Letters. Enhancement of response to vaccines and immunomodulators through carboxy-vinylpolymer couplings

References 1


3 4

Intranasal admlmstratton of mice with carboxy-vlnylpolymer (CVP) coupled to influenza A/Yamagata/120/86 (H1N1) strata vaccine sttmulates the greatest Immune response as measured by haemagglutmatmn-mh~bltlOn anttbody m serum, IgA and IgG antibody and neutrahzmg antibody in bronchopulmonary washtngs ~ The mvestlgatmns proposed here to ascertam the utdlty of CVP-coupled vaccmes for pertussls, dzphthena toxo]d and Japanese encephahtls in human beings should be pursued vigorously CVP forms a gel of htgh viscosity for omtments admmtstered intranasally and mtraocularly and has also been shown to be safe as a base for oral drugs As well as investigating the putattve utlhty of CVP m routme vacclnatmns durmg infancy and m pre-school aged children, the lncorporatton of CVP m rectal or vagmal supposttorles, used as carriers of epttopes to stimulate the mucosal tmmune system, may also be ascertamed For a meritorious performance, effective CVPbased supposttorles would be ideal for routine ~mmunlzatton during mfancy via the rectal or vaginal route, and also for immunlzatmn of pregnant females with tetanus and hepatltXS B m developmg countries 2 Such suppositories would ehmmate the risk of any latrogemc refection, including human ~mmunodefictency v~rus, through the use of madequately sterthzed syringes and needles tn the field Btologtcal response modttier therapy ts assoctated with the regulation and augmentatlon of the ~mmune response, a cytotoxtc or cytostatlc acttvtty towards cancer cells and mhzbmon of metastasis, dlfferentlauon or maturation ~ Almost every convenuonal route of admtmstratmn of therapeutic agents has been employed for the admlnlstratton of bmlogtcal response modifiers Therefore mvesttgattons should be performed to ascertain the feastbthty of CVP hnkage wtth dtfferent biological response modttiers In Afrtca, the use of mjecttons, which often mvolve unstertle equipment, for the treatment of sexually transmttted diseases are associated wtth the spread of a non-sexual hepatitis B4 Bemg very slmdar to vaccines, the parenteral rejections of lmmunomodulators could facthtate the dtssemmat]on of hepat]tts

0264~ 10X/91/090690-03 © 1991 Butterworth-HememannLtd 690

Vaccine, Vol 9, September 1991

B and human lmmunodeficlency vtrus throughout the community Regular use of CVP-hnked therapeutic agents, when avadable, would ehmmate insurmountable problems, such as multiple needle usage and inadequate stenhzatmn, during their field usage Stab,hty studtes on CVP-hnked vaccines or tmmunomodulators are tnd~cated to ehmmate the inadvertent failures hnked with the ngours of a field environment

Oka T, Hond, T Ohkuma, K, Sakoh, M and Nouako S Influenza vaccine enhancement of ~mmune response by apphcatlon of carboxywnylpolymer Vaccme 1990, 8 573-576 Arya, S C Specfftc tmmune response to vaccines m humans through stlmulabon of the common mucosal immune system Vaccine 1990 8, 613 Abernathy E B)otherapy an mtroductory overview Oncol Nurs Forum 1987, 14(6) 13-15 Hudson C P , Henms A J, Kataaha P e t a l R)sk factors for the spread of AIDS m rural Afrtca evtdence from a comparatuve seroeptdem~ologmal study of AIDS, hepatlbs B and syphdm m southwestern Uganda AIDS 1988 2, 255-260

S.C. Arya Centre f o r Loglsttcal Research and lnnovatton M-122, Greater K a d a s h - H N e w Delht-110048, Indta

Detoxification of Bordetella pertussis organisms or pertussis toxin with glutaraldehyde for preparation of pertussis vaccine A recent pubhcatton by Ruuskanen et al 1 prompts this response The authors have mentmned the new detox~ficatton procedure for pertussls toxin (PT) with glutaraldehyde but w~thout describing the detatls of the procedure The use of glutaraldehyde for detoxlficat]on of bactertal toxins including PT has already been described for preparatton of bacterial toxotds 2 6 The mactwatton of Bordetella pertussts orgamsms wzth glutaraldehyde for preparaUon of pertussts vaccine was described by Relyveld from the Instttut Pasteur almost 20 years ago 7 On the basis of hts ptoneer work on the detoxtficatmn of tetanus and diphtheria toxms with glutaraldehyde 34 8, whole cell pertuss]s vaccme was prepared by macttvatlon of B pertussts wtth glutaraldehyde 9 ,3 There are several reports on the detoxlficatmn of PT with gluraraldehyde 1'~-16 and glutaraldehyde-detoxlfled PT has already been proposed as a potential candtdate for acellular pertussts vaccme as such or along wtth other components of B pertussts 5 6 ~v Ruuskanen et al further stress that their new tOxoldmg procedure resulted m undetectable levels of actwe toxin and a stable PT toxold w~th wrtually no reverston It ts already reported that PT preparattons detoxtfied with gluraraldehyde do not

contam detectable levels of active toxin 6 and the toxold zs non-reversible18 Although the condtttons of detoxlficatton of PT wtth gluraraldehyde used by Ruuskanen et al, whtch have not been descrtbed, may be dtfferent from those descrtbed already, the use of glutaraldehyde for detoxificatlon of PT for preparation of acellular pertussts vaccine is not a new procedure as such

References 1





Russkanen O Noel, A Putto-Laurfla, A , Petre J Caplau C Delem A et al Development of an acellular pertussls vaccine and its admlnlstratton as a booster m healthy adults Vaccme 1991 9 117 Rappaport R S Bonde G McCann T Rubm B A and Trot H Development of a pur0f)ed cholera toxold II Preparat)on of a stable antigenic toxotd by reacbon of purffted toxin with glutaraldehyde Infect Immun 1974 9 304 Relyveld E H Current developments m production and testing of tetanus and chphtherla vaccines In New Developments with Human and Veterinary Vaccines (Eds Mizrahl A Hertman ) Khngberg M A and Kohn A ) P r o g Chn Btol Res Vol 47 Alan R L)ss New York 1980 pp 51 76 Reylveld E H and Ben-Efra)m S Preparatton of vaccines by the action of glutaraldehyde on toxins bacter)a, vtruses allergens and cells Methods Enzymol 1983 93 24 Chnstodouhdes M Pertuss)s vaccines Present status In Bacterial Vaccmes (Ed M)zrahJ A )










Advances m Btotechnologlcal Processes Vol 13, Wfley-bss New York 1990 pp 169 199 Gupta R K Saxena S N , Sharma, S B and Ahu)a S Production of a safe potent and immunogemc partially purified acellular pertuss~s vaccine using s~mple indigenous techtuques Paper presented at the International Symposium on Pertuss~s Evaluation and Research on Acellular Pertussts Veccmes Japan 14 15September 1990 Dev Biol Stand m press Relyveld E H Preparation de vaccins antitoxiques et anttmtcrobiens a I aide de glutaraldehyde C R Acad Scl Parts SertesD 1973 277 613 Relyveld E H Detoxfflcatlon of microbial toxins with glutaraldehyde and their use tn the preparation of vaccines In Toxins Animal Plant and Microbial (Ed Rosenberg P) Pergamon Press Oxford 1978 pp 1049-1065 Gupta R K Sharma S B Ahula S andSaxena S N The effects ot different reactivating agents on the potency toxicity and stabdfly of pertuss~s vaccine J Biol Stand 1987 18 87 hda T and Hortuch~ Y The detoxfftcat~on of Bordetella pertussm w*th glutaraldehyde J B~ol Stand 1987 15 17 Gupta R K Saxena S N Sharma S B and Ahuja S The potency toxicity and tmmunogemc~ty of g[utaraldehyde mact~vated pertussis vaccine Natl Med J India 1989 2 163 Gupta R K Saxena S N Sharma S B and Ahuja S Immunogemc~ty of glutaraldehyde inactivated pertussls vaccine Vaccine 1990 8 563 Gupta R K Use of glutaraldehyde for the preparation of pertussls vaccine Vaccine t990 8 409


Munoz J J Aral, H, Bergman, R K and Sadowskl P L Biological actiwt0es of crystalline pertusstgen from Bordetella pertussls Infect Immun 1981, 33 820 15 Cowell J L Sato, Y Sato, H, Lan, B A D and Manclark C R Separabon, purification and properties of the filamentous hemagglubnm and the leukocytosls promoting factor-hemagglutmm from Bordetella pertussts In Seminars in Infectious Diseases Vol IV Bacterial Vaccines (Eds Robbms J B Hdl J C and Sadofl J C ) , Thleme-Stratton Inc, NewYork 1982, pp 371 379 16 Robinson A and Hawkins D C Structure and biological properties of solubihzed envelope oroteins of Bordetella pertussls Infect Immun 1983 39 590 17 Robinson A and Ashworth L A E Acellular and defined-component vaccines against pertussls In Pathogenesm and Immunity in Pertussls (Eds Wardlaw, A C and Parton, R) John Wiley Chlchester, 1988 pp 399-417 18 Quentin-Millet M J Armtnjon F Danve B Cadoz M and Armand, J Acellular pertussts vaccines evaluahon of reversion m a nude mouse model J Biol Stand 1988 16 99

Rajesh K. Gupta Laholatol I o/Developmental and Mole~ ulal Immumtv, NICHD, National hlstttt~te~ o[ Health, BId,q 6, Room IA06, Bethesda, MD 20892, USA

Influenza vaccination acceptance among health care professionals Health care professionals (HCP) in close contact with hospltahzed high rtsk pattents, Including the elderly, are recommended for influenza tmmuntzatton m the United States ~, but their acceptance of the vaccine remains alarmingly low In the hope that knowledge of factors mhtbltlng HCP partlc~paUon m vaccine programmes could help to improve these rates, we conducted a survey among 62 randomly chosen medical personnel at the James A Haley Veterans' Hospttal Tampa, FL A written questionnaire was developed to determine influenza vaccination behavtour and reasons that influence its poslttve outcome Followup techniques were employed to obtain a 100% response rate Data were analysed 2 to tdentlfy the most common factors contributing to non-vacclnatton behavlour Only 12 out of 62 subjects (194%) indicated that they had received vacclnatron during the last year while 23 subjects (37 1%) had received the vaccme 1-5 years previously and 27 subjects (43 5%) had never recetved influenza vaccine Among the last group 13 subjects 148%) were physicians, nine subjects (33%) were nurses, two subjects (7%) chntcal laboratory and three subjects (11%) other support personnel The majority of the HCP (36 subjects 63%) surveyed lndtcated that they had close

contact with patients (a higher percentage among physicians and nurses) There was no difference m vaccination rates between the HCP with close patient contacts (19 4%) and those without (20%) (Table I) The most frequently ctted reason for lack of Immunization was that the HCP did not want the vaccine This amotlvatton was due to a multitude of factors lack of time in making the effort to get vaccinated, fear of side effects from vaccination, misconception about the vaccme efficacy and target groups, lack of mformation regardmg the easy availability of the vaccine at the VA chine free of charge, and perceived low risk of contacting influenza m medical settings Overall, fear of side effects and needle prick played a major role for non-

Table 1

compliance with influenza vaccine recommendation m less than one quarter (242%) of the non-comphant HCP When asked if the HCP knew somebody who suffered from influenza vaccine side reactions, 25 out of 58 HCP who responded said that they d]d (43%) Vaccine comphance rates between those that knew somebody who suffered from side effects of the vaccine and those that did not was not stattstlcally s~gmficant Nearly all physicians (17/18, 89%) and most of the clinical laboratory personnel (12/15, 80%) beheved that the vaccine benefits outweigh the side effects (Table 2a) The nurses were split almost equally on this issue (8/17 47% in favour) When risks of nosocomtal transmission or infection were considered, overwhelmmgly all categories of HCP indicated that thetr risk of mfectlon/transmisslon was no more than the general pubhc (67 7%) (Table 2b) Yet, over 74% of the HCP mdtcated that they had suffered from mfluenza-hke illness in the past (Table 2c) When asked if the flu shot should be taken yearly by the HCP, over half of the physlcmns and nurses were m favour of annual vaccination Physicians and nurses indicated also that they recommended influenza vaccination for their high risk pattents more physlctans (14/18 physicians) said they did (78%) than did the nurses (11/17 nurses, 65%) Results of this study reveal some dtsturbmg facts that prevent prophylactic comphance among the health care providers Amotlvatton is the most prevalent which reflects a discordance between knowledge and experience of the HCP and their personal preventive health practices This situation may be remedied by repeated dissemination of Information on vaccine efficacy and safety, reminders that the HCP in contact w~th htgh risk patients can transmit/ contact influenza and that easily accessible opportunity to be vaccmated, free of charge, ts avatlable at the VA hospitals Since most of the HCP think that the benefit of the vaccine outweighs risks from immunization and that it should be recommended for patients, these data indicate that the subjects do not act according to thetr knowledge/behefs when their own immunization behaviour ts concerned The HCP intellectually accept the influenza vaccine, but they do

Vaccination compliance among the health care professionals (HCP) and patient contacts Close patient contact

No close patient contact

HCP category

Comphant e



Physicians Nurses Clinical laboratory Other

2 1 2 2

8 14 2 5

0 0 4 0


7 (19 4%) °


4 (20%)

Non-comphant 3 1 6 6 16

56 HCP responded to this question aVacclnated in previous year a% Compliant tn respective groups

Vaccine, Vol 9, September 1991 691

Detoxification of Bordetella pertussis organisms or pertussis toxin with glutaraldehyde for preparation of pertussis vaccine.

Letters. Enhancement of response to vaccines and immunomodulators through carboxy-vinylpolymer couplings References 1 2 3 4 Intranasal admlmstratt...
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