TECHBRIEF

HORIZON SCANNING REPORT

Malaria Vaccine
Report No: 003/2017

MaHTAS
Medical Development Division
Ministry of Health, Malaysia
2017
Prepared by:

Dr. Syaharatul Patimah Kamarudin

Medical Officer
Principal Assistant Director
Health Technology Assessment Section (MaHTAS)
Medical Development Division
Ministry of Health Malaysia

Reviewed by:

Dr. Izzuna Mudla Mohamed Ghazali

Public Health Physician
Senior Principal Assistant Director
Health Technology Assessment Section (MaHTAS)
Ministry of Health Malaysia

Dr. Junainah Sabirin

Public Health Physician
Deputy Director
Health Technology Assessment Section (MaHTAS)
Medical Development Division
Ministry of Health Malaysia

Disclosure: The author of this report has

no competing interest in this subject and
the preparation of this report is totally
funded by the Ministry of Health,
Malaysia.

Disclaimer: TechBrief report is prepared

based on information available at the time
of research and a limited literature. It is
not a definitive statement on the safety,
effectiveness or cost-effectiveness of the
health technology covered. Additionally,
other relevant scientific findings may have
been reported since completion of this
report.

Horizon Scanning, Communication &

Information Unit, MaHTAS,
Medical Development Division,
Ministry of Health, Malaysia,
Email: htamalaysia@moh.gov.my
Web: http://www.moh.gov.my

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 HS08

TechBrief

MALARIA VACCINE
SUMMARY people (new cases) and caused an
estimated 429 000 deaths. The disease
RTS,S/AS01 and PfSPZ are two malaria is a major burden in an African region
vaccine candidates which target pre- that contributes to more than 90% of
erythrocytic stage of parasite. They only cases and death.1
protect against Plasmodium falciparum
infection, but different strains of malaria Although Malaysia is in the pre-
are of high importance in Malaysia. elimination phase, the number of
indigenous cases increased from 2921
Less than half of the children may be
in 2013 to 3147 in 2014, and the
protected against clinical malaria with
number of people living in active foci
RTS,S/AS01, but the efficacy became
remains high (1.3 million). Malaria
much lower in infants. The occurrence
transmission occurs primarily in the
of serious adverse events of meningitis
districts of Sabah and Sarawak and in
during trial warrants further study to
some remote areas in Selangor,
investigate the causality. PfSPZ gave
Pahang, Kelantan and Perak.1,2
modest protection by time to first
infection in adults. Only minimal local
In 2012, 61.6% of reported cases were
and systemic adverse events were
human malaria infection and significant
reported.
proportions (38.4%) were zoonotic
(Plasmodium knowlesi). Among human
There could be potential for the
malaria infection, Plasmodium vivax
vaccines to give false sense of security
accounted for 50.2%, followed by
to the population and lead to reduction
Plasmodium falciparum (30.7%),
in the use of other preventive measures
Plasmodium malariae (16.7%) and
such as insecticide treated bed net.
mixed infection (2.2%).2
Whereas the vaccines are intended only
as an addition to the existing measures.
Children below the age of five
accounted for small proportion (2.5%) of
Keywords: RTS,S/AS01, PfSPZ,
all cases. About 61.9% of the cases
malaria vaccine, horizon
were between the ages of 20 to 49
scanning,Plasmodium falciparum
years.2
Plasmodium knowlesi infection has
INTRODUCTION
increasingly becoming public health
Malaria is a mosquito borne disease importance in Malaysia owing to its
caused by Plasmodium genus parasites rapid and severe clinical course which
transmitted by Anopheles mosquitoes. contributes to high fatality.3
Globally, malaria infected 212 million

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Various approaches has been effective, the vaccine must be safe, well
implemented to control and if possible to tolerated, offer the expected protection
eliminate malaria. However, the disease against various types of malaria and
is still prevalent. Vaccination is seen as feasible for mass vaccination
one of the possible approach in addition programme. 7

to the existing measures. Despite vast

number of researches done (Table 1), Hence, the objective of this early
there is still no single licensed malaria assessment is to evaluate the efficacy,
vaccine for use to date.4,5,6 tolerability and safety profile of these
two malaria vaccine candidates against
Table 1: The main malaria vaccines that are
currently undergoing clinical trials phase 2b malaria.
and phase 3
THE TECHNOLOGY
Vaccines Trial Funder
Pre-erythrocytic Projects RTS,S/AS01 (MOSQUIRIX) MALARIA
RTS,S/ Phase PATH - Malaria Vaccine VACCINE4
AS01E 3 Initiative (MVI)

National Institute of Until now, RTS,S/AS01 (Mosquirix) is

Phase Allergy and Infectious the only malaria vaccine candidate
PfSPZ
2b Diseases (NIAID (US
NIH)) which reaches phase 3 trials. This
European and vaccine candidate has been developed
ChAd63/MV Phase Developing Countries over three decades through a
A ME-TRAP 2b Clinical Trials
Partnership (EDCTP) partnership between GlaxoSmithKline
Blood-stage Projects
Biologicals (GSK) and the PATH Malaria
Vaccine Initiative (MVI) with funding
European and
Developing Countries support from the Bill & Melinda Gates
Clinical Trials Foundation.
Phase Partnership (EDCTP),
GMZ2 field
2b African Malaria Network
Trust (AMANET), It is a recombinant vaccine in which
European Vaccine regions of Plasmodium falciparum
Initiative (EVI)
circumsporozoite protein are fused to
African Malaria Network hepatitis B surface antigen and
Trust (AMANET),
MSP3 [181- Phase European and adjuvanted with AS01 to enhance
276] field 2b Developing Countries
immune response (Figure 1). The
Clinical Trials
Partnership (EDCTP) preparation available is as a 25 µg
powder and solvent for suspension for
The RTS,S/AS01 is the most advance injection in vials.
malaria vaccine candidate in
This vaccine targets the pre-erythrocytic
development which already reached
stage of the malaria parasite by
phase 3 clinical trial. Another vaccine
production of anti-circumsporozoite
candidate PfSPZ gains much attention
antibodies that attack the parasite
after showing a breakthrough results in
before it can invade human liver.
its recent phase 2 trial. In general, to be

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 PfSPZ MALARIA VACCINE

PfSPZ malaria vaccine candidate is

developed by Sanaria Inc., a
biotechnology company located in
Rockville, Maryland. The vaccine is
made up of non-replicating irradiated
whole sporozoites (aseptic, purified,
Figure 1: RTS,S recombinant protein virus- radiation- attenuated, cryopreserved
like particle (Source: European Medical
Agency) Plasmodium falciparum
sporozoites). 11,12

The sporozoites were collected by

In addition, it also provokes a strong
manually dissecting the mosquitos’
CD4 T-cell response, which can kill the
salivary glands, and then irradiate and
parasite in the liver before it can break
freeze the sporozoites for vaccination.
out into the blood stream subsequently
to invade red blood cells.
PfSPZ is still in the early stage of
RTS,S/AS01 is only effective against development but already showed
malaria caused by Plasmodium positive result from its early clinical
falciparum parasite. Hence, it offers no trials. Based on this, PfSPZ has
protection against other types of malaria received U.S. Food and Drug
including Plasmodium vivax which Administration Fast Track designation in
predominates in Malaysia. September 2016 to help expedite the
development process of the vaccine to
The European Medical Agency gave reach market.13
positive scientific opinion based on the
favourable quality and risk/benefit profile
of this vaccine from a regulatory
perspective on the 23 July 2015.4,8,9 In
October 2015, WHO recommends
conducting a pilot implementation
studies in three to five sub-Saharan
countries with moderate to high levels of
malaria transmission to generate more Figure 2: Direct venous inoculation of PfSPZ.
concrete evidence on protection level, (Source: B. Mordmueller)
safety profile and feasibility of
vaccination. 10 The most effective route of
administration is via intravenous
In addition, GSK is in the process of injection.12,14
planning phase 4 study to further
characterize the safety and
effectiveness of RTS,S/AS01 vaccine.

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 PATIENT GROUP AND EFFICACY AND SAFETY
INDICATION RTS,S/AS01 (MOSQUIRIX) MALARIA
VACCINE
Active immunisation against malaria
infection (Plasmodium falciparum), in A phase 3 randomised clinical trials has
children aged six weeks to 17 months been conducted in seven sub-Saharan
for RTS,S/AS01 malaria vaccine African countries to assess the efficacy
candidate. 15
and safety aspects of the vaccine.

Immunisation against Plasmodium From 2009 until 2011, the study enrolled
falciparum malaria infection for PfSPZ 8922 children (age five to 17 months)
vaccine. and 6537 young infants (age six to 12
weeks) in which each age group was
CURRENT PRACTICE randomly assigned into three groups,
namely R3R group (receive three doses
Various approaches are use
of vaccine at months 0,1 and 2 and a
simultaneously in order to control and
booster dose at month 20), R3C group
eliminate malaria. Preventive measures
(three doses of vaccine and a dose of
and medical treatment of the infection
comparator vaccine at month 20) and
both are important.
C3C group (receive comparator vaccine
WHO recommends the use of at months 0,1,2 and 20 [control group]).
Artemisinin Combination Therapy (ACT) The children group was followed up for
as the standard treatment for malaria. a median of 48 months after dose one
The treatment regimen use antimalarial and for 38 months for young infants
drugs such as riamet, artesunate, group. The occurrences of clinical and
mefloquine, primaquine, and quinine. severe malaria over 12 months after the
third dose were picked up via passive
Besides that, preventive measures case detection.16
consist of a combination of mosquito
avoidance measures and In another study, which was conducted
chemoprophylaxis. The mosquito as part of a phase 2 trial, Olutu A et al.
avoidance measures include insect evaluated the long term efficacy of
repellant, wearing long sleeves, long RTS,S/AS01 by following up the
pants, sleeping in a mosquito-free children aged five to 17 months at the
setting or using an insecticide-treated time of the first vaccination for seven
bed net. The use of diethyltoluamide years. Four hundred and fourty seven
(DEET) in lotions, spray, roll-on (447) children were recruited in Kifili,
formulation is safe and effective when Kenya and Korogwe, Tanzania and
applied to the skin of adults and were followed up from March 2007 until
children. November 2014 after they received
three doses of RTS,S/AS01. However,
only 312 children completed the follow

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up (164 children in the RTS,S/AS01 p=0.13) was observed in the fifth year.
group and 148 in the control group).17 Then, the efficacy dropped to 3.6%
(95% CI: -29.5, 28.2, p=0.81) in the
∑ EFFICACY seventh year which was not statistically
This study showed that RTS,S/AS01 significant.17
gave low protection against malaria (see In children, RTS,S/AS01 with booster
Appendix, Table 2 and 3). The best dose had averted more clinical malaria,
protection was seen in the older children severe malaria cases and malaria
who received four doses of vaccine with hospital admission when compared with
a vaccine efficacy of 36.35% (95% CI: no booster (1774 versus 1363 cases, 19
31.8, 40.5), p value <0.0001 against versus 8 cases and 40 versus 26 cases
clinical malaria and significant protection per 1000 children, respectively) (see
32.2% (95% CI: 13.7, 46.9), p value Appendix, Table 5). While in infants, this
0.0009 against severe malaria.16 vaccine averted 983 clinical malaria
The efficacy dropped to 25.9% (95% CI: cases in those who received booster
19.9, 31.5), p value <0.0001 in infants compared with those without booster
group who received four doses of dose only 558 cases averted per 1000
vaccine. Infants and young children who infants.16
did not receive the booster dose had an In the seven year follow up study, they
even lower vaccine efficacy against reported not statistically significant (317
clinical malaria, 18.3%, and 28.3% cases [95% CI -357; 973]) cases of
respectively. In infants, no significant clinical malaria averted per 1000
efficacy was noted against severe children who received RTS,S/AS01.17
malaria, with or without a fourth dose.16
SAFETY
From the study, the efficacy of the
primary vaccination reduced over time. Meningitis cases were reported to be
However, administration of booster dose higher in children who received the
gave longer protection against clinical RTS,S/AS01 when compared with
malaria in both age groups although the control group (11 in R3R group, ten in
protection was lower in infants group R3C group and one in C3C group).
compared with older children (see However, there was no significant
Appendix, Table 4).16 different in meningitis cases seen in
infants groups (five cases in the R3R
Olutu A et al. found a similar finding in group, seven in the R3C group, and six
children group who received primary in the C3C group). Hence, from this trial
vaccination and followed up for seven the researchers were unable to
years . In the first year after vaccination, conclude any association of the vaccine
RTS,S/AS01 gave low protection of with occurrence of meningitis.16
35.9% vaccine efficacy (95% CI: 8.1,
55.3, p=0.02). However, negative
efficacy of -27.6 (95% CI: -74.8, 6.8,

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On the other hand, no cases of in subjects who received higher dose of
meningitis were reported in a study by PfSPZ. (at least 5.12 x 104 PfSPZ). The
Olutu et al.17 range of follow up was three to 59
weeks.14,19,20,21,22
There were higher incidence of
generalised convulsive seizures within The first field trial of this vaccine was
seven days post vaccination with conducted by Sissoko et al. in Mali in 93
RTS,S/AS01 booster dose in both non-malaria naived adults. The double
children and infants when compared blind, randomised placebo controlled
with those who received control vaccine phase 1 trial aimed to assess the safety,
(in children, the incidence were 2.5 per tolerability, as well as efficacy of the
1000 doses in R3R group, 1.2 per 1000 vaccine against naturally acquired
doses in the R3C group and 0.4 per Plasmodium falciparum malaria.23
1000 doses in the C3C group; whereas
in infants the incidence were 2.2 per The vaccine group received five doses
1000 doses in the R3R group, 0.0 per of 2.7 x 105 PfSPZ while normal saline
1000 doses in the R3C group and 0.5 was given to the control group and was
per 1000 doses in the C3C group).16 followed up for six months. Sixty six
percent (27 of 41 participants) in the
The frequency of serious adverse vaccine group and 93% (37 of 40
events reported was almost similar participants) in the placebo group were
between the vaccine and the control infected with Plasmodium falciparum
group.16,17 malaria.23 The vaccine gave 48.3%
(95% CI: 14.5, 68.7) efficacy by time to
PfSPZ VACCINE first infection analysis and gave 28.8%
(95% CI: 8.2, 47.2) when measured
∑ EFFICACY AND SAFETY
against all infections. 23,24
This vaccine is still in the early stage of
The safety and tolerability of PfSPZ
development. Numerous completed and
vaccine has been proven good with
on-going phase 1 and 2 clinical trials
minimal local or systemic events
were conducted in United States of
reported.20,23
America, Germany and several African
countries in healthy volunteers from However, the optimal vaccine doses and
various age categories.18 regime has yet to be established.
In earlier studies, the vaccine efficacy A phase 1 study is ongoing in Equatorial
showed to be dose dependent. These Guinea and is estimated to be
studies involved healthy malaria-naive completed in August 2017. This study
volunteers who subjected to different participants involves healthy adults,
doses, regimens and length of follow up, adolescents, children and infants.25
and subsequently underwent controlled
human malaria infection. The efficacies While in western Kenya, the phase 1
were higher, which were more than 55% and 2 trial recruits healthy children and

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infants aged 5 months to 9 years and inoculation.20,22,23 Hence, the practicality
approximated to complete in December of repeated venous injection especially
2018.26 in infants and children need to be
considered further.23
ESTIMATED COST
The logistic concern rises in view of this
RTS,S/AS01 (MOSQUIRIX) MALARIA vaccine which requires liquid nitrogen
VACCINE for storage and transport. Thus, a
reliable liquid nitrogen cold chain logistic
The exact price of RTS,S/SAS01
is necessary.23
vaccine is not yet finalised.4 Despite
that, the RTS,S/SAS01 vaccine is Furthermore, manually dissecting the
anticipated to be priced around USD5 mosquito’s salivary gland to harvest the
(±RM 21.64) per unit. The estimated sporozoites is a slow and tedious
cost is about USD20 (±RM 86.55) per process that seems impossible for mass
regimen which includes three doses scale production. In order to overcome
plus a booster, excluding a delivery this, Sanaria Inc. is working on
cost.27 Sporobot, a robot dissecting the
mosquito to automate the sporozoites
There was no information retrieved on
collecting process.28
cost for PfSPZ vaccine.

*(USD 1 = RM 4.33) POTENTIAL IMPACT

Both RTS,S/AS01 and PfSPZ malaria
ORGANIZATIONAL ISSUES
vaccine candidates showed promising
RTS,S/AS01 (MOSQUIRIX) MALARIA results.
VACCINE
Although RTS,S/AS01 vaccine is
The study showed that the vaccine leading the race, nonetheless it still has
needs to be given in full four doses to be issues of low vaccine protection and
effective. Hence, there will be a serious adverse effects that one should
challenge to ensure the children get the look into before it can go further into
full course of vaccination. If adoption of mass vaccination programme.
this vaccine is a must, it is preferable to
include this vaccine in national Less than half of the children may be
vaccination programme specifically for protected against clinical malaria with
children living in malaria endemic area. RTS,S/AS01, but the efficacy became
much lower in infants. From the study,
PfSPZ VACCINE
the efficacy waned over time in which
The regime for PfSPZ has not yet been the RTS,S/AS01 vaccination may need
optimised. In the early trials, this vaccine to be repeated in another four years’
was given either in three, four or five time.16,17
doses via direct venous

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Both vaccines were only shown to 3. Sabbatani S, Fiorino S & Manfredi R.
protect against Plasmodium falciparum The Emerging of the Fifth Malaria
infection, but different strain of malaria Parasite (Plasmodium knowlesi). A
namely, Plasmodium vivax and Public Health Concern? Braz J Infect
Plasmodium knowlesi are of high Dis. 2010;14(3):299-309.
importance in Malaysia.
4. Fact sheet: RTS,S malaria vaccine
The need for full course of four doses of candidate (Mosquirix™). Malaria
RTS,S/AS01 to confer immunity and the Vaccine Initiative. Available at
route of administration via direct venous http://www.malariavaccine.org/sites/
inoculation for PfSPZ in multiple doses www.malariavaccine.org/files/content
may influence the feasibility and /page/files/RTSS%20vaccine%20ca
compliance towards the vaccines. ndidate%20Factsheet_FINAL.pdf.
Accessed on 8 February 2017.
The occurrence of serious adverse 5. Arama C & Troye-Blomberg M. The
events such as meningitis post Path of Malaria Vaccine
RTS,S/AS01 vaccination warrants Development: Challenges and
further study to investigate the causality. Perspectives. J Intern Med.
2014;275(5):456-66.
Furthermore, there could be potential for
the vaccines to give false sense of 6. Tables of Malaria Vaccine Projects
security to the population and lead to Globally. Immunization, Vaccines
reduction in the use of other preventive and Biologicals. World Health
measures such as insecticide treated Organization. Available at
bed net. Whereas, the vaccines are http://www.int/immunization/research
intended only as an addition to the /development/Rainbow_tables/en/.
existing measures. Accessed on 4 April 2017.

REFERENCES 7. Epstein JE & Richie TL. The Whole

Parasite, Pre-erythrocytic Stage
1. Fact Sheet: World Malaria Report Approach to Malaria Vaccine
2016. Malaria. World Health Development: A Review. Curr Opin
Organisation. Available at Infect Dis. 2013 Oct;26(5):420-428.
http://www.who.int/malaria/media/wo
8. First Malaria Vaccine Receives
rld-malaria-report-2016/en/.
Positive Scientific Opinion from
Accessed on 8 February 2017.
EMA. Press Release. European
2. Management Guidelines of Malaria Medicines Agency. 24 July 2015.
in Malaysia. Vector Borne Disease Available at
Sector. Disease Control Division. http://www.ema.europa.eu/docs/en_
Ministry of Health Malaysia. 2014. GB/document_library/Press_release/
2015/07/WC500190447.pdf.
Accessed on 4 April 2017.

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9. MosquirixTM. Assessment Report. Nonreplicating Sporozoite Vaccine.
European Medicines Agency. 23 July Science. 2013;341(6152):1359-65.
2015. Available at
www.ema.europa.eu/docs/en_GB/do 15. Mosquirix. Summary of Opinion
cuments_lirary/Medicine_for_use_ou Committee for Medicinal Products for
tside_EU/2015/10/WC500194577.pd Human Use. European Medicines
f. Accessed on 4 April 2017. Agency. 23 July 2015.
EMA/CHMP/464758/2015. Available
10. Pilot Implementation of First Malaria at http://www.ema.europa.eu/docs/
Vaccine Recommended by WHO en_GB/document_library/Medicine_f
Advisory Group. News Release. or_use_outside_EU/2015/07/WC500
Media Centre. World Health 190452.pdf. Accessed on 23
Organization. 23 October 2015. February 2017.
Available at
http://www.who.int/mediacentre/new 16. RTS,S Clinical Trials Partnership.
s/releases/2015/sage/en/. Accessed Efficacy and Safety of RTS,S/AS01
on 28 February 2017. Malaria Vaccine with or without a
Booster dose in Infants and Children
11. Sanaria - Malaria Eradication in Africa: Final Results of a Phase 3,
Through Vaccination. Available at Individually Randomised, Controlled
http://www.sanaria.com/index.php?s Trial. The Lancet.
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12. Schayk IV. Progress with Sanaria’s 17. Olutu A, Fegan G, Wambua J et al.
Plasmodium falciparum sporozoite Seven Year Efficacy of RTS,S/AS01
vaccines. Malaria World. March Malaria Vaccine among Young
2017. Available at African Children. N Engl J Med.
https://malariaworld.org/blog/progres 2016;374(26):2519-2529.
s-sanaria%E2%80%99s-plasmodium
-falciparum-sporozoite-vaccines. 18. Phase 2 Trial Of Radiation-
Accessed on 10 April 2017. Attenuated Malaria Vaccine Debuts
in Kenya. The Foundation for
13. Sanaria PfSPZ Vaccina Against vaccine Research. January 2017.
Malaraia Receives FDA Fast tract Available at http://www.vaccine
Designation. Available at foundation.org/. Accessed on 3 May
http://www.sanaria.com/pdf/Fast%20 2017.
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SEP2016.pdf. Accessed on 12 April 19. Epstein JE, Paolino KM, Richie TL et
2017. al. Protection Against Plasmodium
Malaria by PfSPZ Vaccine. JCI
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21. Lyke KE, Ishizuka AS, Berry AA et
al. Attenuated PfSPZ Vaccine 26. Safety, Tolerability and Efficacy of
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22. Ishizuka AS, Lyke KE, DeZure A et 2017.
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25. Safety, Tolerability and

Immunogenicity of PfSPZ Vaccine in

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Appendix

Table 2: Vaccine efficacy against clinical malaria

Number of clinical Vaccine efficacy (95% CI), p value

malaria episodes
C3C R3C R3R R3C vs C3C R3R vs C3C
Children group (age five to 17 months)
Month 0 to
9585 7396 6616 28.3% (23.3,32.9), <0.0001 36.35% (31.8,40.5), <0.0001
study end
Young infants group (age six to 12 weeks)
Month 0 to
6170 5444 4993 18.3% (11.7,24.4), <0.0001 25.9% (19.9,31.5), <0.0001
study end
C3C = control group, R3C = primary vaccine without booster group, R3R = primary vaccine plus booster group.
Vaccine efficacy = 1 – relative risk for clinical malaria.

Table 3: Vaccine efficacy against severe malaria

Number of participants with at least Vaccine efficacy (95% CI), p value

one episodes of severe malaria
C3C R3C R3R R3C vs C3C R3R vs C3C
Children group (age 5 to 17 months)
Month 0 to
171 169 116 1.1% (-23.0, 20.5), 0.96 32.2% (13.7, 46.9), 0.0009
study end
Young infants group (age 6 to 12 weeks)
Month 0 to
116 104 96 10.3% (-17.3, 31.8),0.45 17.3% (-9.4, 37.5), 0.16
study end
C3C = control group, R3C = primary vaccine without booster group, R3R = primary vaccine plus booster group.
Vaccine efficacy = 1 – relative risk for severe malaria.

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Table 4: Incremental vaccine efficacy after booster dose against clinical malaria

Incremental vaccine efficacy

Vaccine efficacy (95% CI)
(during 12 months after booster
(month 33 to study end)
vaccination)
R3C vs C3C R3R vs C3C R3R
Children group (age 5 to 17 months)
2.9% (-6.4, 11.4) 12.3% (3.6, 20.1) 25.6% (18.2, 32.3)

Young infants group (age 6 to 12 weeks)

4.4% (-6.7, 14.3) 10.5% (0.2, 19.7) 22.3% (14.0, 29.8)
C3C = control group, R3C = primary vaccine without booster group, R3R = primary vaccine plus booster group.
Incremental efficacy = 1 – (incident rate ratio between the R3R and R3C groups).

Table 5: Number of cases averted per 1000 participants

Number of cases averted per 1000 participants (95% CI)

(from month 0 to study end)
Type of cases Children group Young infants group
(age 5 to 17 months) (age 6 to 12 weeks)
R3C R3R R3C R3R
Clinical malaria 1363 (995, 1797) 1774 (1387, 2186) 558 (158, 926) 983 (592, 1337)

Severe malaria 8 (-9, 26) 19 (4, 35) 8 (-13, 28) 12 (-6, 32)
Malaria hospital
26 (4, 51) 40 (19, 64) 14 (-13, 39) 18 (-8, 42)
admission
C3C = control group, R3C = primary vaccine without booster group, R3R = primary vaccine plus booster group.

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