W26052102 Imbokodo & Mosaico updates, plans for correlates and sieve analyses.
Summary
TLDRThe script discusses an extensive public-private partnership working on a global prophylactic HIV vaccine. The goal is to develop a vaccine effective against diverse HIV strains, using mosaic antigen designs. Two ongoing efficacy studies, Imbokoto and Mosaico, are evaluating the vaccine in different populations and transmission modes. The studies involve immunogenicity evaluations, sieve analysis, and immune bridging to support a broad evidence package. The aim is to identify immune markers associated with vaccine efficacy and understand how and where the vaccine could be used globally.
Takeaways
- 🌐 The program aims to develop a global prophylactic vaccine for HIV, targeting diverse strains worldwide, not just strain or plate-specific vaccines.
- 🔬 Mosaic antigen designs by Betty Gorber are central to the vaccine development, using a heterologous regimen for delivery.
- 📚 Two ongoing efficacy studies, Imbokoto and Mosaico, are complementary and focus on different HIV clades and transmission modes.
- 📊 Imbokoto is conducted in Southern Africa with a focus on clade C viruses, while Mosaico evaluates in the Americas and Europe, focusing on clade B.
- 👥 The studies involve different demographics: Imbokoto targets young women (18-35), whereas Mosaico includes MSM and transgender individuals (18-60).
- 💉 The vaccine regimen involves multiple vaccinations with different components to enhance immune responses against various HIV strains.
- 🧬 Sieve analysis is being conducted to understand the vaccine's effect on viral gene sequences and to identify mechanisms of an imperfect vaccine regimen.
- 🔄 Immunobridging studies are necessary to connect the efficacy of the vaccine regimens across different studies and populations.
- 📈 A pilot immunogenicity study is underway in the Imbokoto study to characterize vaccine responses in the study population and identify potential predictors of immune responses.
- 🧬 Future immune and correlates analyses in the Mosaico study will build upon the findings and learnings from the Imbokoto study.
- 🌟 The ultimate goal is to identify strong immunologic markers associated with vaccine efficacy, which could help define the use of such vaccines globally.
Q & A
What is the primary goal of the HIV vaccine program mentioned in the transcript?
-The primary goal of the program is to develop a global prophylactic vaccine that is not strain or plate-specific but is relevant for the globally diverse strains of HIV, based on mosaic antigen designs.
Who developed the mosaic antigen designs used in the vaccine?
-Betty Gorber developed the mosaic antigen designs used in the vaccine.
What is the significance of a heterologous vaccine regimen in the context of this program?
-A heterologous vaccine regimen is used to deliver the mosaic antigens and for Gag, Pol, and Env, which are coated by Ad26, as well as soluble trimeric gp-140, to enhance the vaccine's efficacy.
What are the two ongoing efficacy studies mentioned in the transcript?
-The two ongoing efficacy studies are the Imbokoto study, which uses the vaccine HBTN705, and the Mosaico study, which uses the vaccine HBTN706.
In which regions are the Imbokoto and Mosaico studies taking place?
-The Imbokoto study is taking place in five countries in Southern Africa, while the Mosaico study is conducted throughout the Americas and Europe.
What is the predominant virus clade circulating in the Impacto study?
-Clade C is the predominant virus circulating in the Impacto study.
What are the differences in the study designs between Imbokoto and Mosaico?
-Both studies have a similar design with a one-to-one randomization and participants receiving two vaccinations. The difference is that in Mosaico, the third and fourth vaccinations also include the mosaic gp-140 component to expand immune responses.
What is the purpose of the immunobridging studies mentioned in the transcript?
-The immunobridging studies aim to support a broad evidence package for the use of the vaccines by bridging between different vaccine regimens, populations, and plates to show the vaccine's efficacy across various conditions.
What are the objectives of the pilot immunogenicity study currently taking place in the Imbokoto study?
-The pilot immunogenicity study aims to characterize the immunogenicity of the vaccine regimen in the study population, understand the temporal relationships between immune responses, and develop predictors of immune responses to inform future analyses.
What is the sieve analysis, and how does it contribute to the vaccine program?
-The sieve analysis involves sequencing all viral genes encoded in the vaccine to characterize differences between virus sequences in the study arms. It helps elucidate the mechanisms of an imperfect vaccine regimen and guides future iterations and hypotheses for immune correlance analyses.
How do the results from the Imbokoto study plan to inform the Mosaico study?
-The results from the Imbokoto study will allow for the definition and testing of specific correlates hypotheses in the Mosaico study, helping to identify immune markers associated with risk of infection and defining the use of the vaccine.
What is the hypothesis regarding the extrapolation of vaccine efficacy to other HIV clades?
-The hypothesis is that if efficacy can be demonstrated and similar levels of immune responses are seen across clades, then the vaccine could also prevent infection by other diverse strains of HIV, which needs to be supported by strong immunologic markers associated with vaccine efficacy.
Outlines
🌐 Global HIV Vaccine Development
The script discusses the development of a global prophylactic HIV vaccine, emphasizing a public-private partnership effort spanning 12 years. The goal is to create a vaccine effective against diverse HIV strains worldwide, not just specific ones. The vaccine strategy involves mosaic antigen designs by Betty Gorber and a heterologous regimen with different components like Ad26 and soluble trimeric gp-140. The script also outlines two ongoing efficacy studies, Imbakoro and Mosaico, which aim to cover a wide range of HIV clades and transmission modes. The studies are designed to evaluate the vaccine's efficacy in different populations and regions, with a focus on intravaginal and interrectal transmission. The summary also mentions the importance of immunobridging studies to support a broad evidence package for vaccine use.
🧬 Immunogenicity Evaluations and Correlates of Protection
This paragraph delves into the ongoing pilot study within the Imbokoto trial, focusing on characterizing the immunogenicity of the vaccine regimen in the study population. The aim is to understand the temporal relationship between immune responses and factors influencing them at baseline and post-vaccination. The study seeks to develop predictors of immune responses and select unique markers for case-control endpoints in correlates of protection analysis. It also includes a detailed look at various types of immune responses, such as binding antibodies, IgG3, IgA, phagocytosis, cytotoxicity, and T-cell functionality. Additionally, the script describes the sieve analysis to characterize viral gene differences between study arms and the mechanisms of an imperfect vaccine regimen. The paragraph concludes with plans for immune and correlates analyses in the Mosaico study, building on lessons from previous studies like RP144, 505 studies, and NHP challenge studies.
🤝 Acknowledging Partners in HIV Vaccine Research
The final paragraph is a brief acknowledgment of the various partners involved in the HIV vaccine research program. It expresses gratitude to longstanding partners, the development team at Johnson & Johnson, clinical teams, leadership, and the sites and teams from both the Imbokoto and Mosaico studies. The speaker thanks the audience for their attention, highlighting the collaborative nature of the research efforts.
Mindmap
Keywords
💡HIV Vaccine
💡Mosaic Antigen
💡Heterologous Vaccine Regimen
💡Clades
💡Modes of Transmission
💡Efficacy Studies
💡Immunogenicity
💡Correlates of Protection
💡Vector Immunity
💡Sieve Analysis
💡Extrapolation
Highlights
The program aims to develop a global prophylactic vaccine for HIV, not strain or plate-specific, but relevant for diverse strains worldwide.
The vaccine is based on mosaic antigen designs by Betty Korber, delivered through a heterologous regimen.
The vaccine development involves a public-private partnership effort spanning over 12 years.
Two ongoing efficacy studies, Imbokoto and Mosaico, are evaluating the vaccine in different regions and populations.
Imbokoto focuses on HIV clade C in southern Africa, while Mosaico evaluates clade B in the Americas and Europe.
Different modes of transmission are considered in the studies: intravaginal for Imbokoto and interrectal for Mosaico.
The study design includes a 1:1 randomization with participants receiving multiple vaccinations and follow-ups.
Mosaico includes the mosaic gp-140 component to expand immune responses against diverse clades.
Immunobridging studies are conducted to show the vaccine's efficacy across different regimens and populations.
A pilot study in the Imbokoto trial is characterizing the immunogenicity of the vaccine regimen in the study population.
Temporal relationships between immune responses and factors influencing them are being analyzed.
Development of predictors of immune responses, such as neutralizing antibodies, age, or body mass index, is underway.
The pilot study aims to identify unique markers for inclusion in the first tier of case control endpoints.
Sieve analysis is initiated to characterize differences between viral sequences in the study arms.
Learnings from previous clinical studies, such as RP144 and NHP challenge studies, guide the current approach.
The goal is to identify immune markers associated with risk of infection to define the vaccine's utility.
If efficacy is demonstrated, the hypothesis is to extrapolate protection to other HIV clades and transmission modes.
Strong immunologic markers are needed to support the extrapolation of vaccine efficacy to diverse HIV strains.
Transcripts
[Music]
hpx2008 and hp 10705
we also have uh other names in bokodo
um hbtn706 also mosaico
that's sometimes easier for people to
worry about and we'll
uh show you the current i um thinking on
our plans for correlates and civ
analyses in this program
so all of this work is a part of a very
uh extensive public private
partnership effort with with many people
who've been involved in this program
um over its uh last 12 years
and our goal is is not to work on a
strain specific or plate-specific
vaccine but a global prophylactic
vaccine that'll
be relevant for the globally diverse
strains of hiv
and that's based on mosaic antigen
designs developed by betty gorber
and those are delivered through the use
of a heterologous vaccine regimen
with the mosaic antigens and for gag
paul and on been coated by add26
as well as soluble trimeric gp-140
envelope peruvians
so in consideration of evaluating
efficacy we're obviously worried about
clade diversity
but also making sure that vaccines are
relevant against multiple modes of
transmission
and also valuable in the
context where prep is widely used
um so currently for this program there's
two complementary efficacy studies
ongoing
um seven of hbtn705 is in vocoder
706 is mosaico um imbakoro's in
five countries in southern africa
whereas mosaic goes
throughout the americas and europe uh
clade c is the predominant uh viruses
circulating
in the impacto study whereas in mosaic b
will evaluate heterosexual young women
um
age 18 to 35 well compared to
msm and transgender individuals 18 up to
60 years old
and the modes of transmission between
these two are also different it'll be
primarily intravaginal transmission
uh versus interrectal transmission so
combined between these two studies
though
there is a good coverage
for both the uh major clades that are
circulating globally
as well as the major uh populations
and uh routes of transmission that need
to be addressed
uh mosaico this is a quick overview of
the study design
it's a one-to-one randomization
participants get two vaccinations
either with the um tetravalent
at 26 mosaic followed by two more
vaccinations in one
six and 12 with the add 26 mosaics
combined
and clad cgp140 they're followed up to
month 24
and then in a stage 2 analysis until
month 36.
mosaico has very much the same design um
the only difference is that in the third
and fourth vaccinations
uh there's also the inclusion of the
mosaic gp-140 component
this was shown to expand the clade b
and non-clade c immune responses
without while not interfering with the
clad c responses so we think this will
be a better
um antigen combination for a for a
globally useful vaccine
so there's also different types of um
immunobridging so these two studies will
evaluate if the vaccines are efficacious
in specific populations
um but in order to support a broad
evidence package for the use of these
vaccines
uh we need to conduct studies that will
bridge between these two regiments
to show that what happens with the
regiment in mosaico
is also relevant for the regiment used
in the
invocative study we need to bridge
between populations to show that
uh protection that would be relevant uh
occur in
young women in southern africa is also
relevant for young women in other parts
of the world
also to bridge between plates to show
that if we can protect
uh with these regimens from uh clay b
and mosaico
that other msm and transgender
individual populations could also be
protected
in other parts of the world we're not
going to be able to bridge formally
between modes of transmission
but given that the the modes of
transmission that are being studied are
those that are
uh generally the higher risk of
infection for exposure we think that it
would
be reasonable to to argue that
meeting a high bar for transmission risk
would also protect against other
other modes of transmission
so in currently in terms of what's going
on in the invocoto study immunogenicity
valuations there's a pilot
study to characterize the um well
there's four
four objectives of it um this is
occurring right now
while the um while the follow-up stage
of the
[Music]
study is still ongoing we're going to
characterize the immunogenicity back
of the vaccine regimen in the study
population
so we've compared the we've
characterized the immunogenicity of this
vaccine regimen in general
but we need to understand how it
actually behaves
in this population uh we want to
understand the
the temporal relationships between the
immune responses
um factors that could influence immune
responses at baseline
then post third post fourth vaccination
and then one year after the vaccination
to see how
those responses relate to one another
that'll be informative for any
um time-dependent correlates of
protection analyses that could be
conducted later on
we also need to develop best possible
predictors of immune responses
such as you might consider at 26
neutralizing antibody as a
as an example of a potential baseline
predictor or
age or body mass index or things like
this
and also based on these pilot study
results we'll be able to down select the
unique markers
that'll be included in the in the first
tier of
case control endpoints for the
correlates of protection analysis
so these are the currently planned um
pilot immunogenicity evaluations
looking at binding antibodies to the
vaccine-matched envelopes
bama and the uh bama antigens against uh
sets of uh clad c envelopes um looking
at igg3
iga and igg responses phagocytosis
responses
um cytotoxicity responses um in the
infected cell assays
uh the cd4 and cd8 functionality
as well as t-cell breath evaluations by
elie spot
and um ellie spot will also look at
the responses to the pte peptides that
were used um to help design the the
mosaic antigens
and we'll also evaluate the pre-existing
vector immunity
um in parallel we're also initiating the
sieve analysis
for infections that occur throughout the
first stage of the study
so we'll sequence all the viral genes
that are encoded in the vaccine so gag
paul and on
this will help characterize differences
between the
virus sequences that occur in the two
study arms so we can see if there's
differences in the number of
founding viruses distance to the
vaccines
if there's specific sieve effects on
that are
elicited by the vaccine and this will
help elucidate
the mechanisms of an imperfect vaccine
regimen and
that will also then uh guide future
iterations
and more specific hypotheses that can be
tested in immune correlance analyses
so and then thinking uh further along
the mosaic
study is still enrolling but eventually
that
study will need to uh also conduct
immune and correlates analyses and we
want to do that
having learned as much as we can from in
bukota at the time
so everything that we've learned from
invocodo or that we're planning on for
invocoto is based on what we've learned
through the previous clinical studies
uh most through rp144 the
um 505 studies the step studies
um as well as the nhp challenge studies
so all of the learnings that we've
uh taken from these will hopefully
give us the best possible chance to
identify the immune markers that can be
associated with risk as an infection
and help define exactly when
and where and how a vaccine like this
could be used
so also when we do have uh results from
invocoto
this will then allow a specific set of
correlates hypotheses to be defined and
tested in mosaica
um so beyond the two efficacy studies
who will also want to explore if it's
possible to extrapolate
from the clades against hiv is evaluated
to other clades of hiv
where our hypothesis is if efficacy is
can be demonstrated and we see similar
levels of immune responses across glades
then we'd like to infer that vaccine
could also prevent infection
of those diverse trades in hiv and that
needs to be supported by
the identification of strong immunologic
markers that are associated with
uh vaccine efficacy so um
if imbakoto would demonstrate efficacy
in young women
then we'd have to be able to establish
hopefully
that other clades could also be
protected
from vatican transmission and
correspondingly mosaico
would also establish that efficacy for
clay b
and other clade protection could also be
inferred for intrarective transmission
so i just stopped by thanking all our
partners
many of our long-standing partners our
johnson ganton development team
uh clinical team and our leadership
the imbokoto uh all of the invocodo
sites
mosaico teams and
thank you for for your attention
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