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Review
. 2013 Feb 7;368(6):551-60.
doi: 10.1056/NEJMra1204186.

Designing tomorrow's vaccines

Gary J Nabel  1
Affiliations
Review

Designing tomorrow's vaccines

Gary J Nabel. N Engl J Med. .
No abstract available

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Figures

Figure 1
Figure 1. Timelines for Vaccine Development and Licensure of Commercial Vaccines
Panel A shows major milestones and advances in vaccine development and the cumulative number of licensed vaccines since the time of Edward Jenner’s first use of a vaccination against smallpox in 1796. Panel B shows the timeline for licensure of commercial vaccines against the indicated pathogens. The abbreviation mAb denotes monoclonal antibody, OspA outer surface protein A, rBS recombinant B subunit of cholera toxin, rDNA recombinant DNA, and WC whole-cell Vibrio cholerae O1.
Figure 2
Figure 2. Structure of Viral or Bacterial Glycoproteins and Their Role in Host Invasion
A detailed knowledge of the mechanism by which viral glycoproteins mediate entry into host cells can now be applied to pathogens that once were not susceptible to vaccines, including human immunodeficiency virus (HIV) (Panel A, Protein Data Bank code 3JWD), influenza virus (Panel B, Protein Data Bank code 1RU7), and meningococcus (Panel C, adapted with permission from Scarselli et al.; Protein Data Bank code 2Y7S).– MPER denotes membrane proximal external region, and V1V2 variable regions 1 and 2. The Protein Data Bank is accessible at www.pdb.org.
Figure 3
Figure 3. Molecular Evolution of a Successful Broadly Neutralizing Antibody
Deep sequencing (i.e., the ability to generate millions of independent sequences of a gene product) identifies critical intermediates for the evolution of broadly neutralizing antibodies and guides vaccine development. In Panel A, maximum-likelihood trees of heavy-chain sequences were derived from the IGHV1-2 gene that gives rise to a broadly neutralizing antibody, VRC01, in a representative patient, donor 74, as described previously. The donor 74 tree is rooted in the putative reverted unmutated ancestor of the heavy chain of a specific broadly neutralizing CD4-binding site monoclonal antibody, VRC-PG04 (as shown in Panel B, Protein Data Bank code 3SE9). Sequences from other donors are included in the cross-donor phylogenetic analysis. Bars representing 0.1 changes per nucleotide site are shown. Sequences within the shaded box include autologous VRC01-like heavy-chain sequences that neutralize HIV with good potency and breadth and are probably clonal relatives of VRC-PG04. Sequences highlighted in blue and purple represent broadly neutralizing antibodies isolated with structural probes.
Figure 4
Figure 4. The Spectrum of Costimulation from Adjuvants to Viruses
A cellular and molecular understanding of dendritic-cell biology has facilitated improvements in vaccine-induced immune responses. Rather than generating responses through infection, immune stimulation can be achieved by increasingly complex modes of antigen presentation that range from introduction of selected proteins, with or without adjuvants, to gene-delivered immunogens, viruslike particles (VLP), structured arrays, or attenuated viruses. These approaches represent a spectrum of complexity and mimicry that elicits protective immunity without inflicting the adverse consequences of natural infection. HBV denotes hepatitis B virus, HPV human papillomavirus, VEE Venezuelan equine encephalitis, and WT wild type.
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References

    1. Landry S, Heilman C. Future directions in vaccines: the payoffs of basic research. Health Aff (Millwood) 2005;24:758–69. - PubMed
    1. Berkley S. Getting the miracle of vaccines to those who most need them. Presented at the John Ring LaMontagne Memorial Lecture; May 22, 2012; Bethesda, MD: National Institutes of Health; ( http://videocast.nih.gov/summary.asp?live=11173)
    1. Impact of vaccines universally recommended for children — United States, 1900–1998. MMWR Morb Mortal Wkly Rep. 1999;48:243–8. - PubMed
    1. Roush SW, Murphy TV. Historical comparisons of morbidity and mortality for vaccine-preventable diseases in the United States. JAMA. 2007;298:2155–63. - PubMed
    1. World malaria report 2011: fact sheet. Geneva: World Health Organization; ( http://www.who.int/malaria/world_malaria_report_2011/WMR2011_factsheet.pdf)

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