Type of Review: Project Completion Review
Project Title: International AIDS Vaccine Initiative (IAVI)
Date started: 16 January 2009
Date review undertaken: 19 April 2013
Instructions to help complete this template:
Before commencing the review you should have to hand:
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the Business Case or earlier project documentation.
the Logframe
the detailed guidance (How to Note) - Reviewing and Scoring Projects,
the most recent annual review and other related monitoring reports.
key data from ARIES, including the risk rating
the separate project scoring calculation sheet (pending access to ARIES)
Two scores are produced at project completion - one based on achievement of the outputs and
one based on achievement of the outcome. You should assess and rate both the individual
outputs and the overall outcome using the following rating scale and description:
Output Description
Outputs substantially exceeded expectation
Outputs moderately exceeded expectation
Outputs met expectation
Outputs moderately did not meet expectation
Outputs substantially did not meet expectation
Scale
A++
A+
A
B
C
Outcome Description
Outcome substantially exceeded expectation
Outcome moderately exceeded expectation
Outcome met expectation
Outcome moderately did not meet expectation
Outcome substantially did not meet
expectation
Introduction and Context
What support did the UK provide?
DFID provided £40 million over five financial years (2008/2009 to 2012/2013) to advance the
development of safe, effective, accessible, preventive HIV vaccines for use throughout the
world.
What were the expected results?
IAVI’s goal is to develop effective HIV vaccines that are affordable, available and adopted
worldwide, and so to reduce death and illness from HIV and AIDS.
Over the five-year grant period, IAVI aimed to identify and advance the most promising and
innovative approaches to vaccine design and development; rigorously prioritise candidate
vaccines based on data from systematic and comparative studies; obtain clinical data from
populations at risk of HIV quickly without compromising safety; and ensure a supportive
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environment for both research and rapid access to a successful vaccine through global
advocacy and policy efforts.
The major milestones that were expected over the five-year grant period were:
•
Elicit HIV neutralising antibodies by advancing one or more candidates to Phase I clinical
trials that elicits broadly neutralizing antibodies;
•
Controlling HIV replication by advancing one or more candidates to Phase I clinical trials
that more effectively controls HIV than any current candidate in development
•
Improving the clinical pipeline of AIDS vaccine candidates by advancing at least one
candidate through ethical and regulatory approvals, and Phase I and Phase II trials to a
Screening Test of Concept (STOC) trial in the next five years, which obtains efficacy data
from fewer volunteers in a shorter timeframe and at lower cost
•
Bring innovation to all aspects of AIDS vaccine effort by recruiting novel technology from
biotech and academia to AIDS vaccine design and development and create incentives
for their use; advocate and identify incentives or other mechanisms that stimulate
innovation in AIDS vaccine discovery R&D
•
Ensure adequate and appropriate clinical research and trial capacity to the highest
ethical and regulatory standards to inform vaccine design and assessment and
accelerate clinical trials. To achieve this, IAVI aimed to establish a global network of
collaborating clinical trial centres with clinical and laboratory capability and infrastructure
linked to a network of collaborating scientists in the North and South and under the
auspices of the Human Core Immunology Laboratory (Imperial College, London) and the
Clinical Reference Laboratory (Johannesburg, SA) to ensure standardisation and quality
assurance and control.
•
Maintain political and financial commitment to NPTs and AIDS vaccine R&D, by ensuring
funding is matched to R&D needs in size, duration, predictability and flexibility through
analysis and advocacy efforts.
•
Ensure state of the art management and operations to support IAVI’s ability to work with
speed, flexibility, innovation and in partnership with stakeholders throughout the world.
IAVI aimed to achieve this through integrated management and operational systems to
address internal and external stakeholder needs in support of its mission
What was the context in which UK support was provided?
HIV and AIDS is a major cause of mortality and morbidity throughout the world and particularly
in Sub-Saharan Africa. There are over 34 million people living with HIV, more than 69% of
whom live in Sub-Saharan Africa and women are disproportionately affected. There is no cure
for AIDS - Antiretroviral (ARV) drugs suppress its symptoms but are expensive and associated
with serious side-effects. Despite the significant scale up in access to ARVs, there are 7
million people in need of treatment that are not receiving it and ARV drugs are still not
available to many people living with HIV/AIDS in developing countries. New HIV infections
continue to outpace treatment, placing increasing financial and institutional pressure on
governments and organisations committed to improving global health.
An effective vaccine is needed for HIV prevention to end the pandemic, and would result in
both much less human suffering and much lower costs, compared to treatment. Recent
modelling has shown that even a partially effective vaccine could significantly cut HIV infection
rates. The development of a viable vaccine to address HIV and AIDS would reduce the
economic, social and financial burden of this disease on the millions of poor people, and their
families, suffering from HIV/AIDS in developing countries. The complexities of the HIV virus,
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and in particular its ability to mutate, makes the development of an effective vaccine
scientifically very challenging.
At the start of this funding period in 2008, the only two vaccine candidates developed since the
identification of HIV had failed to show any evidence of effect in either preventing or controlling
HIV infection. Even more disappointingly, the second of these vaccines (Merck rAd5)
demonstrated a greater proportion of new infections in the vaccine arm of the trial vs. placebo.
During the funding period, there was more optimism about progress in HIV-vaccine research,
largely due to emerging opportunities to explore the potential of broadly neutralising antibodies
to HIV infection and replicating vectors – both areas of work in which IAVI has made important
contributions.
Section A: Detailed Output Scoring
Output 1: To implement an innovative Research & Development programme across the
whole pipeline, from vaccine development to clinical trials
Output 1: final score and performance description: A – outputs met expectations
Final results:
HIV vaccine research, by its very nature, is a complex and long-term endeavour. As research
advances, new and occasionally unpredictable avenues of research are opened and explored.
Successful candidates may stimulate further research in one direction, and failures may
demand a fundamental revision of existing understanding and halting particular research
areas. This on-going, iterative process cannot be segmented into discrete research
‘packages’ that can be predicted at the beginning of a grant period, nor concluded at a predefined time-point when the funding ends. The outputs reported here reflect this: there have
been many advances in a number of directions, with a variety of results, and IAVI’s research
efforts continue beyond the lifetime of this grant period.
During the grant period, IAVI and partners developed 16 vaccine candidates, prioritised ten for
further development and advanced seven to clinical trials primarily in Africa. Two candidates,
from IAVI’s broadly neutralising antibody (bNAb) and replicating viral vector programmes, will
enter clinical trials in 2013, with 2 more candidates from the vectors programme progressing
on a development path. This milestone toward an antibody-inducing vaccine was made
possible by the isolation and characterisation of dozens of new bNAbs that offer new tools for
immunogen design, and the important scientific breakthroughs by IAVI and partners in
understanding the structure of the virus and how bNAbs bind to HIV to block infection.
IAVI is focusing on two primary approaches to advancing a portfolio of preventative HIV
vaccine candidates:
1. Cell–mediated immunity, in which the body’s immune cells (T cells) work together to
destroy HIV infected cells
2. Broadly neutralising antibodies approach, whereby candidates engage the immune
system to generate antibodies that neutralise HIV infection and so prevent lasting
infection.
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Output Indicator 1- Number of pre-clinical vaccine candidates, immunogens, vaccine
vectors and work on cell mediated immunity in development to feed the early stages of
the pipeline
Immunogens
In 2012, IAVI worked to design, make and analyse (in vitro) immunogens to elicit bNAbs, and
screened 60 immunogens.
Two lead immunogen candidates (Wyatt JFRL Trimer Candidate; and Moore BG505 Trimer
Candidate) have been identified to advance to clinical development, and cell-line development
has been initiated to make Good Manufacturing Practice (GMP) product of both. The Wyatt
JFRL Trimer Candidate is a prime-boost combination regimen consisting of a DNA prime
encoding the Trimer+ and a protein Trimer boost - pre-clinical testing results are very
encouraging. The Moore BG505 Trimer is a stabilised HIV Env Trimer (termed BG505-SOSIP
Trimer).
There are plans to further advance at least 2 other bNAb eliciting candidates: the Expressing
Trimer on Carrier Virus candidate, which expresses the native HIV trimer on the surface of the
vesicular stomatitis virus (VSV). VSV is chemically inactivated which also serves to stabilise
the Trimer; the Schief eOD (external outer domain of HIV env trimer) candidate, which uses
structural information defined by the binding of broadly neutralising antibodies against HIV to
reverse engineer immunogens that can elicit such antibodies when used as a vaccine. This
nascent candidate is planned to enter preclinical immunogenicity studies in early 2013.
Cell-mediated immunity: Viral vector-based candidates
IAVI has developed four replicating viral vector-based vaccine candidates to control HIV
infection via cellular immunity:
1. Sendai-Virus vector-based candidate: This candidate has achieved final regulatory
approvals and started enrolment in phase 1 clinical trials in early 2013. It will assess
safety and immunogenicity alone and in combination with IAVI’s lead clinical candidate,
Ad35. The Sendai candidate is delivered intranasally to elicit mucosal immunity, as well
as immunity in blood.
2. Canine Distemper Virus (CDV) vector-based candidate: This was prioritised in 2012
and is in preclinical development, including non-human primate studies to guide the
administration and dosing of vaccines. Preliminary data has shown control of SIV in
monkey studies.
3. Cytomegalovirus (CMV) candidate: This had shown promise as a protective AIDS
vaccine but the planned clinical trial of the prototype CMV vaccine candidate was deprioritised in 2011 due to safety considerations. However, research by IAVI
collaborators indicates that newer safer versions are pending.
4. Vesicular Stomatitis Virus (VSV) vector-based candidate: The immune response to
VSV in initial experiments was lower than expected and therefore IAVI deprioritised
VSV as a clinical candidate.
Output Indicator 2- Number of neutralising antibodies isolated
The pace of discovery of new broadly neutralising antibodies has quickened since the first of
these were identified in 2009, with over two dozen identified. IAVI and its partners have
reported the the discovery of broadly neutralizing antibodies (bnAbs) against HIV. These are
already proving essential tools in the design of future vaccines. The isolation of bnAbs was
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initiated by a major clinical effort to identify thousands of HIV infected individuals in Africa and
around the world. These individuals were screened for those rare cases where bnAbs were
present. New technology was accessed from academic and industry partners and antibodies
isolated and published in major scientific journals. Broadly neutralizing antibodies have been
isolated that target 4 major sites of vulnerability on HIV. For each site multiple individual
examples of antibodies have been isolated providing a map of the possible ways that
antibodies can bind.
Researchers have made good progress in analysing and identifying the structure of these
broadly neutralising antibodies (bNAbs) and sites on HIV where they bind, to support the
design of potential vaccines. The newest antibodies appear to bind to previously unknown
sites on the HIV outer envelope, providing researchers with a bigger range of molecular
structures to use as models for vaccine design. Researchers also made good progress in
understanding how these antibodies form and how they might be induced through vaccination
to block HIV infection. There is now structural information for each of the regions targeted by
the broadly neutralising antibodies. This information will provide direct clues for the design of
immunogens that mimic the CD4 binding site, as well as previously unknown conserved
structures in the V1V2 loop and the base of the V3 loop.
Three approaches, to the identification and testing of vaccines that produce neutralising
antibodies, met important milestones:
1. vaccines that mimic the epitopes of neutralising antibodies have been designed,
synthesised, and tested in the laboratory and immunogenicity testing is about to
commence
2. vaccines that mimic the surface proteins of the HIV particle have been developed and
shown to generate some neutralising antibody titres in non-human primates
3. a by-product of IAVI’s replicating vector programme has generated vaccine leads that
should mimic an HIV vaccine particle, but in a safe form, have been tested and are
advancing.
In an additional approach to delivering neutralising antibodies, in 2011 IAVI placed one project
on an accelerated timeline – the development of AAV1-PG9, a vector mediated approach to
prevent HIV infection via antibodies, with a view to submitting the regulatory dossier by the
end of 2012. IAVI had completed Good Manufacturing Practice of AAV1-PG9 for toxicology
studies and finalised the contract for commencement of those studies by the end of 2011.
There have been delays in validation assays of bio-distribution studies, and the regulatory
dossier is now expected to be submitted to the UK’s regulatory body in the 2nd quarter of
2013. Once approved, IAVI plans to conduct a small safety Phase 1 trial of this candidate,
expected in late 2013.
In addition to scientific developments, the Neutralising Antibody Consortium (NAC 4.0) has
been restructured to achieve improved integration across NAC members and the DDL with
specific milestones to drive progress in immunogen design and vaccine development. IAVI
has also met with all major vaccine companies to discuss potential collaborations in
immunogen design. A strategy is currently being developed to add industry partners to a
broader Neutralising Antibody Consortium.
Output Indicator 3: Number of observational studies, pre-clinical and clinical trials
IAVI currently has 3 candidates in clinical development, all testing their lead candidate (based
on the Ad35 vector) in combination with other promising candidates. Immunological analyses
from the Phase 1 clinical trials on the Ad35/Ad26 and Ad35/adjuvanted protein candidates are
ongoing. The EpDNA IL -12/Ad 35 candidate entered the clinic in late 2011 and work is
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ongoing in collaborating sites in Rwanda, Kenya and Uganda. A novel feature of this
candidate is its use of a brief electrical pulse to deliver the DNA-based vaccine candidate
more efficiently. The trial builds on pre-clinical results that showed that an analogous
combination vaccine conferred a high degree of control of the simian form of HIV, and the
concept is considered a potential candidate for a Phase IIb trial.
As discussed above, VSV and CDV replicating vector candidates are in a discovery/
development phase, and the Sendai vector candidate is in pre-clinical development.
Immunogen design candidates (to elicit bnAbs) include eOD, iVSV, JFRL and BG505 (all in
discovery phase), and the AAV1-PG9 candidate in pre-clinical development.
Impact Weighting (%): 70%
Revised since last Annual Review? No
Risk: High
Revised since last Annual Review? No
Output 2: To engage in partnership those countries where the epidemic is, or is likely to
be most severe
Output 2: final score and performance description: A – output met expectations
Final results:
IAVI worked in partnerships with numerous NGO research organisations, academic,
biotechnology, pharmaceutical and government institutions in 25 developed and developing
countries, to develop and assess AIDS vaccine candidates. They play an important coordinating role in the field.
IAVI catalysed AIDS vaccine R&D efforts in innovative developing countries, e.g., an ongoing
transnational South Africa-India research collaboration (2009) and the IAVI-India HIV Vaccine
Programme, and secured Infectious Diseases as a focus area in India’s collaborative science
and technology efforts with France and Brazil (2012).
The Ragon Institute selected IAVI as a preferred development partner. International
Partnership for Microbicides utilised IAVI’s lab capacity in Rwanda to support HIV prevention
trials in 2010. An agreement with Aeras (2012) provides a broader framework for sharing
knowledge and resources across the clinical trials networks of each organisation. In 2012,
IAVI successfully piloted a product development “Central Services Facility” mechanism to
drive translational research for the field in partnership with the Bill and Melinda Gates
Foundation and selected Collaboration for AIDS Vaccine Discovery (CAVD) grantees. Since
2008, IAVI added substantial core capacity for translational research with the opening of its
Vaccine Design and Development Lab in New York (2008) and the HIV Vaccine Translational
Research Lab in New Delhi, a joint venture with the Indian government (2012).
Output indicator 1: Number of IAVI-sponsored sites with sufficient technical, financial,
operations and compliance capacity to conduct a vaccine trial (IAVI HIV Vaccine Trial
capacity)
IAVI has a strong history of developing both human and infrastructure clinical trial capacity in
developing countries and has supported the development of a network of clinical research
centres and laboratories in Sub-Saharan Africa. Three Phase 1 clinical trials are currently
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taking place at various IAVI-sponsored sites in East and Southern Africa. IAVI have continued
to work in partnership with a range of developing country stakeholders - governments,
researchers, technicians, communities etc. to strengthen their capacity to engage in all
aspects of the vaccine development process.
IAVI have delivered training to build research capacity, for example on Good Clinical
Laboratory Practice and scientific writing. IAVI has provided extensive training programs for
clinical and laboratory personnel to ensure that collaborating research centres operate at
international standards of Good Clinical Practice and Good Clinical Laboratory Practices;
gender training, and training in Voluntary Counselling and Testing (VCT). They have
developed, field tested, and implemented a series of new tools, training aids, and vaccine
literacy programming in communities where they work, such as a new Quality Improvement
(QI) Toolkit pilot tested at three research centres in East Africa; launched IAVI’s Vaccine
Literacy Toolkit with the Medical Research Council of South Africa at the South African AIDS
Conference; and furthered steps toward a guidance document for Community Advisory Boards
in China.
For example, in 2012, 106 staff received basic and advanced Good Clinical Practices (GCP)
training, 180 staff at 9 collaborating centres completed a newly revamped interactive refresher
course on GCP and 40 study physicians/investigators participated in safety mentoring to
improve understanding of safety assessment in clinical development of candidate vaccines.
Good Clinical Laboratory Practices training was delivered to 74 people and a Train the
Trainers programme transferred skills to local staff to increase access. IAVI also supported 10
staff from African research centres to participate in a 6 day long scientific writing training
course. IAVI further supported the Kenya AIDS Vaccine Initiative (KAVI) to become a regional
centre for studies of mucosal immunity by training researchers there to collect and prepare
mucosal tissue samples and use them to conduct highly standardised and accurate
immunological assays. Additionally, IAVI have supported clinical capacity through the
installation of improved IT equipment, the provision of increased bandwidth at 3 African
centres and the provision of liquid nitrogen production plants at 2 African centres.
To support national vaccine planning, IAVI participated fully in the process of developing
Kenya’s third national HIV vaccine plan and commenced a study in China on national vaccine
R&D policy framework.
Given the strength of India's existing vaccine industry and the government's interest in
developing the capacity to innovate in the biopharmaceutical field, IAVI established a scientific
hub in India for IAVI's broadly neutralising antibody programme and have signed an
agreement with the Indian Government to jointly establish, fund and operate an HIV Design
programme in India with the development of a laboratory that will work in collaboration with
Indian national institutions. IAVI, and the East African clinical research partners, have worked
with AVAC and UNAIDS for pilot training of Good Participatory Practices (GPP) which is
central to efforts to strengthening community-based groups for broader community
engagement and support for clinical trial preparation and enrolment
Output indicator 2: Number of IAVI-sponsored sites where social research has been
conducted to inform existing research activities or to plan future activities.
IAVI have conducted social science research projects to inform clinical trial recruitment,
retention, including a landmark study of at-risk fishing communities along the shore of Lake
Victoria; collaborated with key government agencies in the U.S., South Africa, and Brazil to
convene country-level workshops on the integration of a social sciences research agenda into
AIDS vaccine clinical research.
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In addition, IAVI have monitored changes in risk to identify and understand most-at-risk
populations, including men who have sex with men (MSM), sex workers and individuals with
multiple partners in Kenya, South Africa and Uganda. IAVI and partners have developed and
published evidence–based on-line training tools for healthcare workers working with MSM,
and a guidance document on conducting HIV research on MSM in rights constrained
environments.
IAVI stopped research looking at the behaviour of discordant couples in Uganda, Rwanda and
Zambia on the basis of data demonstrating treatment as an effective prevention strategy –they
considered that the discordant couples risk group was no longer suitable for HIV vaccine
efficacy trials.
Impact Weighting (%): 15%
Revised since last Annual Review? N
Risk: High
Revised since last Annual Review? N
Output 3: To promote public policies that support vaccine Research & Development and
future access
Output 3: final score and performance description: A – output met expectations
Final results:
Recognising the challenges of the current economic climate; and a general trend towards HIV
funding becoming part of a broader health agenda, IAVI has been strengthening its outreach
and influencing efforts, focused around key themes. The newly appointed Director of
Advocacy and Policy aims to expand and strengthen partnerships with governments,
policymakers, NGOs, civil society and the media to ensure that AIDS vaccines and
investments in AIDS vaccine research and development remain high on global health,
development and research agendas.
Output indicator 1: Number of policy options proposed by IAVI to support HIV/AIDS
vaccine development.
IAVI has engaged and informed constituencies, and promoted policies and partnerships, to
help maintain political and financial support for AIDS vaccine research. For example, IAVI
secured express support for AIDS vaccine research in the parliaments of the EU, Germany,
Denmark, Spain and Portugal; with civil society groups and African Heads of State at the
International AIDS conference in Vienna; and worked with UNAIDS to organise a briefing for
UN delegates at the MDG Summit on the importance of investing in AIDS vaccine research to
achieve health-related MDGs. IAVI worked with partners to secure language in the 2011 UN
Political Declaration on HIV/AIDS supporting the importance of HIV prevention tools including
vaccines and the development of female microbicides. At country level, IAVI co-sponsored an
International Symposium with the Department of Biotechnology in India, which featured
presentations of research advances for diverse vaccines such as E coli O157, TB, malaria,
HIV, and rotavirus. Half of the meeting was dedicated to public policy discussions of how to
achieve greater access and coverage of Indian children to licensed vaccines, since the
national rate lags significantly behind poorer neighbours such as Pakistan, Bangladesh and
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Nepal.
IAVI entered into renewed partnerships with a range of relevant organisations with a common
interest in promoting HIV/AIDS vaccine development, including with AVAC; WHO’s African
AIDS Vaccine Programme (AAVP); and the Global Youth Coalition on HIV/AIDS. They also
developed new relationships, for example, with the International HIV/AIDS Alliance Regional
Technical Support Hub in East Africa.
Indicator 2: Developing long term sustainable funding case for HIV and AIDS vaccine
development
The funding environment for HIV/AIDS vaccine research and development has been
challenging throughout this funding period. The global economic crisis is now stabilising, but
there remains limited growth in funding for HIV and global health R&D. Overall funding for
2011 (latest data available) was 12% down from its peak year in 2007..
IAVI is operating in a similarly challenging political landscape, in which the development arena
is re-orientating towards stronger links with trade, security, economic development. Further,
whilst the MDG process placed development aid high on political agendas, there is a concern
that the post-MDG agenda will broaden the number of development issues without additional
funding, which will add additional pressure to reduce vaccine R&D budget commitments.
In August 2012, and following consultation with donors and other stakeholders, IAVI
announced a range of organisational and programme changes that were designed: to achieve
balance between anticipated income and expenditure; and to ensure the long term
sustainability of the organisation whilst delivering on its core remit of developing a safe,
effective and accessible HIV vaccine. IAVI’s budget was set at $60million in 2013, a reduction
of approximately 20% on 2012. Staffing was correspondingly cut, with a reduction of 49 posts.
IAVI reorganised its work into 5 (from 9) functional areas and changed their leadership
structure accordingly – four senior management posts were lost, and the responsibilities of
those posts shifted to other Senior Management Team members. IAVI have prioritised their
budget to concentrate on programmes that had potential to make the greatest impact on HIV
vaccine development, they also shifted the focus of their research downstream to accelerate
the advancement of an HIV vaccine candidate. IAVI retained its value on collaboration with
partners to advance HIV vaccine research as effectively as possible, and is committed to
working with developing country partners and researchers in pursuit of this aim.
IAVI continues to focus on improving business practices and organisational efficiencies,
including a process of changing the culture within the organisation itself. They plan to use
feedback from a recent partner survey to gauge the status of their partnering reputation and to
design interventions in 2013 to improve on this. IAVI have undertaken a Business Process
Initiative, focusing on 6 high impact, cross-departmental business processes with a goal of
simplifying, saving costs, or reducing the required staff effort. 4 of these processes have now
been implemented and the remaining 2 will be implemented in 2013. IAVI’s goal to manage its
overall budget to within 5% of target was reached in 2012.
Impact Weighting (%): 15%
Revised since last Annual Review? NO
Risk: High
Revised since last Annual Review? NO
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Section B: Results and Value for Money.
1. Achievement and Results
1.1 Has the logframe been changed since the last review? No
1.2 Final Output score and description: A – outputs met expectations
1.3 Direct feedback from beneficiaries
IAVI has partnered with developing countries, those hardest hit by the HIV pandemic in pursuit
of their goals, and engaged with political leaders, developing country researchers, civil society
organisations, communities etc.
IAVI have co-hosted an International Vaccine Symposium with the Government of India,
provided input to South African Strategic Plan for HIV/AIDS and the development of the
National AIDS Vaccine Plan for South Africa. They have helped develop HIV research
capacity in East and Southern Africa and continue to work in partnership with clinical research
centres in Africa to undertake research. They have continued to work in partnership with
Uganda Virus Research Institute and support partnerships with different stakeholders in
Uganda, including Most at Risk populations (fishing communities, sex workers etc.),
Community Advisory Boards, Parliamentarians and the media.
IAVI’s new strategic plan emphasises the continued importance of partnership working and
collaboration with others.
In 2012, IAVI surveyed 103 partners, including R&D and advocacy partners and donors. There
was a 51% response rate and overall, 42% of respondents rated IAVI as an “excellent”
partner. A number of areas of strength were identified, including interaction, technical
competency and giving appropriate credit to partners.
Areas identified for improvement were the clarity of IAVI’s process and rationale for decision
making, communication of strategies and priorities, treating partners as equals and
improvement in IAVI’s capacity to partner in the previous 12 months.
In response to these findings, IAVI have integrated “partner of choice” indicators in the 2012
performance process and disseminated revised Organisational Values to all staff. It has
retained a consultant to advise on further improvements in decision-making and prioritisation
transparency, and has included specific metrics to improve in the 2013 organisational
objectives.
1.4 Overall Outcome score and description: A – Outcomes met expectations
1.5 Impact and Sustainability
Summary of progress
Over the grant period, IAVI has advanced HIV vaccine research. It has developed 16 vaccine
candidates and advanced 7 to clinical trials. There have been major steps forward in
immunogen research to stimulate bnAbs, with over 60 immunogens screened per year and the
isolation of a number of novel broadly neutralising antibodies which allowed for research into
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their structure. IAVI is currently using this new information to design experimental vaccines to
re-elicit similar antibodies in people opening a path to a new, more potent, and broadly active
vaccine.
IAVI has engaged in partnership working in countries with a significant burden of HIV/AIDS
including South Africa, India, and Rwanda. Trials are taking place in East and Southern Africa
and IAVI has delivered training to build research capacity in these areas. It also worked with
governments to support their vaccine R&D policies, including in Kenya and China.
To facilitate IAVI’s sustainability, it has secured support for AIDS vaccine research from
Governments of the EU including The Netherlands, Denmark, Ireland, Spain and Norway and
renewed partnerships with a range of organisations with a common interest in HIV/AIDS
vaccine development.
During the grant period, IAVI underwent a significant restructuring in its organisational design,
in part in response to consultation with donors and other stakeholders, and in part as funding
levels have decreased. This restructuring has involved cutting staffing levels, reducing the
number of senior management posts, prioritising only programmes that had the greatest
potential and shifting their research focus further downstream.
Sustainability
IAVI has advanced research in the HIV vaccine field by broadening the vaccine pipeline and
accelerating the development of promising vaccine candidates. The research findings (both
positive and negative) have provided insight into HIV vaccine development, upon which future
research can build. Therefore, the benefits arising from this investment will be sustained
beyond the end of the project.
In the mid-term of the project grant, there were concerns about the sustainability and
management of IAVI, centering on its reduced budget and top-heavy management structure.
Following consultation with its stakeholders, including donors, IAVI responded to these
concerns with both changes to its management structure and more effective management of
its reduced budget. These significant changes have allayed donor concerns and in doing so
have increased the sustainability of the initiative in the longer term.
Progress towards achieving impact
IAVI’s primary aim, to develop an effective AIDS vaccine that both protects against new
infection and controls existing infection, is high-risk and ambitious. At the conclusion of this
grant period, the AIDS vaccine research field remains some way from achieving this aim.
There have been just four clinical efficacy trials completed to date: only one showed a modest
effect at preventing new infections (RV-144) and two have shown an increase in HIV infections
in the vaccine arms of trials (albeit not reaching statistical significance in one trial).
Despite this modest progress downstream in the AID vaccine research pipeline, there are a
number of promising candidates within the IAVI portfolio that are building on successes to date
(e.g. Ad35 trials). Further, IAVI’s portfolio has a number of research approaches to increase
the chances of identifying a successful vaccine strategy. Combined with a more efficient
management structure and better prioritisation of vaccine candidates, there are reasons to be
optimistic about the future of AIDS vaccine research and IAVI’s place within it. The difficulties
to date reflect the high-risk nature of vaccine research, but IAVI’s progress over the grant
period suggests that it is making a substantial contribution to achieving its primary aim.
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2. Costs and timescale
2.1 Was the project completed within budget / expected costs: Yes
2.2 Key cost drivers
Vaccine development is a high risk, long term and costly process, particularly during the
clinical trials phase. The PDP model explicitly aims to manage resources to ensure that there
are funds available to test the most promising products as they are developed. This includes
widening partnership with the private sector in low, middle and high income countries and
leveraging of resources, in-kind contributions and expertise; working with other not-for-profit
organisations to share costs wherever possible. But it is worth noting that vaccine
development is more resource intensive than research and development activities in other
areas such as diagnostics and drug development.
2.3 Was the project completed within the expected timescale: Yes
3. Evidence and Evaluation
3.1 Assess any changes in evidence and what this meant for the project.
There is still an urgent need for a new vaccine against HIV. Recent progress is mixed (see
table below), with encouraging findings from the RV144 trial as the introduction of even a
partially effective vaccine to the portfolio could help to achieve the step-change needed over
the next 20 years to help end the AIDS epidemic, especially in high prevalence settings – and
in the process lessen treatment costs. However, the findings from the NIAID-VRC sponsored
trial (HVTN 505) and Merck rAD5 trial were considerably more disappointing, in spite of
providing further research questions to investigate the cause of the vaccine failure.
Table 1: Vaccine efficacy trials. Adapted from Koff WC. HIV vaccine development: challenges
and opportunities towards solving the HIV vaccine-neutralising antibody problem. Vaccine.
2012: 30; 4310-4315.
Year
Candidate
Prevention of HIV infection
Control of
HIV
infection
2003
VaxGen: gp120
No
No
2007
Merck rAd5: Gag, Pol, Nef
No – more infections in
vaccines than placebo
No
2009
RV-144 (Sanofi/VaxGen)
Canarypox Gag, Pol, Env/gp120
boost
31% efficacy
No
2013
NIAID-VRC: DNA + Ad5; gag-pol-
No
No
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nef: Env A, B, C (HVTN 505)
3.2 Set out what plans are in place for an evaluation.
A robust World Bank Evaluation of IAVI in 2009 made a number of priority recommendations
covering a range of issues (strengthen the link between the scientific advisory committee and
the IAVI Board; improve communications about governance and key decisions; continue
collaboration with others and explore a more formalised arrangement for sharing clinical
practice; continue to refocus its policy activities; and further strengthen coherence of its
approach to strategic planning and monitoring and evaluation). IAVI responded positively to all
of these and took them into account when developing their new Strategic Plan.
In 2011 IAVI commissioned an independent review of its policy and advocacy programmes to
guide future strategic direction, the outcomes of this exercise are also reflected in the Strategic
Plan. IAVI consulted donors, via a roundtable meeting, on a draft version of the Strategic Plan
and took account of their views before finalising and publishing the document –DFID were
active in this process.
4. Risk
4.1 Risk Rating (overall project risk): High
Did the Risk Rating change over the life of the project? No
4.2 Risk funds not used for purposes intended
This is a low risk.
IAVI’s Finance & Administration department, under the leadership of the Chief Financial
Officer (CFO) provides a comprehensive system of internal controls, financial management
and compliance to ensure accountability and sound stewardship of donor resources.
An independent Financial audit of IAVI’s financial position is undertaken annually. Copies of
unqualified Audited Financial Statements for 2011 have been examined by DFID.
The provision of core funds to manage its portfolio of potential vaccines is a way to manage
the risk that any one project is unsuccessful and that work will stop. The organisation is able to
reassign funds to more promising projects and ensure that work continues.
There were full and open discussions about finances, financial management and quality
assurance, and risk management at the donor meetings in 2012and 2013. The organisation
was very open to all comments from all donors about its internal processes and procedures.
4.3
Climate and Environment Impact
There are no significant environmental impacts of IAVI’s work at this time. As with other PDPs,
in the longer term the environmental impacts of IAVI’s activities should be positive with
improved treatments / prevention of disease in poor populations contributing to more effective
and efficient use of drugs and associated health services.
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5. Value for Money
5.1 Performance on VfM measures
Funding vaccine development through a PDP such as IAVI provides value for money through:
•
The use of a portfolio approach which allows funding to be redistributed if individual
projects are stopped if they do not meet their milestones;
•
The leveraging of contributions (resources, funding, access to drugs and other in-kind
resources) from the private sector (in low, middle and high income countries);
•
Support for the continued development of the most promising candidates: facilitating
opportunities to explore innovative partnerships with private and public sector
organisations (in many different countries including low and middle income) to reduce
costs
IAVI further enhances its value for money through strong partnership working with policymakers, influencers, other researchers, civil society and communities –such involvement
significantly increases the likelihood and timeliness of vaccine uptake in endemic countries.
IAVI have received additional funding from the Gates foundation so that its expertise in
translational research can be used by other groups – thus providing a resource for other
researchers working towards its own goals.
5.2 Commercial Improvement and Value for Money
Significantly reduced funding levels have threatened the sustainability of the organisation in
recent years, and IAVI have responded very well to managing this over the last year – they
have improved business practices and organisational efficiency and made the organisation
leaner; and they are looking to develop more collaborative partnerships to further mitigate
risks and improve efficiency across the HIV vaccine community. In the longer term, the
approach outlined in their new Strategic Plan should continue to mitigate financial risks whilst
making IAVI, and HIV vaccine research, more efficient.
5.3 Role of project partners
DFID is one of a number of donors all of whom are involved through regular discussions with
the programme directly and through various international and WHO based fora. All donors are
aware of the financial constraints and the need to identify ways to increase value for money.
Ensuring value for money in developing products for use in low income countries, where there
is no viable commercial market, is central to the way PDPs work with their partners from a
range of different backgrounds, including private sector organisations, academic researchers,
advocacy organisations and local community groups.
Again might be worth saying something about the stakeholder consultation and how IAVI have
used that to strengthen the role of their partners
5.4 Did the project represent Value for Money : Yes
Over the grant period, IAVI has made a significant contribution to HIV vaccine research with
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broad portfolio of vaccine candidates in Discovery, Preclinical and Clinical trials stages. IAVI
received criticism from donors in the mid-term of the grant period relating to its top-heavy
management structure and limited collaboration with potential partners. In response to this,
and through consultation, IAVI has undergone significant rationalisation and restructuring,
together with improved prioritisation of vaccine candidates and better partnership working,
which has improved its efficiency as an organisation. Consequently, IAVI has been judged to
have delivered value for money, which was particularly evident in the latter half of the grant
period.
6. Conditionality
6.1 Update on specific conditions
Not applicable
7. Conclusions
Over the grant period, IAVI has made a substantial impact on HIV vaccine research and
development. It has developed 16 vaccine candidates, prioritised 10 for further development
and advanced 7 to clinical trials, primarily in Africa. Both of the R&D approaches (Cellmediated immunity and Broadly neutralising antibodies) have delivered a number of promising
candidates. The changes to make the organisation leaner and more efficient are welcome,
and implementation of the new Strategic Plan should reap further efficiencies and improved
value for money in the longer term.
8. Review Process
The review was carried out by members of the Human Development Team in DFID’s
Research and Evidence Division following active participation in 2012 and 2013 at the donor
roundtable consultation meetings and follow up discussions with IAVI’s Chief Executive Officer
and other staff members. During the donor meetings the range of challenges facing IAVI (both
technical and business related) were fully and openly discussed.
Account was also taken of further supporting materials including reports from the IAVI website,
annual reports and regular e-mail updates.
As a PDP competition for PDP funding (for the period 2013 -18) was launched in February
2012, there has been minimal very recent contact with IAVI to minimise the risk of conflict of
interest. Any discussions with the programme have been limited to reviewing progress against
the existing performance framework, risk, financial and programme management.
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