Solutions for Science
As outlined in Chapter 3, “The Elements for Success Are Moving into Place,” the efforts of many investigators throughout the world have laid the foundation for the development of effective malaria vaccines. Recognizing that discoveries in basic science could render any current approaches obsolete and that there is no way to predict whether such discoveries will or will not occur, the following question needs to be answered before the next steps are identified:
What is the most appropriate and efficient way to capitalize on previous work to achieve the objective of fielding effective malaria vaccines?
There was general consensus among workshop participants that the focus of the malaria vaccine effort during the next five years should be directed toward development of two separate vaccines with the following characteristics:
a vaccine that protects at least 90 percent of nonimmune visitors to malarious areas against the development of clinically manifest P. falciparum infection for 12 months or longer;
a vaccine that—when administered to children at 1, 2, and 9 months of age—reduces malaria-specific mortality in the first 6 years of life by 50 percent.
It was agreed that the first vaccine would meet the needs of the private and military markets. The second vaccine would meet minimum efficacy levels for highly endemic regions of the developing world. A single vaccine could conceivably meet both requirements, but participants acknowledged that cost considerations, as well as immunologic and epidemiologic differences in vaccine requirements, justify setting two separate goals for vaccine development.
A number of avenues need to be explored. For example, because Plasmodium is a complex, multistage microorganism, one premise holds that malaria vaccines will have to optimally induce both protective antibodies and CD4+ and CD8+ cytotoxic T-cell responses. Because we already have a validated system for testing preerythrocytic and sexual-stage vaccines in human volunteers by mosquito challenge, as well as defined protective immune
mechanisms and antigens, malaria vaccine development can be used as a model for testing new vaccine technologies that should be of interest to industrial partners.
Work with malaria vaccines has broadly advanced the field of vaccinology, although it has thus far failed to identify a successful vaccine against malaria itself. The first Escherichia coli–produced recombinant protein vaccine ever tested in humans was a malaria vaccine. The first synthetic peptide carrier conjugate vaccine tested in humans was also a malaria vaccine. The first assessment of DETOX (monophosphoryl lipid A and cell wall skeleton of mycobacteria) as an adjuvant for a vaccine against an infectious agent was made with malaria antigens. The first successful use of liposomes with monophosphoryl lipid A as a delivery system (adjuvant) in humans was in a malaria vaccine, and several new adjuvant formulations are now being tested in humans. The first multivalent recombinant vaccinia tested in humans was a malaria vaccine, and an early recombinant S. typhi vaccine tested in humans was a malaria vaccine.
While no one can predict what a final successful malaria vaccine will be, workshop participants generally agreed that the elements for scientific success are moving into place. What is most needed now is a focused, systematic, and multisectoral approach to vaccine development that, as a first step, identifies the scientific hurdles remaining and the funds that will be required to overcome them. In the absence of an established, coordinated strategy, however, such assessments will have little validity and will understandably lack credibility.