VANCOUVER, British Columbia Creative vaccine distribution
strategies, improved vaccine technologies and more rapid manufacturing
timetables were among ideas speakers at the 2010
Pediatric Academic Societies proposed during a symposium on
vaccine-preventable diseases in the developing world.
Kathleen M. Neuzil, MD, MPH, professor of medicine at the
University of Washington, senior advisor for immunizations at PATH, both in
Seattle, and Advisory Committee on Immunization Practices member said that the
lessons learned during this past seasons influenza A (H1N1) pandemic can be applied to
distributing vaccines to people in low-resource settings.
The virus was detected and characterized in record time,
manufacturing capacity was at all time high and there were rapid organization
and distribution efforts, Neuzil said. But we didnt have
enough vaccine, we didnt get it out soon enough and distribution was not
She noted that although H1N1 peaked during the third week of October in
2009, many physicians offices did not get the vaccine until much later, and
many developing countries are just now getting their first allotment of H1N1
As director of PATHs Influenza Vaccine Project, Neuzil and
colleagues are exploring live-attenuated, recombinant and adjuvant vaccine
approaches, as well as more broadly reactive antigens that offer more
cross-protection, with longer-lasting immunity than the typical one or two
Most of these are still in very early development, Neuzil
Although the United States and Canada now have universal influenza
vaccine recommendations, Neuzil acknowledged that this is a difficult goal to
achieve, and highly unpractical for many countries.
Taking a high risk approach may be a more logistically sound strategy.
Data from a randomized controlled trial that involved 340 pregnant Bangladesh
women who received influenza vaccine, revealed that babies whose mothers
received vaccine experienced a 28% reduction in illness compared with the
Furthermore, influenza specific antibodies were higher among vaccinated
mothers and infants, and infant geometric mean titers sampled at birth from
cord blood were comparable to levels measured in the mothers serum,
according to Neuzil.
The PATH Initiative, in cooperation with the CDC, is currently
evaluating the feasibility of vaccinating all 6-week to 10-week-old children in
a village in Senegal to determine if this strategy will prevent influenza in
the broader community. Last year, teams vaccinated about 86% of the village,
and 98% of those who were supposed to receive a second vaccine did.
Despite these successes, Neuzil noted that researchers have a lot to
learn. Improving this technology so that it is no longer a yearly
vaccination program will make a much more realistic strategy in many of these
Similar to the influenza vaccine, rotavirus vaccines are widely successful in the United
States, but pose problems in developing countries, Roger Glass, MD,
PhD, of the National Institutes of Health and the CDC viral
gastroenteritis unit at the CDC, told audiences here.
Despite the fact that these vaccines have greatly reduced U.S.
hospitalizations attributable to diarrheal illness with efficacy rates ranging
from 85% to more than 90%, vaccine performance remains suboptimal in low-income
Early findings from oral rotavirus vaccine use in developing countries
show that immune responses correlate directly with the level of development of
the country in which the vaccine is administered. Therefore, children in poorer
countries were less likely to have good immune responses, Glass explained,
similar to previous experiences with oral poliovirus vaccine.
The first studies of the live-attenuated oral monovalent rotavirus
vaccine (Rotarix, GlaxoSmithKline) in South Africa indicated that only 36% of
children aged 6 to 10 weeks developed an immune response.
Similarly, M. Patel et al determined that in Nicaragua, 76% of 200 infants who
were admitted to the hospital with rotavirus diarrhea had been vaccinated
against the disease with the pentavalent rotavirus vaccine (RV5, Rotateq,
Merck) compared with 83% in the control group, putting the efficacy of this other vaccine efficacy at only 46%.
Furthermore, additional studies with RV5 completed in five different
developing countries Bangladesh, China, Kenya, Mali and Vietnam
demonstrated that vaccine efficacy ranges from 1% to 72%, much lower than rates
in countries such as the United States and Europe.
Researchers believe that interference from maternal antibodies may be
partially to blame, according to Glass. Data from a study involving vaccine
recipients in Finland indicated that those who failed to respond had
significantly higher maternal antibody titers at the time of vaccination,
suggesting that this transplacental antibody may impede a childs immune
response to the vaccine.
Glass said that many other factors may also interfere with immune
responses, but that these remain poorly understood. In the meantime, several
solutions have been proposed to overcome these issues, including delaying
vaccination, increasing the potency of vaccine doses and withholding
breastfeeding for a specified amount of time.
Additionally, two rotavirus strains that may be able to grow in the
presence of maternal antibody are currently in development for a neonatal
version of the vaccine 116E in India and RV3 in Australia.
An inactivated, parenteral form of rotavirus vaccine is also under
consideration. Inactivated rotavirus vaccine is one way of having more
uniform efficacy between children in developed and undeveloped countries.
Inactivated vaccines are safer from intussusception, would not have same age
restrictions, would cost less to develop and could be combined with other
vaccines, making them easier to delivery, Glass said. He noted that need
for a research agenda to determine why oral rotavirus vaccines are less
effective in developing countries was an urgent.
Weve clearly come a long way with rotavirus vaccines, but we
still have a long way to go to stop death of 600,000 children per year,
Glass said. by Nicole Blazek
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