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Dan M. Granoff (born January 22, 1944) is an infectious disease physician-scientist who was named the 2014 Maurice Hilleman/Merck Laureate by the American Society of Microbiology for outstanding contributions to vaccine discovery and development[1].  Beginning in 2011, Granoff held the Clorox Foundation Endowed Chair and was Director of the Center of Immunobiology and Vaccine Development at Children’s Hospital Oakland Research Institute (Currently University of California San Francisco (UCSF) Children’s Hospital Oakland).  He is the author or co-author of more than 225 research articles published in peer-reviewed journals, and his work has increased understanding of basic mechanisms of human immunity to encapsulated bacteria.  His work furthered development of vaccines against Haemophilus influenzae type b (Hib) and Neisseria meningitis (also called the meningococcus)[2][3].

Personal life

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Granoff was born in 1944 in New York City[4], NY. He divides his time between San Francisco, California, and Carmel Valley, California, with his partner, Marjory A Kaplan[5], a retired lawyer. He was married to Alice Baghdassarian Granoff, M.D., and divorced in 1985[6].  They have two sons Jonathan and Jeffrey Granoff.

Education

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Granoff completed his bachelors and medical degrees at Johns Hopkins University, Baltimore Maryland[7].  He completed Pediatric residency training at the Johns Hopkins Hospital, followed by a post-doctoral fellowship in Pediatric Infectious Diseases at Cleveland Metropolitan General Hospital (currently, MetroHealth Medical Center). 

Research    

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Development of Haemophilus influenzae type b (Hib) polysaccharide and polysaccharide-protein conjugate vaccines. 

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Community protection after vaccination (also referred to as "Herd immunity"

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With Drs. Trudy Murphy (then at Southwestern Medical School Dallas) and Michael Osterholm (then Minnesota Health Department) Granoff demonstrated how PRP-D (Hib capsular polysaccharide protein conjugate) vaccine decreased Hib disease in both vaccinated and unvaccinated children[8].

Effect of vaccination on asymptomatic Hib colonization of the nose and throat

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Granoff and his colleagues demonstrated an unexpected decrease in the presence of Hib in the noses and throats of healthy children who had been immunized with PRP-D compared to unvaccinated children and children vaccinated with an earlier vaccine containing unconjugated polysaccharide[9]. This finding provided the basis for the observed community protection associated with PRP-D vaccination.

Unexpected presence of mature B cells capable of responding to polysaccharide antigens in 2 month-old infants.

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In 1986 Granoff and his colleagues reported that a single injection of a modified Hib conjugate vaccine elicited a protective antibody response in two month-old infants[10]. Granoff’s findings proved that B cells, with the appropriate rearranged genes, were in fact present at age two months and were activated by a single injection of this Hib polysaccharide conjugate vaccine[11]. This result was unexpected since scientists at the time believed that two-month-olds did not have mature B cells capable of responding to polysaccharide antigens[12] [13].  

Defining the structure and function of human antibody to Hib polysaccharide.

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With Dr. Alexander H. Lucas, Granoff used idiotypic analysis to investigate variable region gene diversity in human antibodies for Hib polysaccharide[14]. They found dramatic changes in gene utilization by age of vaccination, and different Hib vaccine types. Collectively these studies contributed to making anti-Hib capsular antibodies one of the best understood human antibody systems at a molecular level[15]. 

A meningococcal serogroup A conjugate vaccine for Sub-Saharan Africa.  

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In 1999, Granoff and his colleagues at the World Health Organization, proposed the feasibility of developing and manufacturing a low cost, meningococcal vaccine for Africa using a public–private partnership[16][17]. As a result, in 2010, under the leadership of Dr. Marc LaForce, a low cost, vaccine, called MenAfriVac, was introduced in Sub-Saharan Africa. By the end of 2014, more than 150 million people had been immunized. The vaccine was shown to be highly effective in preventing group A epidemics. Critically, it decreased bacteria in the nose and throat, helping to establish herd immunity[18].

Discovery of the role of meningococcal Factor H binding protein in meningococcal pathogenesis.

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Collaborating with Sanjay Ram’s Laboratory, then at Boston University School of Medicine, Granoff and colleagues found that a meningococcal lipoprotein is critical for the ability of the bacteria to survive in human serum[19][20]. They renamed the liporprotein  “Factor H binding protein” or “FHbp”. FHbp is now the main or sole antigen in the two meningococcal serogroup B vaccines licensed in the U.S., Europe and in other areas of the world[21].

Improving efficacy of meningococcal serogroup B vaccines

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Low-FH binding mutants of FHbp

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In immunized humans the FHbp antigen forms a complex with human FH[22].  With Drs. Peter Beernink and Sanjay Ram, Granoff showed that FH binding to FHbp decreased protective antibody responses[23][24]. Beernink and Granoff went on to create mutant FHbp vaccines with amino acid substitutions that decreased FH binding, which elicited greater protective antibody responses[23][25]. They showed that, currently licensed FHbp-based meningococcal B vaccines can be improved by introducing these amino acid substitutions.

Meningococcal vaccines using native outer membrane vesicle (NOMV) 

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Granoff and his colleagues investigated over-expressing FHbp in NOMV prepared from mutant meningococcal strains[26].  The meningococcal NOMV vaccine combined with over-expressing mutant low FH-binding FHbp elicited much higher and broader protective antibody responses than control vaccines[27][28], including a currently licensed one. 

Publications

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Granoff authored or co-authored more than 225 research articles in peer-reviewed journals, review articles, and multiple textbook chapters including recent chapters on Meningococcal vaccines published in the 7th edition of Plotkin’s Vaccines[21], Granoff also co-edited a textbook on Hib vaccines with Dr. Ronald D Ellis[29].

Academic and Business career

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Granoff served as Director of the Division of Pediatric Infectious Diseases at Washington University School of Medicine and St. Louis Children’s Hospital from 1979 to 1993[4].  In 1993, he  became Executive Director of Clinical Vaccine Research at Chiron Corporation (Emeryville CA) with a joint appointment as a Scientist at Children’s Hospital Oakland Research Institute (Currently UCSF Benioff Children’s Hospital)]. His team at Chiron was responsible for clinical development of the first adjuvanted influenza vaccine[30], and a meningococcal serogroup C conjugate vaccine[31] used to control deadly outbreaks in the United Kingdom[32]. In 1995 Granoff became Vice President of Scientific Affairs. He left Chiron in 1998 to become a Senior Scientist at Children’s Hospital Oakland Research Institute[4].

Editorships

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Granoff served as Associate Editor of the journal, Pediatric Research (1982-1988)[33] and currently is a member of the Editorial Boards of Human Vaccines [34]and Immunotherapeutics and the journal Vaccine[35].  He also is on the Editorial Advisory Board of the journal, Clinical Infectious Diseases[36].

Recognition by scientific societies

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The American Society for Clinical Investigation (ASCI)

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Elected to membership in 1987[37].

The American Academy of Microbiology

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Elected as a Fellow in 2010[38].


The Infectious Diseases Society of America and the Pediatric Infectious Diseases Society

Elected as a Fellow to both organizations.

Awards

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1981 Alpha Omega Alpha

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Faculty honoree[39] at Washington University of Medicine, St. Louis

2010 Stanley A. Plotkin Awardee in Vaccinology[40], the Pediatric Infectious Diseases Society

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Granoff received this award for significant contributions to the field of “vaccinology.”

2014 Maurice Hilleman/Merck Laureate, the American Society of Microbiology

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Granoff received this award for outstanding contributions to vaccine discovery and development[1].

2017 Johns Hopkins School of Medicine Distinguished Medical Alumnus Award[41]

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Patents

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Granoff is inventor or co-inventor on multiple US and international patents including Patent Nos. US6,936,261; US8,968,748; US9,034,345; US9,439,957; US10,857,221; and US10,905,754 and others.

References

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  1. ^ a b "Past-ASM-Awardees-for-ASM-Awards" (PDF). https://asm.org/ASM/media/ASM-Branches/Past-ASM-Awardees-for-ASM-Awards-1-30-23.pdf. Retrieved 2023-02-11. {{cite web}}: External link in |website= (help)
  2. ^ Stephens, David S.; Greenwood, Brian; Brandtzaeg, Petter (2007-06-30). "Epidemic meningitis, meningococcaemia, and Neisseria meningitidis". Lancet (London, England). 369 (9580): 2196–2210. doi:10.1016/S0140-6736(07)61016-2. ISSN 1474-547X. PMID 17604802.
  3. ^ Soeters, Heidi M.; Blain, Amy; Pondo, Tracy; Doman, Brooke; Farley, Monica M.; Harrison, Lee H.; Lynfield, Ruth; Miller, Lisa; Petit, Susan; Reingold, Arthur; Schaffner, William; Thomas, Ann; Zansky, Shelley M.; Wang, Xin; Briere, Elizabeth C. (2018-08-31). "Current Epidemiology and Trends in Invasive Haemophilus influenzae Disease-United States, 2009-2015". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 67 (6): 881–889. doi:10.1093/cid/ciy187. ISSN 1537-6591. PMC 6181225. PMID 29509834.
  4. ^ a b c Granoff, Dan M. (2013-05). "Portrait: coincidences, convergences and opportunities". Human Vaccines & Immunotherapeutics. 9 (5): 945–949. doi:10.4161/hv.25151. ISSN 2164-554X. PMC 3899160. PMID 23807081. {{cite journal}}: Check date values in: |date= (help)
  5. ^ Attorneys, All California. "Marjory Ann Kaplan". All California Attorneys. Retrieved 2023-02-11.
  6. ^ "Alice Granoff Obituary - Tucson, AZ". Dignity Memorial. Retrieved 2023-02-11.
  7. ^ "CHORI's Dan M. Granoff Awarded Prestigious Alumni Award from the Johns Hopkins University, School of Medicine". www.newswise.com. Retrieved 2023-02-11.
  8. ^ Murphy TV, White KE, Pastor P, Gabriel L, Medley F, Granoff DM, Osterholm MT. (1993). "Decreased Haemophilus Colonization in Children Vaccinated with Haemophilus Influenzae Type B Conjugate Vaccine". Journal of Pediatrics. 122 (4): 517–23.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ^ Murphy, Trudy V.; White, Karen E.; Pastor, Patricia; Gabriel, Linda; Medley, Francinne; Granoff, Dan M.; Osterholm, Michael T. (1993-01-13). "Declining Incidence of Haemophilus influenzae Type b Disease Since Introduction of Vaccination". JAMA. 269 (2): 246–248. doi:10.1001/jama.1993.03500020080036. ISSN 0098-7484.
  10. ^ Einhorn, M. S.; Weinberg, G. A.; Anderson, E. L.; Granoff, P. D.; Granoff, D. M. (1986-08-09). "Immunogenicity in infants of Haemophilus influenzae type B polysaccharide in a conjugate vaccine with Neisseria meningitidis outer-membrane protein". Lancet (London, England). 2 (8502): 299–302. doi:10.1016/s0140-6736(86)90001-2. ISSN 0140-6736. PMID 2874327.
  11. ^ Lucas AH, Azimi FH, Mink CM, Granoff DM (1993). "Age-dependent V region expression in the human antibody response to the Haemophilus influenzae type b polysaccharide". Journal of Immunology. 150 (5): 2050–2056.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  12. ^ Haemophilus influenzae : epidemiology, immunology, and prevention of disease. Sarah H. Sell, Peter F. Wright, Vanderbilt University, Tennessee. Department of Public Health. New York: Elsevier Biomedical. 1982. pp. 129–134. ISBN 0-444-00683-4. OCLC 8431344.{{cite book}}: CS1 maint: others (link)
  13. ^ Haemophilus influenzae : epidemiology, immunology, and prevention of disease. Sarah H. Sell, Peter F. Wright, Vanderbilt University, Tennessee. Department of Public Health. New York: Elsevier Biomedical. 1982. pp. 121–127. ISBN 0-444-00683-4. OCLC 8431344.{{cite book}}: CS1 maint: others (link)
  14. ^ Lucas, Alexander H; McLean, Gary R; Reason, Donald C; O’Connor, Adam P; Felton, Mistique C; Moulton, Karen D (2003-08-01). "Molecular ontogeny of the human antibody repertoire to the Haemophilus influenzae type b polysaccharide: expression of canonical variable regions and their variants in vaccinated infants". Clinical Immunology. 108 (2): 119–127. doi:10.1016/S1521-6616(03)00094-9. ISSN 1521-6616.
  15. ^ Reason, D. C.; O'Connor, A. P.; Lucas, A. H. (2001). "Structural determinants of the human idiotype HibId-1". Journal of molecular recognition: JMR. 14 (6): 393–400. doi:10.1002/jmr.548. ISSN 0952-3499. PMID 11757072.
  16. ^ Jódar, Luis; LaForce, F. Marc; Ceccarini, Costante; Aguado, Teresa; Granoff, Dan M. (2003-05-31). "Meningococcal conjugate vaccine for Africa: a model for development of new vaccines for the poorest countries". The Lancet. 361 (9372): 1902–1904. doi:10.1016/S0140-6736(03)13494-0. ISSN 0140-6736. PMID 12788589.
  17. ^ Aguado, M. Teresa; Jodar, Luis; Granoff, Dan; Rabinovich, Regina; Ceccarini, Costante; Perkin, Gordon W. (2015-11-15). "From Epidemic Meningitis Vaccines for Africa to the Meningitis Vaccine Project". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 61 Suppl 5 (Suppl 5): S391–395. doi:10.1093/cid/civ593. ISSN 1537-6591. PMC 4639495. PMID 26553665.
  18. ^ Diomandé, Fabien V. K.; Djingarey, Mamoudou H.; Daugla, Doumagoum M.; Novak, Ryan T.; Kristiansen, Paul A.; Collard, Jean-Marc; Gamougam, Kadidja; Kandolo, Denis; Mbakuliyemo, Nehemie; Mayer, Leonard; Stuart, James; Clark, Thomas; Tevi-Benissan, Carol; Perea, William A.; Preziosi, Marie-Pierre (2015-11-15). "Public Health Impact After the Introduction of PsA-TT: The First 4 Years". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 61 Suppl 5 (Suppl 5): S467–472. doi:10.1093/cid/civ499. ISSN 1537-6591. PMC 4639484. PMID 26553676.
  19. ^ Madico, Guillermo; Welsch, Jo Anne; Lewis, Lisa A.; McNaughton, Anne; Perlman, David H.; Costello, Catherine E.; Ngampasutadol, Jutamas; Vogel, Ulrich; Granoff, Dan M.; Ram, Sanjay (2006-07-01). "The meningococcal vaccine candidate GNA1870 binds the complement regulatory protein factor H and enhances serum resistance". Journal of Immunology (Baltimore, Md.: 1950). 177 (1): 501–510. doi:10.4049/jimmunol.177.1.501. ISSN 0022-1767. PMC 2248442. PMID 16785547.
  20. ^ Granoff, Dan M.; Welsch, Jo Anne; Ram, Sanjay (2009-02). "Binding of complement factor H (fH) to Neisseria meningitidis is specific for human fH and inhibits complement activation by rat and rabbit sera". Infection and Immunity. 77 (2): 764–769. doi:10.1128/IAI.01191-08. ISSN 1098-5522. PMC 2632036. PMID 19047406. {{cite journal}}: Check date values in: |date= (help)
  21. ^ a b Plotkin's vaccines. Stanley A. Plotkin, Walter A. Orenstein, Paul A. Offit (Seventh edition ed.). Philadelphia, PA. 2018. pp. 644–662. ISBN 978-0-323-39302-7. OCLC 989157433. {{cite book}}: |edition= has extra text (help)CS1 maint: location missing publisher (link) CS1 maint: others (link)
  22. ^ Granoff, Dan M. (2014-08-01). "Improving Safety and Efficacy of Meningococcal Vaccines: Vaccines based on a relatively sparse surface lipoprotein extend coverage to serogroup B; amino acid changes could lead to further enhancements". Microbe Magazine. 9 (8): 321–327. doi:10.1128/microbe.9.321.1. ISSN 1558-7452.
  23. ^ a b Beernink, Peter T.; Shaughnessy, Jutamas; Braga, Emily M.; Liu, Qin; Rice, Peter A.; Ram, Sanjay; Granoff, Dan M. (2011-03-15). "A meningococcal factor H binding protein mutant that eliminates factor H binding enhances protective antibody responses to vaccination". Journal of Immunology (Baltimore, Md.: 1950). 186 (6): 3606–3614. doi:10.4049/jimmunol.1003470. ISSN 1550-6606. PMC 3098282. PMID 21325619.
  24. ^ Granoff, Dan M.; Costa, Isabella; Konar, Monica; Giuntini, Serena; Van Rompay, Koen K. A.; Beernink, Peter T. (2015-09-01). "Binding of Complement Factor H (FH) Decreases Protective Anti-FH Binding Protein Antibody Responses of Infant Rhesus Macaques Immunized With a Meningococcal Serogroup B Vaccine". The Journal of Infectious Diseases. 212 (5): 784–792. doi:10.1093/infdis/jiv081. ISSN 1537-6613. PMC 4539902. PMID 25676468.
  25. ^ Granoff, Dan M.; Giuntini, Serena; Gowans, Flor A.; Lujan, Eduardo; Sharkey, Kelsey; Beernink, Peter T. (2016-09-08). "Enhanced protective antibody to a mutant meningococcal factor H-binding protein with low-factor H binding". JCI insight. 1 (14): e88907. doi:10.1172/jci.insight.88907. ISSN 2379-3708. PMC 5033880. PMID 27668287.
  26. ^ Hou, Victor C.; Koeberling, Oliver; Welsch, Jo Anne; Granoff, Dan M. (2005-08-15). "Protective Antibody Responses Elicited by a Meningococcal Outer Membrane Vesicle Vaccine with Overexpressed Genome‐Derived Neisserial Antigen 1870". The Journal of Infectious Diseases. 192 (4): 580–590. doi:10.1086/432102. ISSN 0022-1899. {{cite journal}}: no-break space character in |first3= at position 3 (help); no-break space character in |first4= at position 4 (help); no-break space character in |first= at position 7 (help)
  27. ^ Beernink, Peter T.; Shaughnessy, Jutamas; Pajon, Rolando; Braga, Emily M.; Ram, Sanjay; Granoff, Dan M. (2012-05-10). "The Effect of Human Factor H on Immunogenicity of Meningococcal Native Outer Membrane Vesicle Vaccines with Over-Expressed Factor H Binding Protein". PLOS Pathogens. 8 (5): e1002688. doi:10.1371/journal.ppat.1002688. ISSN 1553-7374. PMC 3349754. PMID 22589720.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  28. ^ Beernink, Peter T.; Vianzon, Vianca; Lewis, Lisa A.; Moe, Gregory R.; Granoff, Dan M. (2019-06-25). Pirofski, Liise-anne (ed.). "A Meningococcal Outer Membrane Vesicle Vaccine with Overexpressed Mutant FHbp Elicits Higher Protective Antibody Responses in Infant Rhesus Macaques than a Licensed Serogroup B Vaccine". mBio. 10 (3). Stephen Pelton, Ian Feavers: e01231–19. doi:10.1128/mBio.01231-19. ISSN 2161-2129. PMC 6581866. PMID 31213564.{{cite journal}}: CS1 maint: PMC format (link)
  29. ^ Development and clinical uses of haemophilus b conjugate vaccines. Ronald W. Ellis, Dan M. Granoff. New York: M. Dekker. 1994. ISBN 0-8247-9186-X. OCLC 29848230.{{cite book}}: CS1 maint: others (link)
  30. ^ De Donato, S.; Granoff, D.; Minutello, M.; Lecchi, G.; Faccini, M.; Agnello, M.; Senatore, F.; Verweij, P.; Fritzell, B.; Podda, A. (1999-08-06). "Safety and immunogenicity of MF59-adjuvanted influenza vaccine in the elderly". Vaccine. 17 (23–24): 3094–3101. doi:10.1016/s0264-410x(99)00138-3. ISSN 0264-410X. PMID 10462245.
  31. ^ Jones, D. H. (2001-01). "Menjugate (Chiron)". Current Opinion in Investigational Drugs (London, England: 2000). 2 (1): 47–49. ISSN 1472-4472. PMID 11527011. {{cite journal}}: Check date values in: |date= (help)
  32. ^ Miller, E.; Salisbury, D.; Ramsay, M. (2001-10-15). "Planning, registration, and implementation of an immunisation campaign against meningococcal serogroup C disease in the UK: a success story". Vaccine. 20 Suppl 1: S58–67. doi:10.1016/s0264-410x(01)00299-7. ISSN 0264-410X. PMID 11587814.
  33. ^ "Pediatric Research". Nature. Retrieved 2023-03-21.
  34. ^ "Human Vaccines & Immunotherapeutics". Taylor & Francis. Retrieved 2023-03-21.
  35. ^ "Editorial Board - Vaccine - Journal - Elsevier". www.journals.elsevier.com. Retrieved 2023-02-11.
  36. ^ academic.oup.com https://academic.oup.com/cid/pages/Editorial_Board. Retrieved 2023-02-11. {{cite web}}: Missing or empty |title= (help)
  37. ^ "The American Society for Clinical Investigation". Retrieved 2023-02-11.
  38. ^ "Search - ASM Academy Fellow Directory". myasm.asm.org. Retrieved 2023-02-12.
  39. ^ "Member Search". Alpha Omega Alpha. Retrieved 2023-03-21.
  40. ^ Foundation, PIDS. "Stanley A. Plotkin Award – PIDS Foundation". pidsfoundation.org. Retrieved 2023-02-11.
  41. ^ Office, SoM Development and Alumni Relations. "Past Alumni Award Winners". www.hopkinsmedicine.org. Retrieved 2023-02-11.
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