Bird flu: reducing vaccine dosage to cover more people

Published in The Hindu on June 28, 2007

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More study is needed before undertaking this strategy. Cross-protection between two clades is limited. — Photo: Wikipedia

Even as Indonesia has forced the World Health Organisation to find ways to provide access to bird flu vaccines by developing countries when a pandemic strikes, the current limited capacity to manufacture the vaccines is worrying. This turns the spotlight on the strategies that can make vaccines available to a larger population when needed.

One way would be to have manufacturing facilities in developing countries. This being a time consuming process, there is a compelling need to find alternative strategies.

With a current capacity to manufacture 350-400 million doses of bird flu vaccine, which can meet the requirements of just about 6.6 billion people, researchers are looking at maximising the utility of the existing vaccines to cover a larger population.

Even after increasing the capacity to 780 million doses by 2009, as proposed by the WHO, a large section of the world’s population would still have no access to vaccines.

Antigen sparing

In a paper published in the latest issue of PLOS Medicine, researchers from the University of Hong Kong have looked at reducing the dosage level for the said purpose.

Using computer modelling, they found that antigen sparing — reducing the dose administered thereby increasing the number of people vaccinated — in a community-based programme will, for example, help cover 160 million of the 300 million in the U.S. When used at the current recommended dose, only 20 million can be vaccinated.

Herd immunity

They argue that instead of providing individual-level protection, a population-level protection works better. They note that “…lower individual doses, conferring less than maximal protection for those vaccinated, may provide substantial incremental community-level benefit…”

Surely, some level of immunity compared with no immunity is better. Consider a situation where many residents in Indonesia are immunised by the strain that is currently infecting and killing people there.

If a pandemic were to happen, the herd immunity — where not only the vaccinated individuals but also those who come in contact with such people stand to gain — can reduce the mortality and morbidity rate. But considering the high rate at which the H5N1 mutates, if another strain where to cause the pandemic, the pre-pandemic vaccination may be of little use.

And again, can compromised pre-pandemic community-based vaccination facilitate the faster mutation of the H5N1 virus? New strains emerged in China when large-scale vaccination in the poultry was undertaken. A perspective piece published in the same issue of PLOS Medicine reflects the same views.

“The circulating virus will not be the currently known avian H5N1, but rather a newly human adapted strain,” it notes. It also underlines that “…the match between vaccines based on an avian virus and one based on a human-adapted pandemic strain is unknown.”

It further adds that the relation between the vaccine titres and the actual protection they offer is not clearly known. And this only further complicates the issue.

With Indonesia continuing to remain a hotbed for H5N1 outbreaks and accounting for the maximum number of people being infected and nearly 80 dead, the chances of the strain continually mutating is quite high. So the need to immunise people with pre-pandemic vaccines prepared with the new strains will be needed.

With an emphasis on pre-pandemic vaccination, developing countries’ ability to stockpile vaccines that can be effectively used when a pandemic actually strikes will be greatly compromised.

It is well known that clade 2 H5N1 virus circulating in Indonesia is different from clade 1 that is seen in Vietnam. Clade is a group of organisms that have evolved from a common ancestor. “Preliminary evidence …suggests that cross-protection between these two influenza A (H5N1) clades may be limited,” noted an Editorial published in the New England Journal of Medicine.” This further compounds the problem.

Vaccine trial

The results of a H5N1 vaccine trial published last year in the New England Journal of Medicine show that greater immune response was seen when relatively high doses were used. Two doses of 90 microgram produced (neutralising) antibody titters of 1:80 or more in 56 per cent of volunteers.

“…our [study] shows that high doses of relatively purified protein vaccines were required to induce immunity in most recipients,” the authors conclude.

They also point out that “dose-sparing approaches should be pursued aggressively” as producing vaccines of 180 microgram will severely limit the number of beneficiaries.

An Editorial in the same issue of the New England Journal of Medicine echoes the views of the researchers from the University of Hong Kong.

“The immediate development and testing of antigen-sparing vaccines administered with adjuvant [a substance added to increase the effectiveness of a medicine] are imperative both to improve immunogenicity [immune response] and to increase the number of doses available (if lower doses are effective),” it notes.

More data needed

Despite the several limitations of the Hong Kong researchers, it is worth investigating it further as any strategy that would eventually help in protecting more people when a pandemic strikes should not be overlooked.

The Editor’s summary published alongside the paper published in the PLOS Medicine points out: “…need to know whether pre-pandemic vaccines actually provide good protection against pandemic virus… before they recommend mass immunization with low doses of pre-pandemic vaccine, selective vaccination with high doses, or a mixed strategy.”