Category Archives: Vaccine

Vaccine without pain – a future for malaria control

During a discussion organized the Bill and Melinda Gates Foundation, Chris Wilson explained that vaccines are one of most efficient and effective interventions ever developed. Among the discussants was Tycho Speaker who is doing research on transdermal delivery systems using microneedle systems.

Dr Speaker is the primary contributor in developing TransDerm’s proprietary soluble microneedle technology, which is finding utility in skin therapeutics and skin-based vaccinations. This vaccine research has received specific funding for malaria prevention from the Bill and Melinda Gates Foundation under their Grand Challenges Explorations program.

phase-iii-rtss-trials-dave-poland-path-malaria-vaccine.jpgChris Wilson emphasized that, “We need to do better job to ensure vaccines reach people who need them and increase coverage.” The microneedle patch technology may be able to achieve this for malaria vaccines that are in the pipeline.

Normally such technology may take ten years from conceptualization to actual use in the population. Gates has given Dr Speaker’s group a preliminary one year grant to test the concept, and then there is the possibility for a second grant to develop the practical applications of the microneedle patch if the results are encouraging.

The patch actually resembles a bandaid. The microneedles penetrate the skin and dissolve so there is no medical sharps waste. The vaccine itself in made into a powdered form and is stable without the need for coldchain.  The speakers stressed the practicality – the patch vaccines could even be transported on motorcycle to peripheral health facilities that have no electricity.

The patches can be printed with a picture or pattern that appeals to children and parents to address the perennial vaccine problem of community acceptance.  Within 2-10 minutes the vaccine will be delivered.

The discussants concluded that a small increase in compliance can have enormous effect on the vaccination effort overall, especially when there is no pain. It’s good to know that researchers are not simply looking for an effective malaria vaccine, but also for delivery mechanisms that will make the vaccines more acceptable and actually used.

Introducing the International Vaccine Access Center

ivac_logo_wtaglinefinal_resized.jpgBefore reaching her second birthday, an American child will be vaccinated against 14 diseases. A child in sub-Saharan Africa? About 6. Yet the African child will be especially vulnerable to disease due to high rates of malnutrition, co-morbidities, and weak health systems.

What’s more, the American child will have access to new vaccines as they become available. After a 15 to 20 year lag, those same vaccines will finally reach sub-Saharan Africa, perhaps in time for the next generation.

The International Vaccine Access Center, which launches on December 7, seeks to change this scenario by accelerating global access to life-saving vaccines. Vaccine uptake is delayed by a combination of incomplete epidemiological information, outdated policies, and market barriers. For instance, without information on country-specific disease burdens, policymakers are left weighing the upfront costs of revising their immunization program against uncertain future benefits.

As national policies remain unchanged, the potential market looks smaller and smaller to manufacturers. Without confirmed orders, manufactures cannot offer the reduced pricing that makes these products affordable to developing countries.

In the meantime, years pass and kids succumb to diseases that could have been prevented. The 2009 State of the World’s Vaccines and Immunizations Report estimates that existing vaccines could avert the deaths of up to 2 million children if given access to these vaccines.

IVAC sees an opportunity to save lives by shortening the lead-time between vaccine development and vaccine introduction in the developing world. Building on lessons learned from the successful Hib Initiative and Pneumococcal Vaccine Accelerated Development and Introduction Plan (PneumoADIP), IVAC will generate the epidemiological information policymakers need to make informed decisions. “For too long, access to life-saving vaccines has been delayed by the lack of evidence-based policies to support their use and delivery.

The cost of these delays is measureable in lives lost, and IVAC will aim to turn that situation around by using evidence to assure equitable vaccine access globally,” said Orin Levine, Executive Director of the new center.

ivacmodel2.jpgBased at the Johns Hopkins School of Public Health, IVAC will strive to maximize the impact of immunizations, one of the most powerful and cost-effective tools we have for improving child health. Hopefully, success will build upon success, demonstrating to manufacturers the viability of new products in developing markets and generating new investments in child health. While IVAC does not have an official malaria project as of yet, the center is exploring opportunities to accelerate the introduction of a future vaccine.
To learn more about IVAC and childhood vaccination, visit Dr. Levine’s blog at the Huffington Post.

Thanks to Jenna Rose for providing the above information.

Malaria vaccine enters phase 3 clinical trials

A new malaria control tool is closer to joining the arsenal of malaria interventions according to vaccine researchers and their sponsors at a press briefing today during the MIM 5th Pan-African Malaria Conference in Nairobi.

A joint venture between PATH’s Malaria Vaccine Initiative and GlaxoSmithKline Biologicals, with support from The Bill and Melinda Gates Foundation, WHO and African Governments and the participation of African malaria researchers at 11 sites in seven countries has recently completed a successful Phase 2 Clinical Trial of the RTS,S vaccine.

vaccine-and-malaria-life-cycle-sm.jpgMozambique, one of the Phase 2 trial sites reported that, “vaccine efficacy against new infections was 65 percent over a three-month follow-up period after the infants received all three doses of the vaccine. The results also showed that the vaccine reduced episodes of clinical malaria by 35 percent over a six-month follow-up period starting after the first dose.” At the Ghanaian study site it was confirmed that “Three dose schedules were more immunogenic than 2 dose schedules.”

Joe Cohen of GSK Biologicals explained at the press conference that vaccine efficacy in children 5-17 months was 53% after 8 months. The trials also showed that the new vaccine can be integrated into the EPI vaccine process.  Continuing research will determine if it will also be effective in younger children.
Phase 3 trials have started and have already enrolled 5,000 of the expected 16,000 volunteer participants. Reporters were anxious to know when the vaccines might actually be available for general use. The panelists outlined steps that included filing results of Phase 3 and previous trials with regulatory agencies around 2012. If approved, vaccines could be available around 2015. In the meantime partners are gearing up to find funding to support adequate production.

Christian Loureq of the PATH Malaria Vaccine Initiative said that partners ranging from researchers, producers and funders were all thinking ahead.  No one wants the vaccine to sit on the shelf after proving its efficacy.  A decision making framekwork is helping planners identify the data and resources needed to start rolling our vaccines on the day they are approved.

As noted, the partners recognize that an effective vaccine will be only one of the needed interventions to sustain malaria control, especially since the efficacy, though good, is not perfect. Thus, they are already thinking about research for the next generation of vaccines for 2020 or 2025

A key component to planning roll-out is research for understanding the community perspective, recognizing that the mothers who brought their children to the trials are also central partners in this initiative. The EPI program itself is full of lessons about acceptance and dropping out. The 3-dose vaccine regimen will certainly pose many implementation challenges, but hopefully the malaria community will be ready to tackle these.

Malaria immunization involves more than an effective vaccine

On Wednesday the Globe and Mail reported on efforts of a malaria vaccine trial in the Kenyan coastal district of Kilifi.  The researchers are happy that the “vaccine reduced the risk of clinical episodes of malaria by 53 per cent over an eight-month period.”  According to GSK, “large-scale phase lll vaccine efficacy trials in seven African countries across 11 sites. If these trials confirm the safety and efficacy of the candidate vaccine, it could be filed for registration.”

The villagers in Kilifi may have other concerns. Zoe Alsop in the Globe and Mail outlines several of these:

  • the Caduseus medical symbol on project vehicles contains a snake, but this is a ‘demonic symbol’ to the villagers
  • as a research project, blood samples are taken, but villagers fear this is ‘a lot’ and may be used for evil purposes
  • villagers are generally skeptical because of “a long history of neglect and corruption in Kenya’s public health-care sector and government in general”
  • people do not fully understand the nature of research trials and believe the vaccine is already approved

dsc00765-sm2.JPGThe researchers are facing the practical problems of any drug trial in communities that do not have good experiences with or full understandings of the workings of western science.  ‘Meticulous explanations‘ may not be enough to overcome fears, and trust can be shattered when a person in a control group gets sick from the drug that was supposed to prevent or heal. The process of signing formal consent documents itself may cause suspicion.

Vaccine programs over the years have faced their own hurdles, even when the offered on a regular basis.  One only has to witness the enormous challenges that the polio vaccine effort confronted in the face of widespread community resistance in Nigeria.  Ordinary occurrences such as side effects like fever or redness/pain at the immunization site discourage people.

Then there are the unethical research practices like Pfizer’s testing of a meningitis antibiotic in Kano, Nigeria that result in death and widespread fears of any future effort to help people.

The malaria vaccine researchers have conducted the perfunctory meetings with village chiefs and village information sessions.  It is not clear if the team involved social scientists in advance to learn more about people’s views and experiences of malaria and vaccines and engage the community in full dialogue about these issues.  It is not too late, but a word to the wise for any health research or intervention program: learn from the people first before you can expect them to learn something new from you.  These villagers have lived in the community for generations and will be left behind when your program finished – show them some respect, and your own efforts will be rewarded.

Creating health systems to support malaria vaccine research

Various announcements have been made this week of a huge upcoming malaria vaccine trial among 16,000 African children. The Seattle Times describes the major health systems investments that have been underway to support this research trial.

The massive vaccine trials will be conducted in Burkina Faso, Gabon, Ghana, Kenya, Malawi, Mozambique and Tanzania. Dr. Christian Loucq, director of the Malaria Vaccine Initiative, said the project has been working over the past year to upgrade laboratory, computer and other equipment in those countries, train technicians, and even help develop local equivalents of the U.S. Food and Drug Administration to ensure the trials are properly monitored.

dscn1189sm.JPGThis is a indirect acknowledgment of the broader health systems challenges that create bottlenecks for implementing existing interventions such as long lasting insecticide treated nets, artemisinin-based combination therapy and intermittent preventive treatment for pregnant women.  The success of these current interventions is essential for bring malaria levels close to elimination levels in endemic countries so that when an effective vaccine arrives, it will be able to carry malaria control efforts to the next level – eradication.

GlaxoSmithKline, one of the vaccine trial partners, has an active malaria support program that addresses malaria prevention and treatment activities in 8 African countries and so is very likely aware of the systems challenges facing implementation of existing interventions. The researchers are also realistic about their own challenges because they have been involved in malaria vaccine trials since 2003.  The PATH Malaria Vaccine Initiative, the other partner in this endeavor, has other vaccine candidates in the pipeline ‘in case’.

Ultimately, the researchers realize that “even if their vaccine does not succeed, the widespread investment needed to conduct the trials means that Africa will be left with better communications, research and other infrastructure that could be used in the search for vaccines against other diseases such as AIDS.” What is needed though is ongoing, more thorough and concerted attention to improving health systems to deliver malaria and other primary health care interventions, not just building systems when and where a special research project is planned.

Better access to and use of health systems strengthening funds from the Global Fund is one step in this direction.

Malaria vaccine concerns

Sobering thoughts arise when contemplating the review of HIV vaccine failure in the Washington Post. Not only have vaccine candidates to date failed, there is even evidence that they put people at greater risk by stimulating receptivity of target cells to HIV invasion. Have decades of research dollars, notably over $500 million, been wasted? The Washington Post quotes Robert Gallo, co-discoverer of the human immunodeficiency virus, as saying “This is on the same level of catastrophe as the Challenger disaster” (the NASA/USA Space Shuttle disaster).

Efforts to find a malaria vaccine have also spanned decades. A new review of the status of malaria vaccine research by Pizon-Charry and Good concludes that, “the disappointing results of clinical trials have resulted in reappraisal of current strategies. Whole-parasite approaches have re-emerged as an alternative strategy.”

The Malaria Vaccine Initiative (MVI) is a little more upbeat about vaccine prospects and feels that “government, industry, and academia partners” may be able to solve the problem. At the same time they do caution that, “There has, however, never been a vaccine developed against a complex multi-stage parasite. Since malaria is caused by such an organism, developing a vaccine to prevent it is especially challenging.” While MVI talks of accelerating malaria vaccine development, it appears cautious also on predicting a date when such may become a reality.

Much of the talk of malaria eradication seems based on the assumption that a malaria vaccine will be in place at some time in the foreseeable future. We hope researchers succeed sooner than later. In the meantime people should not put away their bednets and stop the search for new anti-malaria drugs. At least so far the existing malaria vaccine candidates do not appear to have increased people’s risk of getting malaria.

Malaria Vaccine Progress in Mozambique

Success of another malaria vaccine candidate is being celebrated. According to the New Scientist, “A vaccine against malaria would save hundreds of thousands of lives each year. Now it seems we’re much closer to finding one.” The report in The Lancet by Aponte et al. explains that the vaccine trial in Mozambique after three doses at 10 weeks, 14 weeks, and 18 weeks of age, “Vaccine efficacy for new infections was 65% over a 3-month follow-up after completion of immunizations. This efficacy estimate is higher than the 45% reduction reported in a previous trial in older children.”

Also of note, serious adverse events and side effects were not significantly different from the control group children who received Hepatitis B vaccine in addition to the normal childhood immunizations. BMJ News observed that, “This early trial was focused on safety. Bigger trials to assess efficacy could be next.”

Ultimately, any successful vaccine needs to address social and organizational issues in addition to safety and efficacy. The best health technologies are useless if people do not adopt them correctly. The fact that this new vaccine candidate could be integrated into a normal childhood vaccine schedule may address some of the organizational concerns, and the similar level of reactions to existing vaccines may help with acceptability concerns.

Consumer expectations and beliefs may provide additional hurdles. Malaria endemic communities have many ideas about what constitutes ‘malaria’. Various conditions ranging from ‘ordinary’ malaria to yellow fever and typhoid have been conflated under the umbrella of ‘malaria’ illness in parts of West Africa. That coupled with the fact that as currently constituted, this vaccine candidate may leave 35% of children unprotected may raise doubts in the community about the perceived efficacy of the shots.

One cannot blithely say, “Health education will handle such problems.” Health educators cannot convince people to adopt something that runs strongly counter to their experiences. The answer therefore is for researchers to continue to work (with increased donor funding) to perfect the malaria vaccine candidates and make them more acceptable to the public. Only when there is a dialog between the public and public health professionals and researchers can innovations that are both efficacious and acceptable be developed.