Ifakara Health Institute, (IHI)

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Spotlight
November, 2012          Issue 14
   
   Key Points
TB is a major burden in Tanzania and other 
African countries
Existing TB vaccines are not effective in 
preventing TB in adults
Alternative vaccine candidates are under 
development
Among these, the H1/IC31 candidate vaccine 
is being tested and IHI is among institutions 
involved in this research
Phase II of the study is currently ongoing in 
Bagamoyo
Introduction
In 2010, tuberculosis (TB) infected 8.8 million people of 
whom almost one in five died.  TB is caused by various 
strains of Mycobacterium tuberculosis bacteria, is spread 
from person to person through the air. 
TB deaths occur predominantly in poor countries. 
Tanzania is among the top 22 high-burden countries, 
which collectively account for about 80% of global TB 
cases. TB tends to affect mostly young adults, in their 
most productive years. 
In 2010, the incidence of TB in Tanzania was estimated 
to be as high as 281 infected people for every 100,000 
Tanzanians, according to WHO data and the disease 
killed 13 for every 100,000 Tanzanians in 2010.  At least 
12 people die of TB each day in Tanzania.  Although 
prevalence of TB has been declining (see Figure 1 below), 
TB remains a major burden for Tanzania. 
Multi-drug resistant TB (MDR-TB), a main threat to TB 
control, accounted for an estimated 1.1% of new TB cases 
in Tanzania, in 2010.  
Figure 1: Case notification and estimated TB incidence rate
Trends in case notification rates (new and relapse cas-
es, all forms) (black) and estimated TB incidence rates 
(green). Shaded areas  represent uncertainty bands. 
Source: WHO, Global tuberculosis report 2012. 
There is thus a growing impetus to improve existing TB 
vaccines and devise new and more effective ones.  The 
only licensed TB vaccine, the Bacille Calmette Guerin (BCG) 
is very effective against severe and disseminated forms 
of TB among children.  However, because BCG-induced 
protection wanes within a decade, its efficacy among 
adults is variable.  The Ifakara Health Institute (IHI) is 
among the global partners in this search for an effective 
TB vaccine.  This Spotlight discusses alternative TB vaccine 
candidates and specifically highlights IHI’s involvement 
in this work.
BCG
The BCG vaccine was developed between 1906 and 1919 
by Boquet, Calmette, and Guérin, hence the name.  The 
vaccine is a live, but weakened form of the bacteria that 
causes TB, and works by stimulating the body’s defense 
mechanisms against the bacteria.  BCG has recorded more 
than 4 billion safe administrations at a cost of US $0.1 - US 
$0.2 per dose of product.  Given to over 90% of children 
today, BCG is the most widely-used vaccine in the world.   
The vaccine protects against severe forms of tuberculosis 
in newborns and young children. However, the present 
regimen of BCG vaccination has little or no effect when 
administered to adults. This has lead towards a push to 
search for alternatives.  
Search for a 
New TB Vaccine
research | training | services2
Spotlight Issue 14 November, 2012
research | training | services
Alternatives to BCG
New vaccine candidates need to induce a more efficient 
immunity than that achieved by BCG.  What is needed is a new 
vaccine which targets and contains TB bacteria and prevents 
reactivation of the disease at some later stage.  Current global 
vaccination strategies being tested involve vaccination with 
a viable vaccine, that either “boosts” the immune system’s 
ability to neutralize TB bacteria or as replacement for BCG.   
Present vaccination candidates only reduce the initial amount 
of TB bacteria in one’s body.  The rest of the TB bacteria are 
simply contained (see Figure 2 below).
The underlying mechanism of action of present vaccine 
candidates is to stimulate the body’s immune system’s 
capabilities to fight TB bacteria.  There are many types 
of vaccines currently under development. These include 
live mycobacterial vaccines, DNA-based vaccines and 
subunit vaccines.  
Living mycobacterial vaccines pose significant health 
risks in HIV-infected individuals. Although this can be 
addressed, significant regulatory barriers imposed on 
genetically modified organisms have impeded efficient 
development of these vaccines.  DNA vaccines have so 
far been disappointing in stimulating the body’s immune 
response and protection in model studies. Not surprisingly, 
then, three of the most advanced vaccines are all subunit 
vaccines. 
Figure 2: Different Vaccination Strategies (Source: Kaufmann, et al., 2010)
Present strategy: (A) pre-
exposure vaccination with BCG 
protects against early childhood 
tuberculosis but does not eradicate 
Mycobacterium tuberculosis. 
Future vaccination strategies: (B) 
pre-exposure boost with subunit 
vaccine in children primed with 
BCG to prevent tuberculosis in early 
childhood and to delay tuberculosis 
disease outbreak in adults; (C) post-
exposure boost with subunit vaccine 
in adults who had been primed 
with BCG during early childhood 
to delay tuberculosis disease 
outbreak in adults;  D) pre-exposure 
vaccination with superior BCG 
replacement to prevent tuberculosis 
in early childhood and to delay 
tuberculosis disease outbreak in 
adults; (E) therapeutic vaccination 
in adjunct to chemotherapy in 
patients with active tuberculosis; 
(F) heterologous prime-boost 
vaccination with superior BCG 
replacement and subunit vaccine, 
to achieve sterile eradication; 
(G) heterologous prime-boost 
vaccination in individuals with 
latent infection by prime with 
superior BCG replacement and 
subunit vaccine boost to prevent 
tuberculosis disease outbreak; 
and (H) pre-exposure vaccination 
to prevent stable infection with M 
tuberculosis.3
Spotlight Issue 14 November, 2012
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Subunit vaccines 
These vaccines work by improving our bodies’ ability to 
identify and neutralize TB bacteria. Subunit vaccine approach 
builds on the concept of stimulating the immune response 
to a number of selected antigens delivered in the form of 
recombinant antigens.  The Statens Serum Institut (SSI) 
in Denmark has duplicated and evaluated 250 of these 
antigens from TB bacteria.  They have selected a few, most 
promising, in stimulating the body’s immune response against 
TB bacteria.  Some of these antigens have demonstrated 
protective efficacy in animals.  
These efforts constitute, among the most prominent 
vaccine candidates, the HI/IC31 candidate vaccine (a 
combination of SSI’s Ag85B-ESAT-6 and Intercell’s 
IC31®).   The H1/IC31® candidate vaccine enhances the 
recipient’s immune response.  It is among the most 
promising for low-income settings and is safe for HIV-
infected individuals.  See an overview of candidates in 
Figure 3 below.
Figure 3: Vaccine Candidates in Clinical Trials, Globally (Source: Kaufmann, et al., 2010)Spotlight Issue 14 November, 2012
Ifakara Health Institute. Plot 463, Kiko Avenue, Mikocheni.  P.O. Box 78373, Dar es Salaam, Tanzania.
Web: www.ihi.or.tz ; E-mail address: info@ihi.or.tz Phone: +255 (0)22 2774756 Fax: +255 (0)22 2771714
Hope for the future
Given that TB killed as many as 6900 Tanzanians in 2010 
alone, all hopes hinge on the success of global efforts to 
find an effective alternative TB vaccine.  IHI is conducting 
the first randomized, double-blind, clinical phase II trial 
evaluating the H1/IC31 vaccine candidate’s ability to 
enhance the body’s immune response against TB bacteria 
and safety of two doses of the vaccine, in HIV-positive 
individuals.  The trial is conducted in collaboration with 
SSI, Aurum Institute, Swiss Tropical and Public Health 
Institute, and the South African TB Vaccine Initiative.  Dr. 
Klaus Reither leads IHI’s efforts in the H1/IC31 TB vaccine 
candidate study in Bagamoyo working together with 
Elirehema Mfinanga, Humphrey Shao, and Khadija Said. 
Their work is still ongoing.  IHI hopes to continue along 
this line of work in collaboration with other institutions.   
References
Calmette, A., Guérin, C., Boquet, A. & Négre, L., 1927. 
Prophylactic vaccination against tuberculosis using 
“BCG”. 
The Guardian, S., 2011. Tanzania’s continous battle 
with TB burden. (Online)  
Available at: http://www.ippmedia.com/frontend/in-
dex.php?l=27696 
(Accessed 9 July 2012).
Irikefe, V. et al., 2011. The View from the Front Line: 
Africa’s nations are achieving some success in build-
ing their science capacity, but the foundations remain 
unsteady. Nature, 30 June, Volume 474, pp. 556-559.
Kaufmann, S., Hussey, G. & Lambert, P., 2010. New 
vaccines against tuberculosis. Lancet, Volume 375, pp. 
2110-19.
Kumar, V., Abbas, A., Fausto, N. & RN, M., 2007. Rob-
bins Basic Pathology. 8th ed. s.l.:Saunders Elsevier.
Lambert, P., Hawkridge, T. & Hanekom, W., 2009. New 
vaccines against tuberculosis. Clin Chest Med, Volume 
30, pp. 811-26.
Lawn, S. D. & Zumla, A. I., 2011. Tuberculosis. Lancet, 
Volume 378, pp. 57-72.
Trunz, B., Fine, P. & Dye, C., 2006. Effect of BCG vaccina-
tion on childhood tuberculosis meningitis and miliary 
tuberculosis worldwide: a meta-analysis and assess-
ment of cost-effectiveness. Lancet, Volume 367, pp. 
1173-80.
WHO, 2012. WHO Media Centre. (Online)  
Available at: http://www.who.int/mediacentre/fact-
sheets/fs104/en/index.html 
(Accessed 9 July 2012).
WHO, 2012. WHO TB Country Profile: United Republic 
of Tanzania. (Online).  
Available at: https://extranet.who.int/sree/
Reports?op=Replet&name=/WHO_HQ_Reports/G2/
PROD/EXT/TBCountryProfile&ISO2=tz&outtype=pdf 
(Accessed 9 July 2012).

Effect of BCG vaccination on childhood tuberculosis meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness.

New vaccines against tuberculosis.

Prophylactic vaccination against tuberculosis using “BCG”.

Tanzania’s continous battle with TB burden.

The View from the Front Line: Africa’s nations are achieving some success in building their science capacity, but the foundations remain unsteady.

WHO Media Centre. (Online) Available at:

WHO TB Country Profile: United Republic of Tanzania.

Search for a New TB Vaccine

http://ihi.eprints.org/1799/1/Sportlight_issue_%2D14_final.pdf

Search for a New TB Vaccine

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