Joy as Phase I Meningitis vaccine trial is completed
The trial was conducted by the Meningitis Vaccine Project (MVP), a partnership between the World Health Organization (WHO), the Seattle-based non-profit organisation Programme for Appropriate Technology in Health (PATH) and the Serum Institute of India Limited (SIIL). The MVP was established in May 2001 through a US$70 million seed grant from the Bill & Melinda Gates Foundation. The mission of MVP is to eliminate epidemic meningitis as a public health problem in sub-Saharan Africa through the development, testing, introduction, and widespread use of conjugate meningococcal vaccines.
Following the successful completion of Phase I clinical study, SIIL and MVP will proceed to test the improved vaccine in Africa, where it will become part of the public health arsenal in the fight against meningococcal epidemics that have been plaguing the continent for more than 100 years. “We believe in health for all and in reaching out to the poorest countries in the remotest places of the globe,” said Dr. Cyrus Poonawalla, SIIL chairman, adding: “We are pleased to have embarked on this adventure because this new conjugate vaccine could make a real difference for African countries, some of which are among the poorest in the world. In addition, since the vaccine will be licensed in India, it could also be used in this country, where small outbreaks of serogroup A meningococcal disease occur sporadically.”
Meningitis is an inflammation that occurs in the meninges or linings of the brain. This can be due to infectious processes as well as non-infectious inflammatory conditions. The most common forms of Meningitis are caused by viruses. Less commonly, bacteria produce meningitis. Fungal infections and Tuberculosis can also lead to Meningitis, although these are less common. Initial symptoms often include high fever, sensitivity to light, confusion, headaches and vomiting. The symptoms are usually more severe in bacterial Meningitis. Stiff neck, nausea and vomiting, seizures and localized neurological symptoms can occur. Meningococcal meningitis often produces a red, flat rash.
The average incubation period is 4 days, ranging between 2 and 10 days. The severity of Meningitis lies in the fact that even when the disease is diagnosed early and adequate therapy instituted, up to 10 per cent of the patients die, typically within 24-48 hours of onset of symptoms. About 20 per cent of survivors will suffer from significant neurological sequelae, including mental disorders, deafness, palsies and seizures. Extensive tissue necrosis, sometimes resulting in amputations, may also occur. A less common but more severe (often fatal) form of meningococcal disease is meningococcal septicaemia, which is characterized by a haemorrhagic rash and rapid circulatory collapse. There are two drugs that are used to treat meningitis: oily chloramphenicol and ceftriaxone. The cost of these agents ranges between $2 and $5. Whereas they are quite effective in treating cases of meningococcal meningitis, their cost is beyond the reach of ordinary Africans.
The underlying technology for the new conjugate vaccine was developed by the Centre for Biologics Evaluation and Research of the Food and Drug Administration in the United States. The new vaccine is expected to be more effective than the existing polysaccharide meningococcal vaccines because of its high immunogenicity in young children and its ability to prime immunologic memory, reduce carriage of the bacteria, and induce herd immunity (whereby transmission of the bacterium is blocked, thus extending protection to the unvaccinated). The current polysaccharide vaccines do not work in children under 2 years of age, they provide protection for only 2 to 3 years, and do not confer herd immunity. Conjugate vaccines like the meningococcal A conjugate vaccine, on the other hand, can be used in young children and last longer (10 years or more).
“Our Phase I clinical results are extremely encouraging and open the prospect to start pivotal Phase II clinical studies in The Gambia and Mali later this year after approvals from all regulatory authorities,” said Dr. F. Marc LaForce, MVP director. “If all continues to go well in testing, the new vaccine, which will be priced at about US 40 cents per dose, could be introduced in Africa within the next three to four years.”
The Phase I study was designed to determine the safety and immunogenicity of the new “PsA-TT” conjugate vaccine in healthy volunteers enrolled at three clinical sites in India: B.Y.L. Nair Hospital (Mumbai), King Edward Memorial (KEM) Hospital (Mumbai), and Nizam's Institute of Medical Sciences (Hyderabad). A total of 74 subjects participated in the double-blind, randomized study that compared the PsA-TT vaccine to a reference vaccine currently used to fight epidemic meningitis in sub-Saharan Africa and to a control vaccine that is commonly used against tetanus. The new conjugate vaccine proved to be safe and as immunogenic as the comparator polysaccharide (un-conjugated) vaccine.
“The teams at three study sites worked diligently and carefully, and the results show that the PsA-TT conjugate meningococcal vaccine can be safely administered to humans, and that the new vaccine is immunogenic,” said Dr. Nilima Kshirsagar, dean, professor, and head of the department of clinical pharmacology and principal investigator at Seth GS Medical College & KEM Hospital. “We are all proud to have been able to contribute to the development of a vaccine that is critically needed in Africa.” iGATE Clinical Research International, a full service contract research organization in Mumbai, provided data management and clinical monitoring services for the study.
Several trials of meningococcal conjugate vaccines have been done in Africa: one in The Gambia in the early 1990s, and one in Niamey, Niger, in the mid-1990s. Those trials, particularly the one in Niamey clearly showed that the conjugate A/C vaccine inferred memory and excellent antibody response in infants under two years of age.
The most prominent groups of meningococci are A, B, C, Y, and W135. While groups A, B, and C are responsible for the majority of cases worldwide, group A causes deadly explosive cyclic epidemics predominantly in what is known as the African “Meningitis belt,” an area that stretches from Senegal and the Gambia in the West to Ethiopia in the East. The belt has an at-risk population of about 430 million. Every year, epidemics kill thousands of people.
In 1996–1997, Africa experienced the largest recorded outbreak of epidemic meningitis in history, with over 250 000 cases and 25 000 deaths reported to the WHO. “Meningococcal epidemics hit the African belt in seasonal waves, every 8 to 12 years,” explained Dr. James Mwanzia, director of communicable disease prevention and control at the WHO regional office in Harare, Zimbabwe. “The largest epidemic wave ever recorded swept across the entire region 10 years ago. Even though sub-Saharan Africa has been relatively spared in recent years, we know from experience that it is just a matter of time for another large epidemic to hit the region again.” According to Dr Mwanzia, a sharp meningococcal A epidemic is currently occurring in western Burkina Faso, with some 3 000 cases reported.
“Because the disease occurs in children, adolescents, and young adults of working age, the disruption and chaos in the community are considerable,” said Dr. Kader Konde, WHO focal point for MVP. “The impact of the disease on individuals and their families is such that an epidemic can quickly turn into a social, human, and economic disaster for the affected countries. Meningitis is one of the most feared diseases on the African continent, and the new conjugate vaccine brings real hope that huge epidemics like that of 1996 will be a thing of the past.”
Residents of the Kenyan Rift valley town of Kapenguria, which is prone to Meningitis outbreaks could not hide their joy on hearing of the new development. “This is the greatest news I have received in a lifetime. Meningitis has killed a lot of our people and I can only thank God for the new vaccine that is on the way”, remarked 50-year-old Paul Lopokoyit. His sentiments were echoed by Mrs Mary Lepeitan, 38, who recently lost her husband and son to Meningitis. Said she: “A new vaccine will surely be good news as it is the only way to contain Meningitis. The drugs being sold are too expensive and most of us can’t afford them”.