Vaccines: the fourth century

Abstract

Vaccine development, which began with Edward Jenner's observations in the late 18th century, has entered its 4th century. From its beginnings, with the use of whole organisms that had been weakened or inactivated, to the modern-day use of genetic engineering, it has taken advantage of the tools discovered in other branches of microbiology. Numerous successful vaccines are in use, but the list of diseases for which vaccines do not exist is long. However, the multiplicity of strategies now available, discussed in this article, portends even more successful development of vaccines.

Figures

FIG. 1.

An outline of the history of live, attenuated vaccines. OPV, oral polio vaccine; ca, cold adapted.

FIG. 2.

An outline of the history of inactivated vaccines. IPV, inactivated polio; Vi, a capsular polysaccharide of typhoid bacillus; Pneumo, pneumococcus; Hep B, hepatitis B; Conj., conjugated; Hib, Haemophilus influenzae type B; mening, meningococcus.

FIG. 3.

The strategy used to develop a candidate dengue vaccine based on the yellow fever attenuated 17D strain as the vector. C, core; E, envelope. (Courtesy of Jean Lang, Sanofi Pasteur, reproduced with permission).

FIG. 4.

Induction of specific cytotoxic T lymphocytes against pp65 CMV matrix protein in volunteers given doses of a canarypox virus vector containing the gene for pp65 at 0, 3, and 6 months (arrows). Black triangles indicate previously seronegative volunteers, open circles previously seropositive volunteers, and open squares seronegative volunteers who received a placebo. Arrows signify vaccinations. (Reprinted from reference with permission of the publisher).

FIG. 5.

A diagram of the HPV virion showing the location of the L1 protein (A) and an electron micrograph of HPV16 VLPs composed of L1 made using yeast (B). (Reprinted from reference with permission of the publisher, copyright Elsevier [2008]).

FIG. 6.

Single-component RepliVax (single-round vaccine). The strategy of replicon formation based on flavivirus genomes by which single-cycle viruses are produced that can induce only noninfectious but immunogenic particles in the injected host is shown. C, core; E, envelope. (Reprinted from reference with permission of the publisher, copyright Elsevier [2009]).

FIG. 7.

Cationic lipid-based adjuvant formulated with measles Ha+F DNA Vaccine protects nonhuman primates. Neutralizing antibody responses in monkeys given measles virus hemagglutinogen and fusion genes in the form of DNA plasmids together with a cationic lipid-based adjuvant are shown. F, fusion; ID, intradermal; IM, intramuscular; PRNT, plaque reduction neutralization test. (Reprinted from reference with permission).

FIG. 8.

Percent cytotoxic T lymphocyte responses in volunteers given a vaccinia virus mutant (NYVAC) containing HIV clade C genes alone or preceded by priming with a DNA plasmid containing the same genes, showing the enhancement by the prime-boost strategy. ELISPOT, enzyme-linked immunospot. (Reprinted from reference [originally published in J. Exp. Med. doi:10.1084/jem.20071331] with permission of the publisher.)

FIG. 9.

Principle of transcutaneous immunization, in this case antigen and adjuvant delivery via a patch: a patch on the skin contains an influenza virus antigen and E. coli labile toxin as an adjuvant. The antigen migrates through the epidermis to reach the Langerhans cells, which carry it to the lymph nodes. (Reprinted from reference with permission of the publisher.)

FIG. 10.

BD Soluvia microneedle device for transcutaneous immunization. (Courtesy of Becton Dickinson, reproduced with permission).