The first malaria vaccine candidate (RTS,S/AS01) to reach phase 3
clinical testing is partially effective against clinical disease in
young African children up to 4 years after vaccination, according to
final trial data, published in The Lancet. The results suggest
that the vaccine could prevent a substantial number of cases of clinical
malaria, especially in areas of high transmission.
The findings reveal that vaccine efficacy against clinical and severe
malaria was better in children than in young infants, but waned over
time in both groups. However, protection was prolonged by a booster
dose, increasing the average number of cases prevented in both children
and young infants.
Brian Greenwood, corresponding author and Professor of Clinical
Tropical Medicine at London School of Hygiene & Tropical Medicine in
the UK explains, "Despite the falling efficacy over time, there is
still a clear benefit from RTS,S/AS01. An average 1363 cases of clinical
malaria were prevented over 4 years of follow-up for every 1000
children vaccinated, and 1774 cases in those who also received a booster
shot. Over 3 years of follow-up, an average 558 cases were averted for
every 1000 infants vaccinated, and 983 cases in those also given a
booster dose."
"Given that there were an estimated 198 million malaria cases in
2013, this level of efficacy potentially translates into millions of
cases of malaria in children being prevented."
The RTS,S/AS01 vaccine was developed for use in sub-Saharan Africa
where malaria still kills around 1300 children every day[1]. There is
currently no licensed vaccine against malaria anywhere in the world.
The phase 3 randomised trial enrolled 15459 young infants (aged 6 to
12 weeks at first vaccination) and children (5 to 17 months at first
vaccination) from 11 sites across seven sub-Saharan African countries
(Burkina Faso, Gabon, Ghana, Kenya, Malawi, Mozambique and United
Republic of Tanzania) with varying levels of malaria transmission. In
2014, initial phase 3 results at 18 months showed vaccine efficacy of
about 46% against clinical malaria in children and around 27% among
young infants [2].
In this study, members of the RTS,S Clinical Trials Partnership
followed up the infants and children for a further 20 to 30 months,
respectively, and assessed the impact of a fourth booster dose.
Participants were each vaccinated three times with RTS,S/AS01 with or
without a booster dose 18 months later, or given four doses of a
comparator vaccine (control group).
In children who received 3 doses of RTS,S/AS01 plus a booster, the
number of clinical episodes of malaria at 4 years was reduced by just
over a third (36%). This is a drop in efficacy from the 50% protection
against malaria seen in the first year.
Importantly, without a booster dose, significant efficacy against
severe malaria was not shown in this age group. However, in children
given a booster dose, overall protective efficacy against severe malaria
was 32%, and 35% against malaria-associated hospitalisations.
In infants who received 3 doses of RTS,S/AS01 plus a booster, the
vaccine reduced the risk of clinical episodes of malaria by 26% over 3
years follow-up. There was no significant protection against severe
disease in infants.
Meningitis occurred more frequently in children given RTS,S/AS01 (11
children in the group who received the booster dose and 10 in those who
did not) than in those given the control vaccine (1 child). RTS,S/AS02
produced more adverse reactions than the control vaccines. Convulsions
following vaccination, although uncommon, occurred more frequently in
children who received RTS,S/AS01 than in controls. The incidence of
other serious adverse events was similar in all groups of participants.
According to Professor Greenwood, "The European Medicines Agency
(EMA) will assess the quality, safety, and efficacy of the vaccine based
on these final data. If the EMA gives a favorable opinion, WHO could
recommend the use of RTS,S/AS01 as early as October this year. If
licensed, RTS,S/AS01 would be the first licensed human vaccine against a
parasitic disease."
Writing in a linked Comment, Vasee Moorthy and Jean Marie Okwo-Bele,
from the Department of Immunization, Vaccines and Biologicals at WHO in
Geneva, Switzerland say, "The donor community would need to coordinate
any financing for the RTS,S/AS01 vaccine carefully, should it reach that
stage. In particular, funding must not be redirected away from meeting
adequate access to artemisinin-combination treatments, rapid diagnostic
tests, longlasting insecticidal nets, and other malaria control measures
already in place in certain settings."
Journal Reference:
- RTS,S Clinical Trials Partnership. Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial. The Lancet, 2015 DOI: 10.1016/S0140-6736(15)60721-8
Courtesy: ScienceDaily
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