New Hope for an HIV Vaccine
Forty Years since the HIV global epidemic began,
new hope has arisen
in the hunt for the so-far-elusive vaccine. The US pharmaceutical and biotech company Moderna, which rolled out the world's first Covid-19 vaccine, recently announced human trials for
two HIV vaccines. These are based on the same platform—mRNA—as Moderna’s Covid vaccine.
The human trials Moderna will be trailing two versions of its
vaccine candidate. This is the first mRNA vaccine against HIV to be trialled in humans.
According to the US National Institutes of Health's(NIH) clinical trials registry,
56 HIV-negative people between the ages of 18-50 have been recruited in the
phase-1 trial.
There will be four groups in the first phase,
with two receiving a mix of the mRNA vaccine versions and two receiving one or
the other. The trial is not blind: Participants will know which group they are
in. The two mRNA vaccines will eventually be used alongside another vaccine, developed
by the International AIDS Vaccine Initiative (IAVI).
The hypothesis is that the two Moderna
vaccines have the potential to prime a specific type of B-Cell to produce effective
neutralizing antibodies, and the other vaccine will stimulate them to do so.
The study sponsored by IAVI and others is expected to run until May 2023, with the
first phase lasting around 10 months.
HIV Burden
HIV has claimed 36.3 million lives so far,
according to the World Health Organization (WHO). There were an estimated 37.7 million
living with HIV at the end of 2020.
There is still no cure. However, with increasing
access to effective prevention, diagnosis and care, including for opportunistic
infections, HIV infection has become a manageable chronic health condition in
recent years.
According to the National AIDS Control Organization's
India HIV Estimation 2019 report, there were an estimated 23.48 lakh people
living with HIV in 2019. Overall, the estimated adult (15-49) HIV prevalence trend
has been declining in India since the peak in 2000, and has been stabilizing in
recent years.
The Elusive Vaccine
HIV tends to change its envelope so rapidly
that it is difficult to provide any antibody cover. Additionally, the envelope proteins
are covered by a sugar coating that affects generation of an immune response, said
Dr. Cangakhedkar, former director of National AIDS Research Institute, and former
Head, Division of the Epidemiology and Communicable Diseases division of Indian
Council of Medical Research (ICMR).An anti-HIV vaccine has been a challenge
given the fact that it is a fast replicating virus and tends to mutate rapidly…
Escape mutants are generated rapidly due to the high replication rate of HIV.
Even when antibodies are made, by the time
they are produced, the virus rapidly evolves and the antibodies do not
neutralize the virus. This rapid mutation allows the virus to escape the
antibody response, said leading vaccine scientist. For example, the virus
sequences of an untreated individual with HIV tested three months apart would
show differences between the later and earlier viruses.
Previous Attempts
Previously inactivated forms of the virus and
adenovirus vector- based vaccines have been tried, but have not worked. A
handful of HIV clinical trials were very carefully set up and conducted, but were
stopped it when vaccines did not work, or in the case of adenovirus vectored
vaccine where there was a signal that participants were more susceptible to
HIV, instead of being protected.
The most important challenges in HIV vaccine
development has been the inability to identify the exact correlates of immune
response that need to be stimulated to protect against HIV and the enormous diversity
potential of the virus. Inducing broadly neutralizing antibodies against HIV
envelope protein and CD8 T cell responses has been the major focus.
mRNA: way
forward
The Moderna trial is different as it allows
one to use technology to design and develop a vaccine really fast. It is similar
to the Covid-19 vaccine development work so that the body's cells can produce
the virus's spike envelope to trigger an immune response.
In the HIV context, the mRNA platform has shown
promising results in vitro and monkey studies, and it would be useful to test it
in human clinical trials, Dr Pujari said. The hope is that this platform has the
ability to tweak the RNA to address emerging variants and their potential to
escape immune response. “Until now the major challenge for the development of mRNA
vaccines was lack of efficient delivery technologies. This has been overcome
successfully with Covid-19 mRNA vaccines.
Preventive
& Therapeutic
Experts say two approaches can be considered
for an HIV vaccine a preventive and therapeutic one. A preventive approach would
have to check how many vaccinated people develop HIV post-vaccination, or whether
the vaccinated ones can resist infection. A therapeutic approach would result in
an immune response that would attack the infected cells and prevent further replication.
Therapeutic vaccines have been tried without
success to achieve a functional cure. It would be interesting to study the
performance of the mRNA platform in this context. For a therapeutic vaccine to work,
it has to stimulate cells to generate broadly neutralizing antibodies, Dr
Cangakhedkar said. “While antiretroviral therapy controls the infection, one has
to take drugs lifelong and there are side effects. A curative modality with a therapeutic
vaccine and medicine can cure HIV.
However, this has to be tested over a period of
time, to assess whether the immune response is sustained. With HIV incidence
having gone down, it reduces the risk of exposure to HIV. Moreover, use of other
preventive measures adds to reduction in HIV incidence. These factors pose
challenges in undertaking these trials and finding out whether or not the vaccine
producing broadly neutralizing antibodies actually prevents HIV infection.