Building on the success of the Expanded Programme on Immunization: enhancing the focus on disease prevention and control.

The Expanded Programme on Immunization (EPI) has succeeded in establishing a vaccine delivery system in all low and middle income (LMI) countries. Because EPI has focused on immunization delivery, its major outcome is measured in many countries only as vaccine coverage, not as disease reduction, the real goal of EPI. Monitoring disease reduction requires real-time case-based disease surveillance and appropriate interventions, for which a functional public health infrastructure is needed. If the highest priority for assessing impact of EPI shifts to disease prevention and control from vaccine coverage, the programme may be transformed to one of control of childhood communicable diseases (CCCD), with the potential of expanding the range of diseases of children and adults for control and of integrating all other current vertical (single disease) control efforts with it. EPI provides the essential platform on which CCCD can be built to create a public health infrastructure.

WITHDRAWN: Letter to the Editor.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Lessons learned concerning vaccine safety.

The safety of vaccines is an issue that has been with us ever since Jenner, and it will not go away. The author argues that despite what may seem a waste of energy, most proposed relationships between vaccines and reactions must be thoroughly investigated, as some have been proved correct. Investigations that show the putative relationship to be incorrect serve as examples of scientific rigor, which are valuable for the public. The author draws eight lessons for the future from our recent experiences.

The efficacy of whole cell pertussis immunisation: collected data on a vaccine produced in France.

The place of whole cell pertussis vaccines in paediatric immunisation schedules is under re-evaluation by public health authorities in many countries, with the expectation that the newly licensed acellular Bordetella pertussis vaccines will induce fewer adverse events while providing equivalent efficacy. In France, for instance, the CSHPF (Conseil supérieur d'hygiène public de France) recently modified its long-standing recommendation that French children only receive whole cell pertussis vaccine. Consequently, an acellular pertussis vaccine may be used for the first booster, at 16-18 months of age, and should be used for the reinforcing dose at 11-13 y of age. French children, nonetheless, continue to receive whole cell pertussis vaccine for the primary series immunisations at 2, 3, and 4 months, as the only whole cell pertussis vaccine available in France (licensed by Aventis Pasteur) has a long-established record of safety and protective efficacy. A review of its unpublished and published clinical results, obtained from studies throughout the world, demonstrates an efficacy of from 84-100% in six different retrospective analyses or outbreak investigations and a protective efficacy of 92% by clinical trial.

Untruths and consequences: the false hypothesis linking CHAT type 1 polio vaccination to the origin of human immunodeficiency virus.

A book published in 1999 hypothesized that the scientists who worked with the CHAT type 1 attenuated polio strain tested in the former Belgian Congo in the late 1950s had covertly prepared the vaccine in chimpanzee kidney cells contaminated with a simian immunodeficiency virus, which evolved into HIV-1 group M. This paper summarizes the results of the investigation conducted by the author to determine the legitimacy of the accusation. Testimony by eyewitnesses, documents of the time, epidemiological analysis, and ancillary phylogenetic, virologic and PCR data all concur to reject the hypothesis as false and without factual foundation.

Postscript relating to new allegations made by Edward Hooper at The Royal Society Discussion Meeting on 11 September 2000.

At The Royal Society Discussion Meeting, Origins of HIV and the AIDS epidemic, which this issue records, Edward Hooper added two new 'smoking guns' to the accusations published previously in The river. These were proposed as conclusive evidence for the hypothesis that simian immunodeficiency virus-contaminated CHAT polio vaccine caused the HIV-1 group M epidemic. We have investigated the facts in relation to these 'smoking guns'.

Optimization of DNA immunization against human cytomegalovirus.

The immune responses of mice injected with plasmids VR-gB and VR-gB Delta tm expressing the full-length membrane-anchored, or secreted forms of human cytomegalovirus (HCMV)-glycoprotein B (gB), respectively, and VR-pp65 expressing the HCMV-phosphoprotein 65 (pp65) were analyzed. Pretreatment of mice with the local anesthetic bupivacaine did not enhance antibody production, and IFN-alpha co-expressed with the immunizing plasmids induced a moderate increase in the antibody response. However, antibody response was higher in mice inoculated at three sites in the musculus quadriceps than in mice inoculated at one site with the same dose and in the same muscle. pVR-gB Delta tm induced significantly higher antibody titers than the construct expressing the membrane-anchored form of gB, and priming with pVR-gB Delta tm followed by boosting with the gB subunit resulted in high-titer antibody responses. Immunization with VR-pp65 induced dose-dependent CTL responses in about 50% of the mice at a dose of 50 microg. Co-expression of IFN-alpha did not affect the number of responding mice. These findings might be important for optimization of humoral and cellular immune responses to HCMV after DNA vaccination.

Vaccination against cytomegalovirus.

Like varicella zoster virus (VZV), human cytomegalovirus (HCMV) causes disease after both primary and recurrent infections. The former is more serious, particularly in pregnant women, who may transmit the virus to their offspring, with a high risk of mental retardation and deafness. Various experimental vaccines are in development, ranging from live, attenuated HCMV, subunit envelope glycoprotein, poxvirus vectors with CMV genes inserted, and plasmid DANN.

Rubella eradication.

The virulence of rubella virus for the fetus was fully defined between 1963 and 1965 when an epidemic of rubella occurred in Europe and the US, followed by a wave of damaged babies. Attenuated live virus vaccines were developed in our and other laboratories and their use has already considerably changed the epidemiology of rubella. Nevertheless, only about half of the world's countries vaccinate against rubella. We argue for the combination of rubella vaccine with measles vaccine in all campaigns for the control of measles, and will discuss the strategies by which congenital rubella syndrome could be eradicated at little additional cost.

Vaccines in the 21st century.

Steffens was wrong about the Soviet Union, and I may well be wrong about the future of vaccines; however, in Table 13, I give my [table: see text] prediction of the vaccination schedule of the next century. It is an optimistic vision, so let us hope that I am right.

CHAT oral polio vaccine was not the source of human immunodeficiency virus type 1 group M for humans.

A book published in 1999 hypothesized that the scientists who worked with the CHAT type 1 attenuated poliomyelitis strain, tested in the former Belgian Congo in the late 1950s, had covertly prepared the vaccine in chimpanzee kidney cells contaminated with a simian immunodeficiency virus, which evolved into human immunodeficiency virus type 1 group M. This article summarizes the results of the investigation conducted by the author to determine the legitimacy of the accusation. Testimony by eyewitnesses, historical documents of the time, epidemiological analysis, and analysis of ancillary phylogenetic, virological, and polymerase chain reaction data all indicate that this hypothesis is false.

Immunologic correlates of protection induced by vaccination.

Vaccine design and licensing depend on the choice of protective antigens and the demonstration of their efficacy. Ideally efficacy correlates with some measurement of immune response, although occasionally the correlation is weak and in the case of some vaccines uncertain. This paper attempts to review what is known about correlates of vaccine-induced protection. Although mucosal and cellular immune responses are clearly important to protection by some vaccines, most vaccines licensed today depend for their efficacy on serum antibodies. Particular levels of antibodies can be identified that confer protection most of the time. A condition for the efficacy of antibodies is functionality, i.e. their ability to kill or inactivate pathogens. The immune system is redundant, and the different types of responses to vaccines act synergistically.