eBriefing

A Shot at Survival: Progress and Challenges in New and Emerging Vaccines

A Shot at Survival
Reported by
Marilynn Larkin

Posted February 29, 2008

Overview

At a December 13, 2007, symposium at the Academy, five speakers shared the successes and challenges of developing and deploying novel vaccines. Roger Glass of the National Institutes of Health emphasized that while we have a rotavirus vaccine that works in developed countries, its efficacy in the developing world—where it's needed most—has yet to be proven. The American Cancer Society's Debbie Saslow provided insights into the ubiquity of human papillomavirus (HPV), the infection that causes cervical cancer.

Keith Klugman of Emory University tackled pneumococcal infection, first exploring the links between pneumococcus and pneumonia, and then making the case—admittedly controversial—for a synergism between pneumococcal infection and the influenza virus that could lead to severe clinical consequences. Christopher Plowe summarized the challenges of a malaria vaccine, highlighting the size of the malaria falciparum parasite and its effective use of antigenic variation to elude the immune system as key obstacles.


Sponsorship

This conference and eBriefing were made possible with support from:

     

Web Sites

CDC-Influenza | Information for Health Care Professionals
Contains links to pages that offer public health and healthcare professionals key information about vaccination, infection control, prevention, treatment, and diagnosis of seasonal influenza.

Global Alliance for Vaccines and Immunizations (GAVI)
The GAVI Alliance is a unique, multi-dimensional partnership of public and private sector resources with a single, shared focus: to improve child health in the poorest countries by extending the reach and quality of immunization coverage within strengthened health services.

HPV, Cervical Cancer, and the New Vaccine
The Henry Kaiser Family Foundation put together this instructional module about the new HPV vaccine, including this policy fact sheet.

Medicines for Malaria Venture
A nonprofit organization created to discover, develop and deliver new antimalarial drugs through effective public-private partnerships.

National Institute of Allergy and Infectious Diseases (NIH)
NIAID sponsors research on malaria, provides resources for researchers, lists partners, and releases reports and summaries of their activities.

PATH Malaria Vaccine Initiative
The PATH Malaria Vaccine Initiative is a focused vaccine development program created in 1999 through a grant from the Bill & Melinda Gates Foundation.

Rotavirus Homepage — CDC
This homepage at the Centers for Disease Control and Prevention (CDC) has links to information about rotavirus, global and national surveillance, vaccination and intussusception.

Streptococcus pneumoniae Disease
The U.S. CDC has information about Streptococcus pneumoniae and vaccines.

U.S. FDA Product Approval — Information on HPV Vaccine
This site contains information on the clinical review of the vaccine along with basic facts about HPV.


Journal Articles

Roger Glass

Fischer TK, Viboud C, Parashar U, et al. 2007. Hospitalizations and deaths from diarrhea and rotavirus among children <5 years of age in the United States, 1993-2003. J. Infect. Dis. 195: 1117-1125.

Glass RI. 2007. New hope for defeating rotavirus. Sci. Am. 294: 46-55.

Glass RI, Bresee JD, Turcios, et al. 2005. Rotavirus vaccines: targeting the developing world. J. Infect. Dis. 192: S160-S166. Full Text

Glass RI, Parashar UD, Bresee JD, et al. 2006. Rotavirus vaccines: current prospects and future challenges. Lancet 368: 323-332.

Parashar UD, Alexander JP, Glass RI, et al. 2006. Prevention of rotavirus gastroenteritis among infants and children. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm. Rep. 55(RR-12):1-13. Full Text

Patel MM, Tate JE, Selvarangan R, et al. 2007. Rotavirus infection alters peripheral T-cell homeostasis in children with acute diarrhea. J. Virol. 81: 3904-3912. Full Text

Widdowson MA, Meltzer MI, Zhang X, et al. 2007. Cost-effectiveness and potential impact of rotavirus vaccination in the United States. Pediatrics 119: 684-697.

Debbie Saslow

Franco EL, Schlecht NF, Saslow D. 2003. The epidemiology of cervical cancer. Cancer J. 9: 348-359. Review.

Mahoney MC, Saslow D, Cohen CJ; ACS. 2003. ACS guideline for the early detection of cervical cancer. Am. Fam. Physician 67: 1677-1678, 1680. Full Text

Garcia FA, Saslow D. 2007. Prophylactic human papillomavirus vaccination: a breakthrough in primary cervical cancer prevention. Obstet. Gynecol. Clin. North Am. 34: 761-781.

Saslow D, Castle PE, Cox JT; Gynecologic Cancer Advisory Group, et al. 2007. American Cancer Society Guideline for human papillomavirus (HPV) vaccine use to prevent cervical cancer and its precursors. CA Cancer J. Clin. 57: 7-28. Review. Full Text

Saslow D, Runowicz CD, Solomon D, et al. 2003. American Cancer Society guideline for the early detection of cervical neoplasia and cancer. J. Low. Genit. Tract Dis. 7: 67-86.

Saslow D, Wheeler CM. 2007. Human papillomavirus vaccines: who will pay, who will receive, when to administer? Ethn. Dis. 17(2 Suppl 2): S2-8-13.

Wright TC Jr, Schiffman M, Solomon D, et al. 2004. Interim guidance for the use of human papillomavirus DNA testing as an adjunct to cervical cytology for screening. Obstet. Gynecol. 103: 304-309. Review.

Keith Klugman

Alanee SR, McGee L, Jackson D, et al. 2007. Association of serotypes of Streptococcus pneumoniae with disease severity and outcome in adults: an international study. Clin. Infect. Dis. 45: 46-51.

Albrich WC, Madhi SA, Lafond KE, Klugman KP. 2007. Herd immunity after pneumococcal conjugate vaccination. Lancet 370: 218-219.

Anderson R, Steel HC, Cockeran R, et al. 2007. Clarithromycin alone and in combination with ceftriaxone inhibits the production of pneumolysin by both macrolide-susceptible and macrolide-resistant strains of Streptococcus pneumoniae. J. Antimicrob. Chemother. 59: 224-229.

Anderson R, Steel HC, Cockeran R, et al. 2007. Comparison of the effects of macrolides, amoxicillin, ceftriaxone, doxycycline, tobramycin and fluoroquinolones, on the production of pneumolysin by Streptococcus pneumoniae in vitro. J. Antimicrob. Chemother. 60: 1155-1158.

Farrell DJ, Klugman KP, Pichichero M. 2007. Increased antimicrobial resistance among nonvaccine serotypes of Streptococcus pneumoniae in the pediatric population after the introduction of 7-valent pneumococcal vaccine in the United States. Pediatr. Infect. Dis J. 26: 123-128.

Klugman KP. 2007. Clinical impact of antibiotic resistance in respiratory tract infections. Int. J. Antimicrob. Agents Feb; 29 Suppl 1: S6-10.

Klugman KP, Madhi SA. 2007. Pneumococcal vaccines and flu preparedness. Science 316: 49-50.

Klugman KP, McGee L. 2007. Resurgence of the multiresistant pneumococcus in the United States: a commentary. Pediatr. Infect. Dis. J. 26: 473-474.

Madhi SA, Adrian P, Kuwanda L, et al. 2007. Long-term effect of pneumococcal conjugate vaccine on nasopharyngeal colonization by Streptococcus pneumoniae—and associated interactions with Staphylococcus aureus and Haemophilus influenzae colonization—in HIV-Infected and HIV-uninfected children. J. Infect. Dis. 196: 1662-1666.

Siber GR, Chang I, Baker S, et al. 2007. Estimating the protective concentration of anti-pneumococcal capsular polysaccharide antibodies. Vaccine 25: 3816-3826.

Christopher Plowe

Arman M, Raza A, Tempest LJ, et al. 2007. Platelet-mediated clumping of Plasmodium falciparum infected erythrocytes is associated with high parasitemia but not severe clinical manifestations of malaria in African children. Am. J. Trop. Med. Hyg. 77: 943-946.

Barnes KI, Lindegardh N, Ogundahunsi O, et al. 2007. World Antimalarial Resistance Network (WARN) IV: clinical pharmacology. Malar. J. 6:122. Full Text

Nyunt MM, Plowe CV. 2007. Pharmacologic advances in the global control and treatment of malaria: combination therapy and resistance. Clin. Pharmacol. Ther. 82: 601-605.

Plowe CV, Roper C, Barnwell JW, et al. 2007. World Antimalarial Resistance Network (WARN) III: molecular markers for drug resistant malaria. Malar. J. 6: 121. Full Text

Price RN, Dorsey G, Ashley EA, et al. 2007. World Antimalarial Resistance Network I: clinical efficacy of antimalarial drugs. Malar. J. 6:119. Full Text

Rowe JA, Handel IG, Thera MA, et al. 2007. Blood group O protects against severe Plasmodium falciparum malaria through the mechanism of reduced rosetting. Proc. Natl. Acad. Sci. USA 104: 17471-17476. Full Text

Sibley CH, Barnes KI, Plowe CV. 2007. The rationale and plan for creating a World Antimalarial Resistance Network (WARN). Malar. J. 6: 118. Full Text

Sibley CH, Barnes KI, Watkins WM, Plowe CV. 2008. A network to monitor antimalarial drug resistance: a plan for moving forward. Trends Parasitol. 24: 43-48.

Takala SL, Coulibaly D, Thera MA, et al. 2007. Dynamics of polymorphism in a malaria vaccine antigen at a vaccine-testing site in Mali. PLoS Med. 4: e93. Full Text

Takala SL, Smith DL, Thera MA, et al. 2007. Short report: rare Plasmodium falciparum merozoite surface protein 1 19-kda (msp-1(19)) haplotypes identified in Mali using high-throughput genotyping methods. Am. J. Trop. Med. Hyg. 76: 855-859.

Thera MA, Doumbo OK, Coulibaly D, et al. 2006. Safety and allele-specific immunogenicity of a malaria vaccine in Malian adults: results of a phase I randomized trial. PLoS Clin. Trials 1: e34. Full Text Free in PMC

Rino Rappuoli

Barocchi MA, Censini S, Rappuoli R. 2007. Vaccines in the era of genomics: the pneumococcal challenge. Vaccine 25: 2963-2973.

Del Giudice G, Fragapane E, Bugarini R, et al. 2006. Vaccines with the MF59 adjuvant do not stimulate antibody responses against squalene. Clin. Vaccine Immunol. 13: 1010-1013. Full Text

Johri AK, Paoletti LC, Glaser P, et al. 2006. Group B Streptococcus: global incidence and vaccine development. Nat. Rev. Microbiol. 4: 932-942.

Muzzi A, Masignani V, Rappuoli R. 2007. The pan-genome: towards a knowledge-based discovery of novel targets for vaccines and antibacterials. Drug Discov. Today 12: 429-439.

Rappuoli R. 2007. Bridging the knowledge gaps in vaccine design. Nat. Biotechnol. 25: 1361-1366.

Rappuoli R. 2007. An audience with... Rino Rappuoli. Nat. Rev. Drug Discov. 6: 694.

Rappuoli R, Ulmer J. 2007. Vaccines research and development: poised for rapid growth. Curr. Opin. Biotechnol. Dec 5; [Epub ahead of print]

Samdal HH, Bakke H, Oftung F, et al. 2005. A non-living nasal influenza vaccine can induce major humoral and cellular immune responses in humans without the need for adjuvants. Hum. Vaccin. 1: 85-90. (PDF, 369 KB) Full Text

Ulmer JB, Valley U, Rappuoli R. 2006. Vaccine manufacturing: challenges and solutions. Nat. Biotechnol. 24: 1377-1383.

Speakers

Roger Glass, MD, PhD

National Institutes of Health
e-mail | web site | publications

Roger Glass is director of the Fogarty International Center at NIH and the associate director of NIH for International Research. He completed his undergraduate, medical, and public health studies at Harvard and spent many years at CDC as chief of the Viral Gastroenteritis Unit. His research interests were initiated by spending four years in Bangladesh working on the control and prevention of diarrheal diseases, a main cause of death among children in the developing world.

Since then, he has continued to seek new ways to prevent diarrheal diseases through the use of vaccines. His work has led him to train and collaborate with scientists from more 60 countries and under his leadership, his group has published more than 500 scientific papers on the diagnosis, control, and prevention of diarrheal diseases. Glass is a member of the Institute of Medicine of the National Academies of Science and has received the Lifetime Achievement Award from the Centers for Disease Control and Prevention.

Debbie Saslow, PhD

American Cancer Society
e-mail | web site | publications

Debbie Saslow is the director of breast and gynecologic cancer in the Department of Cancer Control Science at the American Cancer Society's National Home Office in Atlanta. Saslow is responsible for the scientific content of the Society's breast and gynecologic cancer policies, materials, programs, and communications. Saslow manages the review and update of the Society's guidelines for the early detection of both breast and cervical cancers, and recently led the development of ACS guidelines and position statements for the HPV vaccine. She has been instrumental in building collaborative relationships with organizations across the public, private, and not-for-profit sectors.

Before joining the American Cancer Society, Saslow was coordinator of the President's National Action Plan on Breast Cancer (1994–1997). She is a frequent lecturer on cancer screening, genetic testing, cancer epidemiology, disparities, HPV and HPV vaccines. She is an author on more than 30 articles in peer-reviewed journals, and completed a postdoctoral fellowship at the National Cancer Institutes' Laboratory of Pathology in Women's Cancers. She received her undergraduate degree in biology with honors from Brown University, and her PhD in human and molecular genetics from Yale University.

Keith Klugman, MD, PhD

Emory University
e-mail | web site | publications

Keith Klugman is the William H. Foege Chair of Global Health in the Hubert Department of Global Health at the Rollins School of Public Health, Emory University, in Atlanta, GA, USA. He is also a professor of Medicine in the Division of Infectious Diseases of the School of Medicine at that university and a visiting researcher in the Respiratory Diseases Branch of the Centers for Disease Control and Prevention (CDC). He is the co-director of the Respiratory and Meningeal Pathogens Research Unit of the University of the Witwatersrand, the Medical Research Council and the National Institute for Communicable Diseases in Johannesburg, South Africa.

Klugman is a member of the executive committee of the International Society of Infectious Diseases and chair of the International Committee of the American Society for Microbiology, the largest single life science society, with over 42,000 members worldwide. The umbella organization of all national microbiology societies is the International Union of Microbiological Societies, of which Klugman is currently vice chair. He has chaired expert committees for the World Health Organization in Geneva and the Wellcome Trust in London. He serves as an editor or member of the editorial board of eight international journals on medicine, infectious diseases, and antimicrobials.

Klugman's research interests are in antibiotics, antimicrobial resistance, and vaccines for bacterial pathogens—particularly the pneumococcus. He has published more than 350 papers on these subjects to date.

Christopher Plowe, MD, MPH

University of Maryland
e-mail | web site | publications

Christopher Plowe is a physician and malariologist who leads a multidisciplinary clinical translational malaria research team at the University of Maryland's Center for Vaccine Development, with field sites in Malawi, Central Africa, and in Mali, West Africa. He is presently leading malaria vaccine trials in Mali, but he is best known for his work on the molecular epidemiology of drug resistant malaria. Working with African colleagues, his group at the University of Maryland developed rapid molecular assays to detect drug resistant malaria and used these tests to understand the population genetics of malaria and to control malaria outbreaks and inform treatment policy decisions.

Plowe has degrees in philosophy and medicine from Cornell University and in public health from Columbia University, and did fellowships in malaria research at the National Institutes of Health and in infectious diseases at Johns Hopkins University before joining the faculty of the University of Maryland School of Medicine, where he is a professor of Medicine and Doris Duke Distinguished Clinical Scientist. In 2007, Plowe was selected as a Howard Hughes Medical Institute Investigator in patient-oriented research.

Rino Rappuoli, PhD

Novartis Vaccines & Diagnostics
e-mail | web site | publications

Rino Rappuoli is global head of vaccines research at Novartis Vaccines & Diagnostics and is based in Siena, Italy. Previously he was head of R&D at Sclavo (Italy), and then head of Vaccine Research and CSO at Chiron Corporation.

His team developed the first recombinant bacterial vaccine (against pertussis), the first conjugate vaccine against meningococcus, and an experimental vaccine against Helicobacter pylori. Recently, his team was the first to use the power of genomics to develop new vaccines (reverse vaccinology) and used it to develop a vaccine against group B meningococcus. Among their present activities are the development of influenza vaccines produced in cell culture and the development of vaccines against avian influenza.

Among Rappuoli's scientific contributions, he was cofounder of the field of cellular microbiology, a discipline that has merged cell biology and microbiology. He is a member of the U.S. National Academy of Sciences (NAS) and of the European Molecular Biology Organization (EMBO).


Marilynn Larkin

Marilynn Larkin is a medical editor, journalist, and videographer based in New York City. Her work has frequently appeared in, among others, The Lancet, The Lancet Infectious Diseases, and Reuters Health's professional newswire. She has served as editor of many clinical publications and is author of five medical books for general readers as well as Reporting on Health Risk, a handbook for journalists. She is currently head of publications for The Society for Biomolecular Screening.