Explained: Why Moderna’s experimental HIV vaccine may be significant

Forty years since HIV was discovered, the development of a vaccine against the virus has remained a challenge. Now, the biotech firm Moderna has started trials on an mRNA vaccine, which uses a novel approach to elicit broadly neutralising HIV-1 antibodies (bNAbs) and eventually target multiple HIV strains. First doses of the experimental HIV vaccine antigens were administered at George Washington University School of Medicine and Health Sciences in Washington DC this week.

The technology

The vaccine uses the same technology as Moderna’s Covid 19 vaccine. It uses mRNA, or messenger RNA, which teaches the body’s cells how to make proteins that trigger immune response.

BNAbs are produced by certain types of B cells, which are rare: one in 300,000 B cells have this capability. The vaccine aims to stimulate production of bnAbs that can act against many variants of HIV.

The immunogens being tested were developed by scientific teams at the non-profit International AIDS Vaccine Initiative (IAVI) and Scripps Research, and delivered via Moderna’s mRNA technology.

“While the proof-of-principle study was encouraging, it used a protein with an adjuvant to induce a response that was as was hoped — capable of neutralising and preventing infection with neutralisation of susceptible HIV strains. It did not use mRNA, but there is no reason to suppose that the mRNA that has been designed will not lead to the production of the expected protein and broadly neutralising antibodies,” leading virologist Dr Gagandeep Kang said.

The trial

The MODERNA/IAVI study is a phase 1, randomised, first-in-human, open label study to evaluate the safety and immunogenicity of the vaccines, mRNA-1644 and mRNA-1644v2-Core, in HIV-uninfected individuals. Fifty-six individuals will be randomised in four groups and safety/immunogenicity results will be available in 2023.

Burden of disease

According to the World Health Organization (WHO), HIV continues to be a major global public health issue having claimed 36.3 million lives so far. India has around 21 lakh people living with HIV and every year an estimated 68,000 new infections are added. While there is no cure for the infection, HIV infection has become a manageable chronic health condition because of increasing access to effective prevention, diagnosis, treatment and care including for opportunistic infections. However, despite decades of research, no vaccine has been developed.

The vaccine challenge

Several vaccine candidates entered clinical trials but failed, said Dr Sanjay Pujari, infectious diseases consultant closely involved in treating HIV patients. One of the challenges was to identify the correlates of immune protection. Previous vaccine studies in HIV have shown that antibodies produced were either ineffective or partially effective, and contributed to failure of trials.

Over the last decade, studies have narrowed down on bNAbs that are more potent than reactive antibodies produced after HIV infection. “These bNAbs can overcome the genetic variability of HIV by targeting the conserved regions of the envelope protein – can penetrate the `glycan shield’ that HIV uses to shield its envelope protein,” Dr Pujari said.

In naturally acquired HIV infection, only a small proportion of individuals produces bNAbs. By that time, it is quite late to have any impact on the natural course of HIV infection. So, the key is to use it as treatment (early on during acute HIV infection) or prevention. |The closest positive effectiveness was achieved in the THAI (RV144) trial i.e. around 30%. Recently, Johnson & Johnson’s vector platform vaccine trial in South Africa (Imbokodo) was stopped due to disappointing results. Hence an mRNA platform to deliver immunogens capable of inducing bNAbs is promising technology that needs to be explored in trials,” Dr Pujari said.

Early days yet

Results from this phase 1 study will dictate the future of this platform for HIV vaccine development. “This is a start and we do not know how it will go, but we hope that using good science will move us further along,” Dr Kang said.

According to Dr K Madan Gopal, Senior Consultant-Health, NITI Aayog, “mRNA technology has a distinct advantage and the platform can be easily adapted to develop a vaccine against HIV variants. It can be designed to elicit neutralising antibodies and let’s hope for the best.”

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