AD-769 364

EVALUATION OF GROUP C MENINGOCOCCALPOLYSACCHARIDE VACCINE IN MARINERECRUITS, SAN DIEGO, CALIFORNIA

Leonard F. Devine, et al

Naval Medical Research Unit No. 4Great Lakes, Illinois

29 December 1969

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04IspNNT TITLE

Evaluation of Group C Meningococcal Polysaccharide Vaccine in Marine Recruits,SnDiego, California

J, Filial8. AUVW60) aL."# amum an# awme mawe

NDevine, L. F. , Pierce, W. E. Floyd, T. M. , Rhode, S. L. , Edwards , E. A.Sless, E. E., and Peckinpaugh, R. 0.

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Group C meningococcal polysaccharide vaccine was well tolerated by3,018 vaccinated Marine recruits. The vaccine appeared to be group-specific since it prevented the acquisition of only group C meningococci.The vaccine stimulated a good hemagglutinating antibody response, butdid not stimulate a comiplement fixing antibody response. One systemicillness of uncertain etiology, possibly vaccine related, vw observedamong the vaccinees. That the vaccine affords protect ion againstclinical disease was suggested when three cases of meningococcal diseaseof group C etiology developed in the nonvaccinated controls thile noneoccurred among the vaccinated men of the study population.

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EVALUATION OF GROUP C MENINGOCOCCAL POLYSACCHARIDEVACCINE IN MARINE RECRUITS, SAN DIEGO, CALIFORNIA'

LEONARD F. DEVINE', WILLARD E. PIERCE', THOMAS M. FLOYD'SOLON L. RHODE', EARL A. EDWARDS, EUGENE E. SIESS'

AMD ROBERT 0. PECKINPAUGH'

(Received for publication December 29, 1969)

Devine, L. F., W. E. Pierce, T. M. Floyd, S. L. Rhode, E. A. Edwards, E. E. Siessand R. 0. Peckinpaugh (Naval Medical Research Unit No. 4, Great Lakes,Illinois 60088). Evaluation of group C meningococcal polysaccharide vaccine

in Marine recruits, San Diego, California. Amer. J. Epid., 1970, 92: 25-32.-

Group C meningococcal polysaccharide vaccine was administered to 3,018

Marine recruits. The vaccine appeared to be group-specific since it preventedthe acquisition of only group C meningococci. The vaccine stimulated a good

hemagglutinating antibody response, but did not stimulate a complement fixingantibody response. One systemic illness of uncertain etiology, possibly vaccinerelated, was observed among the vaccinees. That the vaccine affords protection

against clinical disease was suggested when three cases of meningococcaldisease of group C etiology developed in the nonvaccinated controls while noneoccurred among the vaccinated men of the study population.

antibodies; carrier state; complement fixation tests; hemagglutination inhibitiontests; meningococcal infections; Neisseria meningitidis; recruits; vaccine, group C

meningococcal polysaccharide

Until recently, attempts to develop an epidemic emergencies have met with lira-effective meningococcal vaccine for use in ited success. Lepeysonnie, in 1963 (1), has

reviewed the generally disappointing ex-'From Naval Medical Research Unit No. 4

(NAMRU-4), Great Lakes, Illinois and Preven- perience with immunization against me-tive Medicine Unit No. 5 (PMU-6), San Diego, ningococcal disease in Africa between 1915Calif. This study was eine in connection with and 1950. However, improvements in ourResearch Project No. M4305.01-1016B, Bureau of understanding of natural immunity to me-Medicine and Surgery, Navy Department, Wash.,D. C. The opinions and assertions contained ningococcus (2, 3) and the recent develop-herein are those of the authors and are not to be ment of immunogenic group-specific me-construed as official or as reflecting the views of ningococcal polysaccharide vaccines havethe Navy Department or the Naval Service atlarge. The use of commercially available products Preventive Medicine Unit X5, San Diego, Calif.:does not imply endorsement of, nor preference LCDR Richard L. Nail, MC USN, HMC M. J.for the products. Amos, HM1 L. F. Parsons, HM3 D. Rullcoaki,

Reprint request to; Commanding Officer, HM3 M. Thompson, HM3 D. McLeod and HM3Naval Medical Research Unit No. 4, Great G. P. Bond for technical assistance; to the per-Lakes, Minois M008. sonnel of Naval Medical Research Unit No. 4,

'Chief, Bacteriology Division, NAMRU4. Great Lakes, Illinois: Mr. G. L. Larson, HMC D.'Chief, Biometrics Division, NAMRU-4. J. Seibhrt, HMI J. Hannah, HM2 D. Mueller'Bacteriologist, PMU-6, San Diego, Calif. and Miss P. Muehl for technical and field assist-*Epidemiology Division, NAMRU-4. ance; to HM2 D. C. Herman and Mrs. B. Kubik'Chief, Immunology Division, NAMRU4. for biometric assistance; and to Mr. C. E.'Officer in Charge, PMU-5, San Diego, Calif. Knight, Mrs. L. M. Duggan and Mrs. P. C.'Commanding Officer, NAMRU-4. Warren for assistance in preparation of the manu-The authors are indebted to the personnel of script.

25

26 DEVINE XT AL.

improved the prospects for interrupting camp did not permit separation of platoonsthe spread of meningococci in populat'ons or series. Hence, the men from variousat risk (4-6). An opportunity to further platoons and series commingled freely inevaluate the group C polysaccharide vac- the fifth and sixth week of training. Dur-cine of Gotschlich et al. (4) occurred at ing the study, routine immunization andthe Marine Corps Recruit Depot prophylactic procedures were continued(MCRD), San Diego, Califorria in April, without interruption. Included were sul-1980. Clinical cases of meningococcal dis- fisoxazole 1 gm twice daily by mouth forea&ie caused by group C meningococci be- two days upon arrival (to eliminate sul-gan to occur frequently in Marine recruits fadiasine-sensitive meningococcal strains)at MCRD during 1968. There were 16 and benzathine penicillin G 1,200,000 unitsbacteriologically confirmed cases caused intramuscularly in the second week ofby group C meningococci in that year. training (to eliminate and prevent subse-Twenty more cases caused by the same quent acquisition of group A streptococci).serogroup occurred in the first four months Platoons were randomly preselected toof 1969. Extensive meningococcal surveys be vaccinated or to remain untreated asconducted in March and April, 1969, vaccine controls. Selections were made byshowed that the group C carrier rate one of che authors (WEP) using a table ofamong recruits regularly increased from 5 random permutations. Half of the platoonsper cent at the beginning of training to in each series were vaccinated. Thus, eachmore than 40 per cent four weeks later, treated platoon has a preselected controlAccordingly, the decision was made to ad- platoon within the same series. On theminister meningococcal polysaccharide second day after arrival at MCRD, allvaccine to a portion of volunteers corn- volunteers in the platoons selected formencing Marine recruit training to deter- vaccination received 0.5 ml of meningococ-mine the effect of vaccine on the spread of cal vaccine" (6) (50 Ig group C polysac-nasopharyngeal meningococci. charide) in the right deltoid area using a

jet hypo spray gun (Scientific EquipmentMATZBAL•S Am)D MErHoDs Manufacturing Corp., New York, N. Y.).

The study population consisted of all Only two men failed to volunteer. Pairs ofMarine recruits entering training at the vaccinated and control platoons wereMCRD from April 28 to June 4, 1969. randomly selected (as described above)Approximately 1,000 men arrived weekly for nasopharyngeal cultural surveys.for eight weeks of basic training. Each Three pairs of platoons were selected perday, arrivals were divided into platoons week for nasopharyngeal culturing fromconsisting of 75 to 80 men. Four consecu- the first two weeks of input and two pairstive platoons constituted a training series. froin the following four weeks of input.Each series of platoons was assigned to The men in each platoon selected had aone of the three battalions. Each battalion total of five cultures approximately tworeceived at least one or more series of weeks apart. Scheduling difficulties re-platoons per week. The first four weeks of suited in slightly irregular periods as

training were accomplished at the MCRD. shown in table 1. Nasopharyngeal culturesThe integrity of each platoon was main- were taken from all men in the platoonstained during these four weeks and the op- selected for the cultural survey immedi-portunity for contact with other platoons ately before receiving sulfisoxazole on thewas minimal. The men were relocated inanoter ampat te ed o thefouth Group C polyseceharidc vaccine, lot No. C-7,

another camp at the end of the fourth furnished by Walter Reed Army Institute of Re-week for two weeks of training on the search, produced under contract by E. R. Squibbrifle range. The berthing facilities at this and Sons, Inc.

4, . .. -

EVALUATION: MZNINoOo<CCAL VACCINE IN MARINE DURUITS 27

morning of the second day after arrival at and meningococci isolated and identifiedMCRD. The second culture was taken be- as previously described (7) except thattween 14 and 21 days later. The three sub- sulfadiazine sensitivity was determinedsequent cultures were taken 9, 33 and 41 by inoculating Mueller-Hinton plates con-days, respectively, after the second cul- taining 1 ng per cent of sulfadiazine.ture. Each week initial blood specimens Meningococci growing on this media werewere collected from all men in one pair of considered to be resistant to sulfadiazine.platoons when initially cultured. Addi- The slide agglutination test was performedtional blood specimens were collected from using locally prepared group-specific rab-the same men when the second and last bit antiserum. Meningococcal groupingcultures were taken. Continuous monitor- antisera were absorbed with a strain ofing of outpatient visits and hospital ad- meningococci (RAS-10) which shares an-missions of all men in the study was per- tigens of several serogroups, as previouslyformed to detect any adverse reactions to described (8). The reliability of serologiethe vaccine or any evidence of meningo- identification was thereby improved. Thecoccal disease. hemagglutinating (HA) antibody tests

Nasopharyngeal cultures were taken were performed by the methods of Ed-wards and Driscoll (9) and the comple-

TABia 1 ment-fixation (CF) test by the methods ofSchem of netw and tise" Edwards and Devine (10).etsan dan Median day REsuLTn

]•vmte P~tat v wim~m Poat vaccnatif

Cultur-l, lotsrum 0 0 The group C meningococcal polysac-vaccination charide vaccine was administered to 3,018

Culture-2, 2nd serum 14-21 17.5 Marine recruits. The effect on the carrierCultures 28-30 26.5 rates of the carious serogroups in vacci-Culture-4 47-4 50.5 nated and coLrol men at the times ofCultur-4, 3rd serum 55-0 8. cultures during the study is shown in

TABDL 2

Distribution of per cent of Marine recruit# positive for various meningococcal serogroups and sulfadiasinesensit ivities at various 8ampling periods

Per cat positive

No. ofTmatment man C RAS-100 Boe ~ Otrt Total

Semm Res.: Sew. Re. Sens. Rea. Sees. Re& Seat. Res. Sees. Re.

1 Vaccine 1056 1.6 1.8 10.4 0.4 4.0 0.6 4.6 0.6 2.8 0 23.4 3.3Control 1058 0.9 1.4 9.8 0.9 3.3 0.8 4.2 0.3 2.6 0 20.8 3.4

2 Vaccine 934 1.5 3.5 3.7 2.7 1.3 1.3 1.2 0.4 0.7 0.2 8.6 8.1"Control 946 0.8 5.3 3.6 2.0 2.2 1.4 1.3 0.2 0.6 0.3 8.6 9.2

3 Vaccine 876 1.1 4.9 4.8 5.3 1.8 1.7 1.7 0.3 1.3 0 10.8 12.1Control 903 0.8 9.9 5.0 3.2 2.2 2.0 1.7 0.4 1.1 0.2 10.7 15.7

4 Vaccine 813 2.1 7.7 5.4 10.3 4.6 2.2 1.7 0.5 1.1 0.5 14.9 21.3Control 841 1.4 20.8 3.6 9.3 3.4 3.9 1.8 1.5 1.8 0.5 12.0 36.0

5 Vaccine 791 1.0 8.0 3.3 13.0 6.2 2.7 1.0 0.4 3.2 0.6 14.7 24.7Control 822 1.2 21.4 3.2 13.4 3.2 4.3 2.2 0.9 2.4 0.5 12.2 40.4

"Reacts to 2 or more sera.t 29E, Z, non-typable.t Seos- sulfadiaaine-eensitive; Res. - sulfadiuine-resistant.

28 Dnvnmr 19T AL.

60( platoons at the time of the first two cul-TA ISOLATNS tures was not statistically significant. A

comparison of the isolations, using theanalysis of variance, showed that signifi-

TOTL IStAXMs cantly more group C strains were isolatedf 40the control men at the time of the

/ S third, fourth and fifth cultures than fromISOtLtn0NS OTHER

THAN GROUP C the vaccinated men (p = <0.05).CONTROLS The data in table 3 show the number of

20 AMOK CONTROLSs men in vaccinated platoons and their con-trols acquiring group C meningococci after

GRUP C ISOLATIONS the second culture. Those included in thisAMONG. WMNEES table had five cultures taken. Comparison

0 can be made between pairs of vaccinated20 40 60 and control platoons entering training in

MEDIAN DAYS POST VACCINATION the same series. In 13 of 14 pairs of pla-

Fioum 1. Per cent of vaccinated and control toons, fewer vaccinated men acquiredmen carrying different meningococeal serogroupa group C meningococci after the secondat median times following vaccination, culture than did their controls.

Sera from 20 individuals in each of sixtable 2. Initially, the distribution of me- vaccinated and six control platoons wereningococcal carrier rates in the serogroups selected for a serologic survey. A series ofand their sulfadiazine sensitivities were three sera was drawn from these men atnot significantly different between men in the time of the first, second and fifth cul-the vaccinated and control platoons. The tures (table 1). Group C specific HA andmajority of the meningococcal strains iso- genus specific CF tests were used to de-lated on the first culture from all of themen were sulfadiazine sensitive. The effect TABL. 3

of sulfisoxazole prophylaxis is apparent Numbers and per cents of man acquiring group Cfrom these data. Thcre was a marked re- meningococci after second culture in paired

duction in carrier rates of sulfadiazine- vaccinated and control platoons

sensitive organisms at the time of thesecond culture. Group C meningococci No. Group C isolates Group C isolate

were initially the most prevalent sulfadi- men m n o

azine-resistant serogroup, and as would be No. (%)expected, remained the most prevalent or- 44 6 (13.6) 61 35 (57.4)ganism throughout the study. 60 2 (3.3) 51 26 (51.0)

The cultural data are summarized in 47 6 (12.8) 59 20 (33.9)51 11 (21.6) 57 18 (31.6)

figure 1 and show the effect of vaccination 59 3 (5.1) 56 14 (25.0)

with group C polysaccharide on the me- 37 2 (5.4) 33 12 (36.4)ningococcal carrier rates. There was a re- 49 0 (0.0) 55 11 (20.0)

duction in the meningococcal carrier rate 45 6 (13.3) 60 11 (18.3)

after the second culture in the vaccinated 58 1 (1.7) 66 11 (16.7)52 4 (7.7) 56 f (16.1)

men when compared to the controls. The 61 6 (9.8) 54 8 (14.8)vaccine reduced the rate of acquisition of 57 3 (5.3) 51 6 (11.8)group C meningococci and had no effect on 54 0 (0.0) 46 1 (2.2)

the acquisition rate of other serogroups. 58 8 (13.8) 59 1 (1.7)

The difference in per cent of men carrying (7.9) 183 (24.0)

group C in the vaccinated and control 732 58_(7.__764 _18 _(2_.0

EVALUATION: M•NINGOCOCCAL VACCINE IN MARINE RECRUITS 29

TABLE 4 Table 5 summarizes the cultural andNumbers of vaccinated or control men not carrying serologic results in vaccinated and controlgroup C meningococci at the onset of th.. 9udy who subjects during the study. Twenty-six ofsubsequently developed a fourfold or greater 34 control men who became carriers ofserologic rise at either the time of the second

or third serum sample group C developed a fourfold HA antibodytiter rise to group C. Five of 31 control

Stest Treat- No. of samp3* d senam men who developed a fourfold HA anti-Serolo-ico. ot sample° ssmplett met me No. M) No. (%) body titer rise did not become carriers of

-•group C at any time. Thus, eight carriersHeagttiato Vaoe 116 1,3 (97.4) 0 (0.0) of group C failed to develop a significant

(omopC) ont le 0 (.0) a5 2') HA antibody titer rise to group C. OnlyComnplenment 9as- Vacine 118 0 (0.0) 8 (5.2)

lion Control 119 0 (0.0) 26 (21.S) four vaccinated men who had a group C

14-21 days post vaceinati , on. -HA response to the vaccine subsequently55-4 da" post vaccination, acquired group C. None of the vaccinated

men developed at. additional significanttermine fourfold or greater antibody rises, antibody rise to group C at the time of theThe results summarized in table 4 include third serum sample. In those men who de-only data obtained from sera of individ- veloped fourfold HA antibody rises fol-uals who were noncarriers at the beginning lowing vaccination, the geometric mean ofof the study. Fourfold or greater HA anti- the reciprocals of their titers was increasedbody titer rises were found in 97.4 per cent from 2.1 to 82.7. These titers ranged fromof the sera of vaccinated men at the time 1:16 to 1:2040.of the second serum sample in cc utrast to One vaccinee had a gradual onset of2.5 per cent of the sera taken .rom the polyarthritis and fever which became in-nonvaccinated controls. The prevaccina- capacitating with bilateral effusion oftion HA antibody titers of the three vac- knees by the third day after vaccination.cinated men who failed to develop a sig- Because of a holiday weekend, he did notnificant rise were <1:2, 1:8 and 1:256. rece've any other immunization or sulfis-Two of the three control men who had de- oxazole. He was hospitalized for a periodveloped significant HA antibody titer risesto group C between the first and second TABLE 5

sera, had become carriers of group C by Relationship of 4-fold or greater serologic rise and

the time of the second serum sample. Sig- acquisition of group C meninqococcusin vaccinated and control men

nificant rises in HA antibody titer to group i -ciaeancotlmn

C occurred in 23.6 per cent of 119 control No. of mensubjects betw een the second and third Ac u st o a ci a e o t oserum samples. This is consistent with the Acquisition Vaccinated Controltime and magnitude of acquisition of C r 1 418CF" and HAt re- 1 18

group C among controls as shown in figure sponse1. Although 97.4 per cent of the vaccinated HA only 3 8

and 2.5 per cent of the control men de- CF only 0 1veloped a significant rise in HA antibody No seroresponse 0 7

titer to group C in the second serum sam- Group C 112 85

pie, none of these men developed a signifi- CF and HA response 5 5cant rise in CF titer. Subsequently, in the HA only 1G.0 0third serum sample 21.8 per cent of the CF only 0 2control men and 5.2 per cent of the vac- l t seroreaponse 3 78cinated men developed significant CF an- s Complement fixation.tibody titer rises. t Hemagglutination.

30 DEVINE Nr AL.

TAxBu 6 Three cases of clinical meningococcal dia-The reults of waop/aryngeal me.inacoccal cul- ease occurred among the more than 3,000

turu taken, from three msn who subsequently controls and no cases developed among adewZclped group C clinical mmitis similar number of vaccinees. The vaccine

DayDay was well tolerated with the exception ofSub- Priys Result = Rul D' Resmlt one person who developed an atypical ill-jucts to to

o.... oust 0 5 ness of uncertain etiology.

RP Netive 2 t 4 G rupC Nasopharyngeal cultures were takenis 21 Neative s Ooup C from the three men in the control groupLX[ 13, Negativ 4 Negatve who subsequently developed clinical me-

ningococcal disease. Two of these men be-of 15 days with complete resolution of all came carriers two or more days beforesigns and symptoms without specific ther- onset of symptoms. The third was not aapy. Meningococci were not isolated from carrier four days prior to illness. The sig-the nasopharynx on the third or 21st day nificance of protecting certain individualspost vaccination. Serum collected on the from acquiring meningococci is suggestedthird day after vaccination had neither by these data.HA nor CF meningococcal antibody titers, The sulfisoxasole prophylaxis programbut the group C meningococcal HA anti- temporarily effected a significant reduc-body rose to 1:32 by the 21st day after tion in the meningococcal carrier rate dur-vaccination. Antistreptolysin 0 titers ob- ing the first two weeks of training. How-tained on the third, sixth, 21st and 73rd ever, by the time of the third culture, sul-days post vaccination were 96, 128, 384 fadiazine-resistant group C meningoooc-and 256 Todd units, respectively. How- cal strains became the most prevalentever, it was not considered that patho- group and continued to be so among con-genesis of the fever and arthritis were trol men throughout the study.definitely established in this case. No other An apparent effect of vaccination withlocal or systemic reactions were noted group C polysaccharide was the inhibitionamong any other vaccinees. of the acquisition of group C meningococci.

There were three cases of meningococcal This vaccine was obviously group-specificmeningitis among the men in the control as evidenced by the nearly identical ac-platoons in this study population. Each quisition of meningococci of all otherwas of group C etiology. All of the cases serogroups among vaccinated and controlfortuitously occurred in platoons prese- subjects. Gotschlich et al. (6) suggestedlected for the cultural survey. Table 6 that the reduction in acquisition of groupshows the nasopharyngeal cultural results C by vaccination may be offset by an in-of the patients at various times prior to crease in the prevalence of meningococci ofonset of clinical disease. other serogroups. This was not observed in'

this study, although only half of the in-DiscussioN coming recruits were vaccinated for a pe-

A group C meningococcal polysaccha- riod of only six weeks while other sero-ride vaccine administered to Marine re- groups wore prevalent.cruits was effective in reducing naso- There were marked variations betweenpharyngeal acquisition of group C menin- platoons in the number of group C acquisi-gococci. The vaccine elicited a good HA tions in this study. However, in 13 of 14antibody response to group C in 97 per pairs observed, the men in the vaccinatedcent of the vaccinated men but failed to platoons had fewer acquisitions of groupstimulate the production of CF antibody. C. The overall reduction in the acquisition

EVALUATION: MEKINGOCOCCAL VACCINE IN MAmINE RECRUITS 31

of group C by culture in the men in the tors to consider before acceptinig this vac-vaccinated platoons was 67 per cent, cine in routine control of disease. Con-which offsets the platoon variations. sideration must be given to the fact that

Significant HA meningococcal antibody this vaccine is clearly group-specific.rises to group C occurred in all but three Cultural surveillance will determine theof 116 vaccinated men within two to three ecological consequences of group-specificweeks after vaccination but none of these vaccination. Continued use of this vaccine116 men developed CF antibody titer rises in a unique environment such as a militaryduring this time. There were no significant recruit camp could well give meningococciCF antibody rises in the final serum sam- of other serologic groups a selective ad-ples of any men in eimer group in the ab- vantage in spreading. The use of a poly-sence of the carrier state. Twenty-six of valent vaccine would overcome this poten-119 control men and only six of 116 vac- tial drawback if it should be observed.cinated men developed significant rises in Historically in military populations,CF antibody titers following the subse- meningococcal disease has been primarilyquent acquisition of one of the serogroups a recruit disease. This is partially ex-of meningococci. The number of CF re- plained as the result of the interminglingsponses following acquisition of other sero- of large numbers of susceptible men. Re-groups of meningococci was the same in cruits may become "seasoned" by devel-vaccinated and control men. The difference oping protective antibodies during naso-noted in total CF response between vac- pharyngeal infections. These antibodiescinated and control subjects is due to the apparently give long-term protection. Itdifference in the acquisition rates of group would be important to know if protectionC in the two populations. These data sug- of comparable degree and duration cangest that the CF test may be a useful tool also be achieved by vaccination.for estimating the efficacy of this menin- Rmmcxsgococcal vaccine in reducing total menin- 1. Lepeyinonnie, L. La m~ningite crbro-opinalegococcal acquisitions or infections. The en Afrique. World Health Organizationrelative reduction of CF response associ- Bulletin 28, Supplement, 1963.ated with vaccine in this study was 76 per 2. Goldschneider, I., Gotachijo, E. C. andcent and is only slightly greater than the Artenatein, M. S. Human immunity to thereduction in acquisition of group C menin- meningococcus. I. The role of humoral

antibodies. J. Exp. Med., 1969, IN*: 1307-gococci observed by culture. 1328.The vaccine appears to be potentially 3. Goldschneider, I., Gotschlich, E. C. and

useful in the control of group C meningo- Artenatein, M. S. Human immunity to thecoccal disease. The prophylactic effect of meningococcus. H. Development of naturalimmunity. J. Exp. Med., 1969, 129: 1327-this vaccine, however, cannot be com- immui. .pared to the effect of sulfonamide prophy- 4. Gotechlich, E. C., Liu, T. Y. and Artenstein,laxis. Sulfonamides eliminate the carrier M. S. Human immunity to the meningo-state, whereas, the vaccine prevents ac- coccus. HIL. Preparation and immunochemi-quisition of meningococci. Furthermore, cal properties of the group A, group B and

group C meningococcal polysaccharides. J.the effect of vaccination is 'ieiayed until Exp. Med., 1969, 12: 1349-4M.antibodies develop. Therefore, when epi- 5. Gotachlich, E. C., Goldschneider, I. and Ar-demic disease occurs in a recruit camp tenstein, M. S. Human immunity to theearly in training, the effect of vaccination meningococcus. IV. Immunogenicity ofon the epidemic may be limited and de- group A and group C meningococcal

polynccharides in human volunteers. J.iayed. Exp. Med., 1969,1*9: 1367-1384.

There are several other important fac- 6. Gotschlich, E. C., Goldschneider, I. and Ar-

32 DV NU AL.

tenatein1 hi. a. Human immunity of the ship of serogroups of Neiseria mnsngWitidis.meningococcus. V. The effect of immuniza- 1. Mficroagglutination, gel diffusion andtion with meningococcal group C polyinac- slide agglutination studies of meningococcalcharides on the carrier state. J. Exp. Med., antisera before and after absorption with1969,199: 1385-1396. RAS-10 strain of meningococci. Infect. Im-

7. Devine, L. F., Knowles, R.. C., Pierce, W. E., mun., 1970,1: 220-231.Peckinpaugh, &. 0., Hagerman, C. R.. sand 9. Edwards, E. A. and Driscoll, W. S. Group-Lytle, R. I. Proposed model for screening specific hemagglutination test for Nestseriaantmierobial agents for potential use in tneniVgiidis antibodies. Proc. Soc. Exp.eliminating meningococci from the naso- Biol. Med., 1967,106:8976-879.pharynx of healthy carriers. Antimicrobial 10. Edwards, E. A. and Devine, L. F. A genus-Agents and Chemotherapy-1968, 1969, pp. specific complement fixation antigen from307-314. Nesssevia meningitidia. Proc. Boo. Ebip. Biol.

S. Devine, L. F. and Hagerman, C. R.. Relation- Med., 1968, 108: 1168--1173.