Search For Strain-Specific Meningococcal Vaccine
21 March 2002 Media Statement
Search For Strain-Specific Meningococcal Vaccine On Track
Health Minister Annette King says the signing of a second contract with biotechnology company Chiron illustrates the Government’s commitment to developing a vaccine targetting the New Zealand-specific strain of meningococcal group B bacterium.
The Ministry of Health signed an initial contract with Chiron Corporation last year to begin manufacturing a tailor-made vaccine for New Zealand. The second contract, signed today at a function in Parliament, clears the way for the Ministry and Chiron to implement an action plan, including a series of clinical trials prior to an expected nationwide roll out of an approved vaccine.
The Government gave the go-ahead to the project in January, with an announcement of $100 million-plus funding. “Today is very much a milestone, because it offers tangible evidence of the Government’s commitment to funding the programme to develop and roll out a vaccine to end the meningococcal epidemic in New Zealand,” Ms King said.
“This epidemic has cost our society $630 million to date, with direct costs to the health sector estimated at $300 million. This doesn’t include the human costs associated with death and loss of quality of life for people affected by meningococcal disease.
Ms King said now there was a commercial partner fully on board, planning could begin for the first stage of clinical trials in mid-2002. This would involve testing a safety-approved vaccine on adult New Zealanders recruited from the health profession. Pending a successful Phase I trial, another set of trials would be run at the end of the year within the target group – under 20-year olds. The entire process is expected to take at least 18 months.
All people involved in clinical trials will be closely monitored by health professionals under rigorous regulations laid down by Medsafe and regional ethics committees.
Ms King said 648 people contracted meningococcal disease last year, and 26 died. An estimated 20 percent of all cases were left with some degree of disability/brain damage, deafness, loss of limbs, or the results of skin grafts to repair damaged skin.
“We have a big challenge in front of us to establish that this vaccine will be effective, but this vaccine strategy holds the greatest hope of bringing this epidemic under control. In the meantime, the people of New Zealand need to remain vigilant and learn the early symptoms of meningococcal disease in order to seek early treatment.”
information, contact John Harvey (04) 471
Group B Meningococcal
Bacterial group B meningococcal disease can cause septicemia (commonly known as blood poisoning), meningitis (swelling of the brain), or a combination of both. Group B meningococcal disease has been experienced in epidemic proportions in New Zealand since 1991, with 2001 being the worst year yet.
In New Zealand, the highest prevalence of meningococcal disease is for serogroup B, for which there is currently no commercial vaccine available. Immunisation programmes in the past have successfully controlled outbreaks of serogroup A and C meningococcal disease.
Last year (2001) the epidemic peaked with 648 confirmed cases. 26 people died as a result while an estimated 20 percent were left with some degree of disability – brain damage, deafness, loss of limbs or the results of skin grafts to repair damaged skin. A further percentage is left with educational and behavioural side effects. There are no signs of the epidemic abating. The specific strain of Meningococcal B disease prevalent in New Zealand is the only notified infectious disease in this country for which there is currently no vaccine.
The ESR (Institute of Environmental Science and Research Limited) reports that since the start of 2002, 63 cases of meningococcal disease have been reported including two deaths. At the same time last year 72 cases and two deaths had been reported. These are only provisional figures and remain well above the expected case numbers for a disease that is usually prevalent during winter and spring months.
Meningococcal disease affects all age and ethnic groups at alarming rates in New Zealand. However, the rates of disease Mäori and Pacific peoples are extraordinarily high, especially in young children. Until a vaccine is widely available, people still need to be aware of the symptoms and to seek medical treatment early. Symptoms in a very young child can include a fever and vomiting, or the child may refuse drinks or feeds, be excessively sleepy, or persistent crying and be unsettled. A rash like blood spots under the skin may also appear at a later stage. It is important that all children see a doctor immediately, as early treatment helps save lives and reduces the disabling effects of this disease.
Further information about meningococcal disease can be found at the Ministry of Health website www.moh.govt.nz
The Meningococcal Vaccine Strategy
A strain-specific vaccine for New Zealand is being produced by Chiron Vaccines in collaboration with the Norwegian National Institute of Public Health (NIPH), which developed a similar vaccine for a group B meningococcal epidemic in Norway in the 1990s.
An initial contract signed with Chiron, on behalf of the Crown, was signed in July 2001 to enable the manufacture of a strain specific vaccine to be developed for New Zealand. A second contract signed on March 21 2002 signals the beginning of a complex clinical trial process expected to begin mid-year and continue for another 18 months. It is anticipated a mass vaccination targeting all under 20-year olds will proceed thereafter once clinical trials and complete and assessed against rigorous safety and effectiveness guidelines.
The vaccine targeting the New Zealand strain of group B meningococcal disease will be tested in New Zealand according to international guidelines on vaccine development. International and national peer review by leading scientific and public health advisors are taking place. This includes in New Zealand assessment by Medsafe, the Standing Committee on Therapeutic Trials (SCOTT) and regional ethics committees. Internationally, scientific leaders in the development of meningococcal vaccines and the WHO are assisting New Zealand in the clinical design and assessment process.
The Ministry of Health is working closely with Chiron and University of Auckland to oversee and manage clinical trials. A Principal Investigator will head the team managing the clinical trials.
Chiron Corporation has experience in developing vaccines against other groups of meningococcal disease, including development of MenjugateTM – which was used in a universal vaccination campaign to prevent group C meningococcal disease in the United Kingdom. This vaccine has also been used in Canada.
Further information about Chiron can be found at www.chiron.com
The Search for a Vaccine
Vaccines effective against serogroup B meningococcal disease have been technically difficult to develop. Currently, there are no serogroup B meningococcal vaccines available for whole population use, vaccines must be produced for specific sub strains, or serogroups of group B meningococcal disease. International experts now have a better understanding of meningococcal B epidemics in which one strain predominates (monoclonal). The New Zealand epidemic is expected to last at least a further 10 years without a vaccine-based health intervention.
There have been group B meningococcal disease epidemics in Brazil, Iceland, Chile, and Norway over the past 15 years. It is encouraging to note that vaccine capability is improving slowly. In the late 1980s Cuba introduced a vaccine to control a different strain of group B meningococcal disease and achieved a 95 reduction in disease within five years.
New Zealand research into the meningococcal disease epidemic and means of prevention and control, including potential vaccines, occurred in 1995 when the rates of disease started to accelerate sharply. As part of this work, an Auckland study group began working on appropriate vaccine study design in 1996.
In 1998, delays in securing a suitable vaccine meant the Ministry of Health requested the assistance of the World Health Organisation (WHO). WHO assisted in attracting research and manufacturing interest to produce a strain specific vaccine for New Zealand. The particular strain of group B meningococcal disease in New Zealand is found in very low quantities overseas, which made any potential New Zealand strain specific vaccine commercially less attractive. A WHO Advisory Group of experts was formed and assisted New Zealand with the evaluation of vaccine proposals while also providing advice on study design.
Requests for proposals attracted the attention of three vaccine institutes that were interested in building competence to develop monoclonal vaccines. The manufacturers were Finlay (Cuba), NIPH (Norway), and RIVM (Netherlands). Baxters Healthcare (US) also expressed interest late in the selection process. International experts were then called upon to help determine the most suitable vaccine provider.
Negotiations with several companies served to highlight issues of cost, ethics, safety and time to develop, trial and manufacture a tailor-made vaccine to target the meningococcal B disease strain prevalent in New Zealand. Prior to any trials, the requirements of the Medicines Act 1981 must first be met. The safety and scientific validity of clinical study protocols of medicines is assessed by the Health Research Council's Standing Committee on Therapeutic Trials (SCOTT). Ethics approval is also required. The Director-General of Health may grant the approval for use of a medicine in a trial after receiving a favourable recommendation from SCOTT and ethics approval.
In 1999 successful negotiations resulted in the Ministry of Health committing to work with Californian-based biotechnology company Chiron Corporation, in association with the Norwegian National Institute of Public Health (NIPH). A formal contract was signed on 31 July 2001 followed by a second contract to develop, trial and manufacture a vaccine on 21 March 2002.
The Government has committed more than $100 million to the development of this strategy. The total cost will include the price of the vaccine, clinical trials, management and administration, education and public communication.
National Prevention and Control of Meningococcal Disease
An important part of the meningococcal disease strategy is to raise and maintain public and professional awareness of meningococcal disease, the symptoms and dangers and what to do about it.
The strategy has six components:
o Intensified epidemiological surveillance
o Promoting public awareness to encourage early medical intervention
o Promoting professional awareness to encourage early diagnosis and treatment
o Prevention of secondary cases by notification, contact tracing and offering prophylactic antibiotics
o Three year case control study to identify modifiable risk factors, and
o Vaccine strategy.
Posters and flyers are available for caregivers and young adults emphasising the message that people need to see a doctor early if they, or someone they know, is sick.
Meningococcal disease may develop quickly, so the important message is – Don't Wait – Take Action. If meningococcal disease is treated early with antibiotics, most people will recover.
Key Public Messages for Meningococcal B Disease
Don't wait – take action: see a doctor if you or your child is sick, and check them often. If your child gets worse, take them straight back to the doctor.
Early treatment saves lives.
Your child may be seriously ill if they:
o Have a fever
o Refuse drinks or feeds
o Are sleepy or floppy or harder to wake
o Are crying or unsettled
o Have a rash/spots
o Have a headache.
Doctor's visits are free for children under six.
Anyone can get meningococcal disease – though those at greatest risk are children under five and young adults.
LOCATION OF MENINGOCOCCAL DEATHS BY HEALTH DISTRICT BY YEAR
District 1996 1997 1998 1999 2000 2001
Canterbury 1 2 2 1 1
Central Auckland 1 1 3 3 2 2
Eastern Bay of Plenty 1
Gisborne 1 1
Hawkes Bay 2 1 2 1
Hutt 2 2 2 1
Manawatu 1 1 1
Nelson-Malborough 1 3 2
North West Auckland 3 2 1 1 1
Northland 3 2 3 1
Otago 1 1 1 2
Rotorua 1 1
Ruapehu 1 2
South Auckland 3 8 2 5 2 4
South Canterbury 1 1 2 1
Southland 1 1 1 1
Taranaki 2 1
Tauranga 1 1 1 3
Waikato 1 3 5
Wellington 3 1
West Coast 1
Total 18 24 23 22 17 26