becme seronegtive ws mrkedly dependent on the intervl between doses. For exmple, the HI ntibody titres of children in group A were more likely to become seronegtive, especilly those with HI ntibody titres < 1: 2. The incresed ntibody Tble 1: Antibody levels nd negtive conversion rtes mong the children following primry immuniztion with mesles vccine (.2 ml) or nturl infection with mesles virus over the 15 yer study period Hi Ab GMT Mesles vccine Route children 1 month 1 yer 3 yers 5 yers 7 yers 9 yers 11 yers 13 yers 15 yers Hu,91 SC,, Aerosol Chng47 Aerosol Hng-M,3 SC Nturl infection 27 NTc b c Hemgglutintion-inhibition ntibody geometric men titre. SC = subcutneous injection. NT = not tested. 417

4 Di Bin et l. Tble 2: Comprison of the durtion of immunity produced by primry immuniztion with.5 ml of mesles vccine over 14-yer follow-up period Age t vccintion Hi Ab GMT" Vccine (months) children (1 month) 2 yers 4 yers 6 yers 8 yers 1 yers 12 yers 14 yers Hu,,, Chng Schwrz L Hemgglutintion-inhibition ntibody geometric men titre. Tble 3: Comprison of the durtion of immunity produced by primry immuniztion with different doses of the Chng47 or L-16 mesles vccine over 14-yer follow-up period Dose HI Ab GMTb Vccine (ml)' children (1 month) 2 yers 4 yers 6 yers 8 yers 1 yers 12 yers 14 yers Chng L The following doses were used: Chng47: 3.5logTCID5 per.1 ml; L-16: 3.25logTCID5 per.1 ml. b Hemgglutintion-inhibition ntibody geometric men titre. levels dropped to pproximtely their originl levels within 1-2 yers. Although the ntibody titres 3 weeks fter reimmuniztion of ll subjects in the three groups were very low, the HI levels for groups B nd C were less vrible thn those for group A. Children in group A exhibited poor immune responses both fter primry immuniztion nd reimmuniztion. Also, the increse in ntibody titre cused by reimmuniztion does not pper to produce lsting immunity. The effects of reimmuniztion therefore pper to be simply n nmnestic rection to booster dose. Durtion of immunity ccording to vccines nd dministrtion route A totl of 519 children in group B were reimmunized s follows: 344 children were injected with the live ttenuted vccine by subcutneous, intrcutneous, or erosol routes; 127 received the killed vccine (subcutneously); nd 48 primry ttenuted vccine (subcutneously). The results in Tble 5 show tht 3 weeks fter reimmuniztion the geometric men HI ntibody titres were similr nd low. Also, there were no significnt differences between the titres 8 yers 418 fter reimmuniztion or between the rtes of those becoming seronegtive. Durtion of immunity: primry immuniztion versus reimmuniztion One wy to determine whether reimmuniztion cn produce high levels of immunity is to compre the durtion of immunity mong children who hve similr history of immuniztion. A totl of 755 children hd HI ntibody titres s 1: 16 t 2-3 yers fter primry immuniztion. Of these, 42 children received second dose of vccine, while the remining 335 received only the first dose. The rtes of conversion to seronegtive for these two groups of children 4, 8 nd 12 yers fter reimmuniztion (Tble 6) indicte tht the durtion of immunity for children who received second dose ws no longer thn for those receiving one dose. Durtion of immunity following successful or unsuccessful reimmuniztion The ntibody levels produced by successful reimmuniztion were compred with those produced by unsuccessful immuniztion.

5 Durtion of immunity produced by live mesles vccine in Chin Tble 4: Comprison of the durtion of immunity following reimmuniztion t different intervls Hi Ab GMT8 Reimmuniztion Before 3 weeks fter Group intervl (yers) children revccintion reimmuniztion 1 yer 4 yers 8 yers A B < C NTb A B C NT A B C NT A B C NT A B C NT b Hemgglutintion-inhibition ntibody geometric men titre. NT = not tested. Tble 5: Results obtined following revccintion with different mesles vccines nd routes of dministrtion HI Ab GMT" HI Ab GMT fter:b 3 weeks fter Vccine Route" children reimmuniztion 2 yers 4 yers 6 yers 8 yers SC (.9)C 7.6 (3.8) 7.4 (3.8) Live (Hu,g,) IC (1.5) 7.7 (1.5) Aerosol (1.5) 7.2 (1.5) Killed SC (.8) 7.2 (.8) Primry SC ttenuted Sc = subcutneous; IC = intrcutneous. b Hi Ab GMT = hemgglutintion-inhibition ntibody geometric men titre. c Figures in prentheses re the % who becme seronegtive. Tble 7 shows tht the rtes of conversion to seronegtive for the successful vccinees 4, 8 nd 12 yers fter reimmuniztion were unexpectedly slightly higher thn those for whom reimmuniztion ws unsuccessful. This perhps rose becuse before reimmuniztion, successful vccinees hd lower ntibody titres thn those who were unsuccessful. Durtion of immunity following nturl infection nd reimmuniztion Wild mesles virus cn stimulte n increse in ntibody titres both fter infection or immuniztion. It might be sked whether there is ny difference between the booster effect produced by the wild virus nd tht stimulted by mesles vccine, nd whether ptients who re cliniclly infected experience greter immune response thn tht induced in ptients with subclinicl infections. During the 1985 epidemic, blood smples were collected from 53 children 1 month fter infection with wild mesles virus Ṫhe results obtined (Tble 8) indicte tht the four cses of clinicl mesles hd high ntibody responses 1 month fter infection nd greter durtion of immunity for 1-3 yers fterwrds, even though 4-8 yers before infection their HI ntibody titres were ll < 1: 2. This contrsts with the sitution following reimmuniztion. For subcliniclly infected children the ntibody response nd durtion of immunity were intermedite between those cused by clinicl infection nd reimmuniztion (Fig. 2). Becuse it is simple nd specific nd cn be used to screen the ntibody titres for lrge-scle field trils, the HI ntibody test is widely used ll over the 419

6 Di Bin et l. Tble 6: Comprison of the durtion of immunity of children following primry nd secondry immuniztion with mesles vccine t the sme Hi ntibody titre HI Ab GMT" 2-3 yers fter primry immuniztion Dose children 1 yer 4 yers 8 yers 12 yers < 2 Primry Secondry Primry Secondry Primry Secondry Primry Secondry Primry Secondry Hemgglutintion-inhibition ntibody geometric men titre. Tble 7: Comprison of the durtion of immunity following successful or unsuccessful reimmuniztion with mesles vccine Successful immuniztion Unsuccessful immuniztion Yers fter negtive negtive negtive reimmuniztion children conversions n conversions n conversions (39.9) (29.2) (2.4) (1.7) (2.) 25 3 (1.2) Figures in prentheses re percentges. Tble 8: Comprison of the durtion of immunity induced by nturl infection with mesles virus or by reimmuniztion mong the study children Hi Ab GMT children Slb S2C 1 yer 2 yers 3 yers Infecti Clinicl 4 <2 (1.)d Infection lsubclinicl (24.5) Reimmuniztion (.8) (.2) 7.6 (1.2) 7.7 (1.2) Hemgglutintion-inhibition ntibody geometric men titre. b Ser tken before infection or reimmuniztion. c Ser tken 1 month fter infection or reimmuniztion. d Figures in prentheses re the negtive conversion rte (%). world to detect immunity to mesles. The test is, however, not very sensitive; it therefore does not imply tht n individul whose HI ntibody titre is undetectble (< 1: 2) is not immune. In the present study 333 children hd been exposed to wild mesles virus nd becme infected. Of these, 78 with n HI ntibody titre < 1: 2 hd close contct with mesles cses, but only four subjects exhibited clinicl infection; the remining 74 children experienced subclinicl infections, nd no clinicl symptoms were observed fter creful medicl exmintion. The results in Tble 9 show tht 4-8 yers fter immuniztion the HI ntibody titres for the four clinicl cses were < 1: 2, while 12 children hd lost their HI ntibody titre fter 9-1 yers but still hd immunity to wild mesles virus. Discussion In Chin the sme live ttenuted mesles vccine nd the recommended ge for immuniztion hve been used since 1965, nd the Hul91 nd Chng47 vccines hve been widely used from the very beginning. From 1965 to 1984 mjor concern ws vccine filure cused by use of the het-lbile liquid products. The occurrence of mesles cses mong 42

7 Durtion of immunity produced by live mesles vccine in Chin Fig. 2. Comprison of geometric men hemgglutintioninhibition ntibody (HI Ab) titre between infection nd reimmuniztion t, Clinicl 1 month 1 yer Observtion period mesles SubclinIcl mesles Reimmunizlon - * f 2yers 3 yers previously immunized children rose becuse either the protection produced by the vccine ws of short durtion or seroconversion did not occur fter immuniztion, often becuse impotent vccine ws used. Clinicl disese did occur in some children who hd previously received mesles vccine, but ntibodies were detected in few of them fter primry immuniztion or before the development of clinicl disese. It is therefore difficult to determine whether wning immunity or filure to seroconvert fter immuniztion ws the rel cuse of mesles mong children who hd been immunized. Reimmuniztion my overcome the problems of filure to seroconvert. Since lyophilized vccine completely replced liquid mesles vccines in 1985 in Chin, nd the cold chin hs been progressively improved, dministrtion of impotent vccine hs become less of problem. The durtion of immunity induced by mesles vccine ws investigted in the study not only by using the results of serologicl tests nd the persistence of immunity following primry nd second immuniztions in closed geogrphicl region, but lso by epidemiologicl study of 333 vccinees who hd been infected with wild mesles virus. While it is possible tht no wild mesles virus entered the study popultion during the 15 yers of the study period, it must be ccepted relisticlly tht t lest some of the study popultion contrcted the wild virus infection. Circumstntil evidence suggests this number ws not high, nd presumbly does not lter the vlidity of the overll conclusions significntly. In norml field sitution, it would be resonble to expect tht ny circulting wild virus ws producing nturl boosting effect on primry immuniztion. In such circumstnces, the durtion of immunity could be expected to be even longer thn the 15 yers studied in this tril. Our observtions wrrnt the conclusions outlined below. * About 85% of the vccinees still hd detectble HI ntibody titres 15 yers fter primry immuniztion. However, even when the HI titres decresed to undetectble levels this did not imply tht they hd lost immunity to wild mesles virus. A totl of 82% of the children who hd no mesurble HI ntibody 1-5 yers lter, still hd detectble levels of neutrlizing ntibody (9). Epidemiologicl investigtions corroborted this evidence, since of 78 children with undetectble HI ntibody titres 1-1 yers lter who hd close contct with mesles ptients only four (HI ntibody titre < 1: 2 for 4-8 yers) experienced mild clinicl mesles. The remining 74 children suffered only subclinicl infections, even the 12 children who hd hd undetectble HI ntibody levels for 9-1 yers. * There hve been severl reports bout the durtion of immunity provided by mesles vccine (1-13). One of these studies consisted only of n ssessment of n epidemic without ny systemtic serologicl confirmtion of the findings (11); nother ws restricted to n investigtion of wild mesles virus (12); nd third ws crried out in n open community (13). In contrst, in our study ll 12 primry vccinees lived in the closed region nd hd nnul serologicl tests. * In the context of our study, reimmuniztion ws Tble 9: Correltion between hemgglutintion-inhibition ntibody titres nd mesles infection mong children exposed to wild mesles virus in the study No. with HI Ab8 titres < 1: 2 for: Type of infection children 1-2 yers 3-4 yers 5-6 yers 7-8 yers 9-1 yers Clinicl Subclinicl Hemgglutintion-inhibition ntibody. 421

8 Dl Bin et l. tken to be the dministrtion of second dose to subjects who hd hd serologiclly confirmed response to primry mesles immuniztion. This definition differs from tht used by Linnemnn et l. (14) nd Blck et l. (15), inter li, who defined reimmuniztion s second dose given to children who, for vrious resons, were immuniztion filures. * In the present study, reimmuniztion using different vccines, routes, nd intervls (see Tble 5) unexpectedly produced very similr ntibody response profiles, i.e., 3 weeks fter the booster dose the HI ntibody titres were much lower nd decresed rpidly compred with the HI ntibody titres fter primry inocultion. The HLI ntibody did not increse s much s the HI ntibody in those who were successfully reimmunized (16). The second dose of mesles vccine therefore does not pper to produce lsting ugmenttion of immunity, even with 1-11-yer intervl between the primry nd second doses, nd with subjects who exhibited undetectble HI ntibody titres over mny yers. Other workers hve reported similr results (17-19). For exmple, Krugmnn found tht reimmuniztion of seven children who hd been observed for 14 yers fter primry immuniztion boosted their HI ntibody titre from < 1: 2 to 1: 16 t 2 weeks, while 8 weeks fter reimmuniztion the titres hd dropped to 1: 4 (17). In 6-month follow-up study of 19 children fter reimmuniztion, Bss et l. reported tht the neutrlizing ntibody titres of nine of the children decresed to pre-reimmuniztion levels (18). Finlly, Desd-Tous et l. reported tht 14 children who hd no detectble SIgM fter immuniztion (regrded s reimmuniztion) exhibited n HI ntibody geometric men titre of 1: 28, three weeks fter immuniztion, nd tht 1 months lter in 11 smples of serum the titre hd decresed to 1: 9 (19). * The results of the present study suggest tht mesles reimmuniztion produces n nmnestic rection. This provides strong evidence tht effective immunity is provided by one dose of mesles vccine nd demonstrtes tht booster dose is not necessry for persons who hd successful primry immuniztion ginst mesles up to 15 yers previously. The presence of low HI ntibody titre does not necessrily indicte the need for reimmuniztion, since children with low ntibody titres were not susceptible to clinicl infection with mesles. The points outlined below should nevertheless be considered crefully. * The proportion of those who becme seronegtive incresed with the intervl fter primry immuniztion. 422 * Clinicl cses of mesles occurred mong some successful vccinees, lthough such cses were rre nd of mild severity. * Neutrlizing ntibody ws not found in ser from 1 primry vccinees in whom HI ntibody ws undetectble for more thn 1 yers. * The immunity resulting from nturl infection with mesles virus differed from tht produced by immuniztion (s indicted by NT nd HLI ntibody responses) lthough the HI ntibody ptterns were similr in both cses. The bove points indicte tht primry immuniztion cn produce long-term immunity ginst mesles, but not necessrily life-long protection. The results shown in Tble 8 indicte tht there were differences in the durtion of immunity mong children depending on whether they were infected cliniclly, subcliniclly, or were reimmunized. After clinicl infection, the ntibody levels were higher nd more persistent thn fter reimmuniztion. Four cliniclly infected ptients not only hd high HI ntibody responses but lso hd very high HLI ntibody titres ( ) 1 month fter infection. This pttern of ntibody rection ws not simple nmnestic rection but profound immuno-trnsformtion, nd is probbly n importnt indiction of mesles immunity. It might be expected to produce longer-lsting effects if better ntigenic strins of mesles vccine re used. The overll results of the study indicte tht the immunogenicity of the two Chinese vccines (Hul91 nd Chng47) ws comprble with tht of the Schwrz strin. Altogether, 1.5%, 9.8% nd 11.9%, respectively, of ptients becme seronegtive following dministrtion of the Hul9l, Chng47, nd Schwrz vccines 14 yers fter primry immuniztion, with the HI ntibody titres beginning to convert to negtive between the 3rd nd 6th yers fter immuniztion. For L-16 vccine the rte t which ptients becme seronegtive incresed to 16.7% fter 14 yers. The HI ntibody titre of children who received primry immuniztion with the L-16 vccine becme seronegtive from the second yer fter immuniztion. Acknowledgements The study ws supported by the Ministry of Public Helth nd by the leders of the six collbortive units s well s hundreds of ssistnts, ll of whose contributions re grtefully cknowledged. We lso thnk Dr Li Hemin nd Dr Wng Tiking for directing the study nd correcting this rticle.

9 Durtion of immunity produced by live mesles vccine in Chin Resume Duree de l'immunite pres vccintion ntirougeoleuse pr un vccin vivnt: 15 ns d'observtion dns l province de Zhejing, Chine L duree de l'immunite pres vccintion ntirougeoleuse de 2882 enfnts ete 6tudi6e pendnt 15 ns dns une r6gion fermee de l Chine. Pour 12 de ces enfnts, il s'gissit d'une primovccintion, et pour 1547 utres d'une revccintion. Ces deux cohortes n'ont eu ucun contct vec un virus rougeoleux vivnt connu pendnt toute l duree de l periode d'observtion, et les r6sultts obtenus refletent probblement les reponses en nticorps u seul vccin ntirougeoleux. Les 333 sujets restnts sont entr6s en contct vec le virus rougeoleux suvge, ce qui permis d'evluer l'effet protecteur du vccin utilis6: 4 enfnts ont eu une rougeole tres l6gere, et 329 une infection infrclinique, dont 12 cs qui pendnt 9 1 ns n'ont eu ucun nticorps d6celble pr inhibition de l'hemglutintion. Ces r6sultts indiquent que l'immunit6 induite pr une primovccintion reussie peut durer u moins 15 ns. Pendnt cette periode, I'dministrtion d'une deuxieme dose de vccin n'induit que de fibles reponses en nticorps, qui retombent rpidement leur tux d'origine. Cel confirme l durbilite de l'immunite due l primovccintion. Toutefois, quelques observtions semblent indiquer que l revccintion pourrit voir un effet plus sensible si on utilisit un vccin ntirougeoleux vivnt ttenue, en esp9nt dvntge les doses. References 1. Zhuji Collborting Unit for the Observtion of the Vccine. [Studies on the durtion of immunity provided by ttenuted mesles live vccine l: results of ntibody responses 5 yers fter primry vccintion]. Ntionl medicl jouml of Chin, 6: 1-4 (198) (in Chinese). 2. Zhuji Collbortive Unit for the Observtion of the Vccine. [Observtion on the clinicl rection nd immunities produced by four strins of mesles live vccine]. Ntionl medicl journl of Chin, 6: 4-9 (198) (in Chinese). 3. Zhuji Collbortive Unit for the Observtion of the Vccine. [Observtions on the results of revccintion of mesles live vccine]. Ntionl medicl journl of Chin, 6: 9-13 (198) (in Chinese). 4. Zhuji Collbortive Unit for the Observtion of the Vccine. [Results of 9 yers since primry inocultion]. Ntionl medicl journl of Chin, 63: (1983) (in Chinese). 5. Zhuji Collbortive Unit for the Observtion of the Vccine. [The persistence of immunity fter primry immuniztion with four strins of mesles live vccine]. Ntionl medicl journl of Chin, 63: (1983) (in Chinese). 6. Zhuji Collbortive Unit for the Observtion of the Vccine. [Observtions on the results of revccintion with different vccines nd by different routes]. Ntionl medicl journl of Chin, 63: (1983) (in Chinese). 7. Zhuji Collbortive Unit for the Observtion of the Vccine. [Epidemiologicl exmintion of the durtion of immunity of mesles vccine]. Ntionl medicl journl of Chin, 67: (1987) (in Chinese). 8. Zhuji Collbortive Unit for the Observtion of the Vccine. [An investigtion on mesles epidemic condition in Zhuji County: the group investigtion of mesles vccine immunity durtion]. Chinese journl of epidemiology, 8: (1987) (in Chinese). 9. Fng Hnhu. Comprison between HI nd NT ntibody fter vccintion. Journl of biologicls, 3(1): 37-4 (199). 1. Krugmn, S. et l. Further ttenuted mesles vccine: chrcteristics nd use. Reviews of infectious diseses, 5: (1983). 11. Miller, C. Live mesles vccine: 21 yer follow-up. British medicl journl, 295: (1987). 12. Pedersen, I.R. et l. Long-term ntibody response fter mesles vccintion in n isolted Arctic society in Greenlnd. Vccine, 4: (1986). 13. Isomur, S. et l. A long-term follow-up study on the efficcy of further ttenuted live mesles vccine: Biken CAM vccine. Biken journl, 29: (1986). 14. Linnemnn, C.C. et l. Mesles immunity fter revccintion: results in children vccinted before 1 months of ge. Peditrics, 69: (1982). 15. Blck, F.L. et l. Indequte immunity to mesles in children vccinted t n erly ge: effect of revccintion. Bulletin of the World Helth Orgniztion, 62: (1984). 16. Di Bin, et l. [Study on the hemolysis-inhibition ntibody produced fter immuniztion of live mesles vccine]. Chinese journl of microbiology nd immunology, 2: 8-85 (1982) (in Chinese). 17. Krugmnn, S. Present sttus of mesles nd rubell immuniztion in the United Sttes: medicl progress report. Journl of peditrics, 9: 1-12 (1987). 18. Bss, J.W. et l. Booster vccintion with further live ttenuted mesles vccine. Journl of the Americn Medicl Assocition, 235: (1976). 19. Desd-Tous, J. et l. Mesles revccintion persistence nd degree of ntibody titre by type of immune response. Americn journl of diseses of children, 132: (1978). 423