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Vaccine Development and Collaborations: Lessons from the History of the Meningococcal A Vaccine (1969–73)

  • Baptiste Baylac-Paouly (a1) (a2)

Abstract

Based on a wide range of historical sources, including published scientific literature and archives (Institut Mérieux, WHO and IMTSSA), this article examines the history of the development of the meningococcal A vaccine between 1969 and 1973. It explores the social factors of vaccine development including various collaborations, informal discussions, the circulation of products and materials, formal meetings, trials and setbacks to highlight the complex reality of the development, production and use of the vaccine. Inscribed in a ‘Golden Age’ of vaccine development and production, this episode not only adds to the scholarship on the history of vaccines, which has tended to focus on a narrative of progress, but also considers the sharing of knowledge through collaborations, and the risks involved in the development of a vaccine. Finally, this perspective reveals the uncertainties and difficulties underlying the production of an effective vaccine.

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Corresponding author

*Email address for correspondence: baptiste.baylac-paouly@univ-lyon1.fr

Footnotes

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I would like to thank the Institut Mérieux, the World Health Organization and the Service Historique de la Défense – Division Sud-Est – Toulon for providing access to their archives, and especially to Reynald Erard at the WHO for guidance and assistance. I would also like to thank Jonathan Simon and Gareth Millward for their invaluable help in preparing the manuscript, and the three anonymous Medical History reviewers for their comments.

Footnotes

References

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1. Saliou, Pierre and Debois, H., ‘Quelles stratégies vaccinales contre les épidémies africaines de méningite à méningocoque’, Bulletin de la Société de Pathologie Exotique, 95, 5 (2002), 327.

2. Dutertre, J., ‘General Medical Officer Lapeyssonnie “The Man of Big Endemics”’, Bulletin de la Société de Pathologie Exotique, 95, 5 (2002), 307–9.

3. Lapeyssonnie, Léon, ‘À propos de la récente épidémie de méningite cérébrospinale au Niger. Activité d’une mission médicale française (3 mars 1961–7 avril 1961)’, Médecine Tropicale, 21, 2 (1961), 172–4.

4. Lapeyssonnie, Léon, ‘La méningite cérébrospinale en Afrique’, Bulletin of the World Health Organization, 28, suppl (1963), 1114.

5. Lapeyssonnie, Léon, ‘Étude épidémiologique comparée de la méningite cérébrospinale méningococcique dans les régions tempérées et dans la ceinture de la méningite en Afrique’, Médecine Tropicale, 28, 6 (1968), 716–17.

6. Faucon, R., ‘Bases de la prophylaxie antiméningococcique’, Médecine Tropicale, 28, 2 (1968), 162.

7. Martin, R. and Delaunay, A., ‘L’action du para-amino-phényl-sulfamide (1162F) dans les méningites purulentes à streptocoques et accessoirement à méningocoques’, Presse Médicale, 45 (1937), 1406–9.

8. Mérieux, Charles, Virus Passion (Paris: Robert Laffont, 1997) 168–9.

9. The vaccine was based on twenty-four strains killed by heat and isolated by different correspondents of the IMTSSA in different countries of the meningitis belt.

10. Lapeyssonnie, Léon, ‘De quelques problèmes pratiques posés par les essais contrôlés sur le terrain d’un vaccin antiméningococcique’, Médecine Tropicale, 30, 5 (1970), 625.

11. The disease represented a major problem for researchers and trials of prophylactic measures: it was almost impossible to predict where an epidemic would occur. It was also difficult to predict for any given area whether an epidemic would take place, making African meningitis epidemics appear capricious and insidious.

12. Faucon, R. and Zannotti, P., ‘La méningite cérébrospinale à Fès en 1966–67. I. La méningite cérébrospinale au Maroc’, Médecine Tropicale, 29, 2 (1969), 151–60.

13. CSMa epidemics were usually short, with an ascending and descending phase.

14. This period could be marked at the beginning by the John Enders’ success in growing a polio virus on a tissue culture in 1948. The early 1980s were profoundly transformed by dramatic changes (fall of the Berlin Wall, collapse of the Soviet Union, economic crisis, extreme ideological commitment to liberalisation and privatisation), which affected vaccine development.

15. Blume, Stuart, Immunization: How Vaccines Became Controversial (London: Reaktion books, 2017), 9091.

16. Karen L. Walloch, The Antivaccine Heresy: Jacobson v. Massachusetts and the Troubled History of Compulsory Vaccination in the United States (New York: University of Rochester Press, 2015); Christine Holmberg, Stuart Blume and Paul Greenough, The Politics of Vaccination: A Global History (Manchester: Manchester University Press, 2017); Blume, ibid.

17. Sanjoy Bhattacharya, ‘International Health and the Limits of its Global Influence: Bhutan and the Worldwide Smallpox Eradication Programme’, Medical History, 57, 4 (2013), 461–86; Dora Vargha, ‘Between East and West: Polio Vaccination across the Iron Curtain in Cold War Hungary’, Bulletin of the History of Medicine, 88, 2 (2014), 319–43; Gareth Millward, ‘A Disability Act? The Vaccine Damage Payments Act 1979 and the British Government’s Response to the Pertussis Vaccine Scare’, Social History of Medicine, 30, 2 (2016), 429–47; Gareth Millward, “‘A Matter of Commonsense’: The Coventry Poliomyelitis Epidemic 1957 and the British Public’, Contemporary British History, 31, 3 (2016), 384–406; Jeremy K. Ward, ‘Rethinking the Antivaccine Movement Concept: A Case Study of Public Criticism of the Swine Flu Vaccine’s Safety in France’, Social Science & Medicine, 159 (2016), 48–57; Farah Huzair and Steve Sturdy, ‘Biotechnology and the Transformation of Vaccine Innovation: The Case of the Hepatitis B Vaccines 1968–2000’, Studies in History and Philosophy of Biological and Biomedical Sciences, 64 (2017), 11–21; Mary Augusta Brazelton, ‘Engineering Health: Technologies of Immunization in China’s Wartime Hinterland, 1937–45’, Technology and Culture, forthcoming (2019).

18. Workshop on ‘Vaccination between Research, Health Politics, and Nation: Lessons learned from historical examples on vaccination campaigns and vaccination development’ held at the East Anglia University Medical School in Norwich, UK, in October 2013; Workshop on ‘Vaccines: Values, Present and Past’ held at the Uppsala University Department of History of Science and Ideas in Uppsala, Sweden, in November 2017.

19. Graham, Janice, ‘Ambiguous Capture: Collaborative Capitalism and the Meningitis Vaccine Project’, Medical Anthropology, 35, 5 (2016), 420.

20. Faucon, op. cit. (note 6), 162.

21. Faucon and Zannotti, op. cit. (note 12), 151–60.

22. Lapeyssonnie, op. cit. (note 10), 625.

23. Archives of the Institut Mérieux, box D11, D11_2, 3_08/06/67; Archives of the Institut Mérieux, box D11, D11_2, 5_21/11/67; Archives of the Institut Mérieux, box D11, D11_3, 2_11/03/69.

24. Archives of the Institut Mérieux, box D11, D11_1, 1_12/11/63.

25. Archives of the Institut Mérieux, box D11, D11_2, 3_08/06/67.

26. B. Cvjetanović, ‘Les vaccins antiméningococciques étudiés par l’Organisation Mondiale de la Santé: A. Les vaccins antiméningococciques’, World Health Organization, BD/CSM/68.9, II ème séminaire interrégional sur la méningite cérébrospinale, Niamey, 13–17 février 1968, Bobo-Dioulasso, 19–24 février 1968, 123.

27. Archives of the Institut Mérieux, box D11, D11_3, 1_04/03/69.

28. Until then, the meningococcal vaccines developed were based on the whole cell technique using several strains of meningococcus, killed by heat and alcohol.

29. In the field of biochemistry, the dalton represents the mass unit of atoms. By way of comparison, one protein amino acid represents about 110 Da, a protein greater than 12 kDa, and a DNA base with deoxyribose and phosphate (one nucleotide) about 330 Da.

30. Artenstein, Andrew W. and LaForce, Marc F., ‘Critical Episodes in the Understanding and Control of Epidemic Meningococcal Meningitis’, Vaccine, 30 (2012), 4702–4.

31. Gotschlich, Emil C., Liu, Teh Yung and Artenstein, Malcom S., ‘Human Immunity to the Meningococcus: III. Preparation and Immunochemical Properties of the Group A, Group B, and Group C Meningococcal Polysaccharides’, The Journal of Experimental Medicine, 129, 6 (1969), 1350–1.

32. Artenstein and LaForce, op. cit. (note 30), 4704.

33. Artenstein, M.S. and Gold, R., ‘Current Status of Prophylaxis of Meningococcal Disease’, Military Medicine, 135, 9 (1970), 735.

34. Artenstein, M.S., Gold, R., Zimmerly, J.G., Wyle, F.A., Schneider, H. and Harkins, C., ‘Prevention of Meningococcal Disease by Group C Polysaccharide Vaccine’, New England Journal of Medicine, 282, 8 (1970), 417–20.

35. Archives of the Institut Mérieux, box D11, D11_3, 2_11/03/69.

36. The Pharo, located in Marseille, was a centre created in 1966 by the WHO. The creation of this centre was an element of the research programme launched by the WHO to fight against the CSMa after the work of Lapeyssonnie. Lapeyssonnie’s team of the IMTSSA was the hard core of this centre.

37. Archives of the Institut Mérieux, box D11, D11_3, 4_11/06/69.

38. Archives of the Institut Mérieux, box D11, D11_3, 5_09/07/69.

39. Archives of the Institut Mérieux, box D11, D11_4, 1_11/07/69.

40. Archives of the Institut Mérieux, box D11, D11_4, 3_01/08/69.

41. Archives of the Institut Mérieux, box D11, D11_4, 4_25/08/69.

42. Lapeyssonnie, Léon, ‘Épidémiologie de la méningite cérébro-spinale à méningocoques: le point de vue de Sirius’, Médecine Tropicale, 43, 1 (1983), 12.

43. Faucon and Zannotti, op. cit. (note 12), 151–60.

44. Léon Lapeyssonnie and J.P. Digoutte, ‘La vaccination antiméningococcique: intérêt et conditions d’utilisation’, WHO unpublished document, 16 September 1963, 3.

45. Ghipponi, P., Darrigol, J. and Faucon, R., ‘Un problème d’épidémiologie pratique en Afrique sahélienne: recherche de porteurs rhinopharyngés de méningocoques’, Médecine Tropicale, 28, 4 (1968), 504.

46. Archives of the WHO, box C11-87-2, ‘Informal Meeting on Cerebrospinal Meningitis Organized by the WHO International Reference Center for Meningococci with WHO Participation – Marseille, September 1969’ (1969), 1.

47. Ibid., 2–3; The whole cell technique used in the past by the Institut Mérieux would never be used again.

48. Archives of the Institut Mérieux, box D11, D11_5, 1_22/07/69.

49. Archives of the WHO, box C11-181-15(A), ‘Collaboration Laboratory Study of Polysaccharide CSM vaccines’ (1974).

50. Greenberg, Louis, ‘A New Approach to Bacterial Vaccines’, Canadian Medical Association Journal, 89, 9 (1963), 396402.

51. Lapeyssonnie and Digoutte, op. cit. (note 44), 1.

52. Archives of the Institut Mérieux, box D11, D11_1, 1_12/11/63.

53. Archives of the IMTSSA, box 2013 ZK 005-500, ‘Letter to B. Cvjetanović from Louis Greenberg’, 9 September 1963.

54. Archives of the IMTSSA, box 2013 ZK 005-500, ‘Letter to B. Cvjetanović from Pierre Mercier’, 8 November 1963. The doctor, Pierre Mercier, was the deputy general secretary of the Institut Pasteur in Paris.

55. Archives of the WHO, box C11-181-10, ‘Grant to Institut Mérieux, Lyon, in respect of production of cerebro-spinal meningitis vaccine’ (1969).

56. Archives of the Institut Mérieux, box D11, D11_5, 1_22/07/69.

57. Archives of the Institut Mérieux, box D11, D11_7, 4_15/10/69.

58. Gotschlich, Emil C., Goldschneider, Irving and Artenstein, Malcom, ‘Human Immunity to the Meningococcus: IV. Immunogenicity of Group A and Group C Meningococcal Polysaccharides in Human Volunteers’, The Journal of Experimental Medicine, 129, 6 (1969), 13671384.

59. Saliou and Debois, op. cit. (note 1), 327.

60. Archives of the WHO, box C11-181-13, ‘Subvention à la Faculté Mixte de Médecine et de Pharmacie, Dakar, en vue d’études sur les vaccins contre la méningite cérébrospinale: étude immunologique des vaccins contre la méningite cérébrospinale à utiliser dans les essais sur le terrain’ (1970).

61. Archives of the Institut Mérieux, box D11, D11_7, 5_17/10/69.

62. Archives of the WHO, box C11-446-2SUD, ‘Proposed Field Trial of Cerebrospinal Meningitis Vaccine’ (1969).

63. Archives of the WHO, box C11-440-3(69), ‘WHO Inter-Regional Seminar on Cerebrospinal Meningitis Control – 1969’ (1969); Archives of the IMTSSA, box 2013 ZK 005-511, ‘Letter to Léon Lapeyssonnie from B. Cvjetanović’, 21 March 1969. Cvjetanović was the head of Microbial Diseases at WHO.

64. Archives of the WHO, op. cit. (note 62).

65. Archives of the WHO, op. cit. (note 62).

66. Archives of the WHO, op. cit. (note 62).

67. Archives of the WHO, box C11-181-9, ‘Subvention au Ministère de la Santé Publique et des Affaires Sociales, Koubala, Mali, en vue d’un essai pratique contrôlé d’un vaccin polysaccharidique contre les méningocoques du groupe A et étude sur les porteurs de méningocoques’ (1969).

68. Archives of the Institut Mérieux, box D11, D11_8, 3_31/10/69.

69. Archives of the Institut Mérieux, box D11, D11_8, 10_10/12/69.

70. Archives of the Institut Mérieux, box D11, D11_8, 11_10/12/69.

71. Ibid.

72. Archives of the Institut Mérieux, box D11, D11_8, 12_11/12/69.

73. Archives of the Institut Mérieux, box D11, D11_8, 16_22/01/70.

74. Archives of the Institut Mérieux, box D11, D11_10, 2_17/02/70.

75. Archives of the Institut Mérieux, box D11, D11_10, 3_17/03/70.

76. Gotschlich, Goldschneider and Artenstein, op. cit. (note 58).

77. Archives of the Institut Mérieux, box D11, D11_11, 1_09/04/70.

78. Archives of the Institut Mérieux, box D11, D11_11, 3_18/05/70.

79. Archives of the Institut Mérieux, box D11, D11_8, 8_04/12/69.

80. Archives of the Institut Mérieux, box D11, D11_8, 9_08/12/69.

81. Archives of the Institut Mérieux, box D11, D11_8, 11_10/12/69.

82. Archives of the Institut Mérieux, box D11, D11_8, 10_10/12/69.

83. Archives of the Institut Mérieux, op. cit. (note 81).

84. Archives of the Institut Mérieux, box D11, D11_8, 14_14/12/69.

85. Archives of the Institut Mérieux, box D11, D11_8, 19_29/01/70.

86. Archives of the Institut Mérieux, box D11, D11_8, 15_05/01/70.

87. Archives of the Institut Mérieux, box D11, D11_12, 2_19/06/70.

88. Archives of the Institut Mérieux, box D11, D11_12, 4_01/07/70.

89. Archives of the Institut Mérieux, box D11, D11_12, 8_27/07/70.

90. Archives of the Institut Mérieux, box D11, D11_12, 9_19/08/70.

91. Archives of the IMTSSA, box 2013 ZK 005-553, ‘Vaccination contre la Méningite Cérébro-spinale’ (1970), 1–8.

92. Archives of the Institut Mérieux, box D11, D11_13, 12_12/01/71.

93. Archives of the IMTSSA, box 2013 ZK 005-227, ‘Rapport sur la mission effectuée à Bougoula (République du Mali) par le Docteur Jean Étienne Médecin-Chef de la Sous-Section Méningite, Centre Muraz, Bobo-Dioulasso)’ (1971); Archives of the IMTSSA, box 2013 ZK 005-227, ‘Rapport sur l’enquête effectuée à Bobo-Dioulasso (Haute-Volta) concernant le vaccin antiméningococcique par le Docteur Jean Étienne Médecin-Chef de la Sous-Section Méningite, Centre Muraz, Bobo-Dioulasso’ (1971).

94. Archives of the IMTSSA, box 2013 ZK 005-640, ‘Immunogénicité et innocuité du vaccin antiméningococcique polysaccharidique A – Enquêtes de Bougoula (Mali) et Bobo-Dioulasso (Haute-Volta): Résultats finaux par le docteur Jean Étienne’ (1971).

95. Blume, op. cit. (note 15), 90–1.

96. Between 1963 and 1967, the Lapeyssonnie team of the IMTSSA provided the meningococcal strains that composed the whole cell meningococcal vaccine developed at that time by the Institut Mérieux.

97. Archives of the Institut Mérieux, box D11, D11_13, 14_12/01/71.

98. Archives of the WHO, box C11-181-14, ‘Grant to the Federal Ministry of Health, Lagos, Nigeria, in respect of controlled field trial of cerebrospinal meningitis vaccine’ (1971).

99. Sanborn, W.R., Bencić, Z., Cvjetanović, B., Gotschlich, Emil C., Pollock, Tom M. and Sippel, J.E., ‘Trial of a Serogroup A ¡eningococcus Polysaccharide Vaccine in Nigeria’, Progress in Immunological Standardization, 5 (1971), 497505.

100. Archives of the Institut Mérieux, box D11, D11_11, 3_18/05/70.

101. Archives of the Institut Mérieux, box D11, D11_12, 1_23/05/70.

102. Archives of the IMTSSA, box 2013 ZK 005-227, ‘XIIè Congrès International de Standardisation Biologique, 20 au 24 septembre 1971, Annecy-France – Rapport de mission par le docteur Jean Étienne Médecin-Chef de la Sous-Section Méningite, Centre Muraz, Bobo-Dioulasso’ (1971), 4.

103. Triau, René and Roumiantzeff, Micha, ‘La vaccination anti-méningococcique’, Médecine et Maladies Infectieuses, 14, 1 (1984), 8788.

104. Archives of the Institut Mérieux, box D11, D11_15, 1_18/05/71.

105. Archives of the Institut Mérieux, box D11, D11_15, 3_14/06/71.

106. Archives of the IMTSSA, op. cit. (note 102).

107. Archives of the WHO, box C11-181-16, ‘CTS Agreement with the High Institute of Public Health, Alexandria, in respect of field study of meningococcal-polysaccharide A vaccine’ (1972).

108. Wahdan, M.H., Rizk, F., El-Akkad, A.M., El Ghoroury, A.A., Hablas, R., Girgis, N.I., Amer, A., Boctar, W., Sippel, J.E., Gotschlich, Emil C., Triau, René, Sanborn, W.R. and Cvjetanović, B., ‘A Controlled Field Trial of a Serogroup A Meningococcal Polysaccharide Vaccine’, Bulletin of the World Health Organization, 48, 6 (1973), 667673.

109. Archives of the WHO, op. cit. (note 62).

110. Archives of the WHO, op. cit. (note 62).

111. Archives of the WHO, box C11-446-2SUD, ‘Grant of $1000 to the government of Sudan in relation with field study of meningococcal polysaccharide A vaccine’ (1974).

112. Archives of the IMTSSA, box 2013 ZK 005-549, ‘Letter to W.R. Sanborn from Léon Lapeyssonnie’, 8 February 1973.

113. Erwa, H.H., Haseeb, M.A., Idris, A.A., Lapeyssonnie, Léon, Sanborn, W.R. and Sippel, J.E., ‘A Serogroup A Meningococcal polysaccharide Vaccine: Studies in the Sudan to Combat Cerebrospinal Meningitis Caused by Neisseria meningitidis Group A’, Bulletin of the World Health Organization, 49, 3 (1973), 303304.

114. Archives of the IMTSSA, box 2013 ZK 005-538, ‘Table ronde sur l’immunoprophylaxie de la méningite cérébro-spinale – Le Mas d’Artigny 06570 Saint-Paul de Vence (France) – Vendredi 12 Octobre 1973’ (1973).

115. At that time, the CSMa was almost exclusively in Africa.

116. M. Machado, ‘L’épidémie de méningite cérébro-spinale au Brésil’, Médecine et Hygiène, 34 (1976), 483–5; Charles Mérieux, ‘Une aventure des temps modernes: la lutte contre l’épidémie de méningite au Brésil’, Informations Chimie, 157 (1976), 173–7.

117. A vaccine that uses a carrier protein to enhance the efficacy of the antigen.

118. Vipond, Caroline, Care, Rory and Feavers, Ian M., ‘History of Meningococcal Vaccines and their Serological Correlates of Protection’, Vaccine, 30 (2012), B11.

119. Tan, Lionel K.K., Carlone, Georges M. and Borrow, Ray, ‘Advances in the Development of Vaccines Against Neisseria meningitidis ’, The New England Journal of Medicine, 362, 16 (2010), 1512.

120. Graham, op. cit. (note 19), 422–3.

121. Blume, op. cit. (note 15), 30–3.

122. Vargha, Dora and Greene, Jeremy A., ‘Grey-Market Medicines: Diphtheria Antitoxin and the Decay of Biomedical Infrastructure’, The Lancet, 389, 10080 (2017), 1690.

123. Blume, op. cit. (note 15), 203.

124. Ibid., 106.

125. Global Polio Eradication Initiative (GPEI), http://polioeradication.org, accessed 5 May 2019.

126. Blume, op. cit. (note 15), 108.

I would like to thank the Institut Mérieux, the World Health Organization and the Service Historique de la Défense – Division Sud-Est – Toulon for providing access to their archives, and especially to Reynald Erard at the WHO for guidance and assistance. I would also like to thank Jonathan Simon and Gareth Millward for their invaluable help in preparing the manuscript, and the three anonymous Medical History reviewers for their comments.

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Vaccine Development and Collaborations: Lessons from the History of the Meningococcal A Vaccine (1969–73)

  • Baptiste Baylac-Paouly (a1) (a2)

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