Smallpox has been completely eradicated by highly effective global vaccination campaigns. Thanks to the development of an effective vaccine against poliovirus, the disease is no longer a problem in most countries. Today, rapid deployment of vaccines against COVID-19 has saved millions of lives. But, inexplicably and regrettably, 37 years have passed since HIV was discovered to be the cause of AIDS, and no effective preventive vaccine has been developed.
What exactly is the problem? A series of failed vaccine trials, long road to eradicating AIDS! On August 31st Johnson & Johnson announced that its HIV vaccine (HVTN 705/HPX2008) had failed in its first major trial, giving science another setback in its fight against HIV. It took four years, but it was only 25.2 percent effective. The $104 million trial ended early.
J&j shares fell 0.31% on the day of the announcement. While NIAID Director Anthony Fauci spoke positively of the trial’s empirical value, one of the few major HIV vaccine candidates in late-stage trials has failed. Trials of a number of highly anticipated HIV vaccines have been halted after they proved hopeless.
In 2007, the STEP (HVTN 502) study found that the vaccine may increase the risk of immune cells being infected with HIV. The HVTN 505 study, launched in 2009, failed in 2017 because the vaccine failed to stop HIV transmission or reduce viral load. In the same year, a Thai-AMERICAN RV144 trial showed that those who got the vaccine reduced their risk of HIV infection for a short time by 60% compared with those given a placebo, but the protection was compromised within a year and the vaccine was not recommended for promotion.
In 2020, a phase iii trial of THE HIV vaccine HVTN 702, developed by Sanofi and GSK, also showed little difference between placebo and vaccine. The study was even ranked by FiercePharma as the world’s top 10 clinical trial failures for 2020. The biggest reason for the failure of HIV vaccine trials is the high diversity of virus strains caused by mutations in the HIV genome.
Some say HIV is not actually a virus, it’s more like 50 million different viruses. Many strains of the virus already exist worldwide, and new ones are emerging all the time. This could mean that antibodies that target spikes in one viral subtype would not be effective against another.
Additionally, HIV is better at hiding its surface glycoproteins (HIV ENV) than the Novel Coronavirus, allowing it to enter cells more easily and cleverly “trick” the immune system. So will an HIV vaccine ever be developed? Can HIV’s elusive spell be broken? MRNA technology next? The successful development and revenue of the COVID-19 mRNA vaccine has pharmaceutical companies eager to try this technology.
On August 19, Moderna launched a human clinical trial of an HIV mRNA vaccine that is expected to end in spring 2023. Moderna currently has two HIV vaccine candidates, mrNA-1644 and mrNA-1644V2-Core. Both have been tested for safety before being used in human trials.
By injecting RNA sequences from the virulent genome into the body, mRNA vaccines produce the required viral proteins directly in the body, stimulating an immune response and preventing viral infection, skipping the process of producing proteins in the lab. In general, mRNA vaccines work by injecting aN mRNA containing the protein encoding the antigen into the body, entering the cell, translating the antigen protein, presenting it to the cell surface, or secreting it out of the cell to initiate an immune response.
MRNA vaccines have many advantages over traditional vaccines. Because it does not contain any real virus parts, there is no potential risk of infection or insertion mutation, making it relatively safe. It is also relatively fast in development and manufacturing due to high flexibility and efficient in-body delivery.
It is important to note, however, that HIV is still very different from SARS-COV-2, the virus that causes COVID-19. While HIV infects a patient’s T-cells, immune cells that fight viruses and other pathogens, SARS-COV-2 mainly infects respiratory cells. Although the mRNA technology may hold promise for an HIV vaccine, its ultimate efficacy will have to be tested.
An exciting step: therapeutic vaccines
AELIX Therapeutics has developed a novel immunogen (HIVACAT T, HTI) for use as a therapeutic HIV vaccine to help control viral replication in people already infected with HIV.
In March, AELIX reported results from the first phase I/II randomized trial of the vaccine in humans, showing that about 40% of recipients were able to dispense with antiviral therapy for several months. Although all participants experienced some level of viral rebound, five vaccinated participants maintained viral load of less than 2000 copies /ml during the 24-week analysis treatment interruption.
HTI vaccines are designed to induce specific immune responses associated with virus control, which is superior and can control the virus after the interruption of antiretroviral therapy. Current studies have established that CD4 and CD8 cells’ immune response to specific regions of HIV is related to virus control. Changes in these regions disrupt the virus’s ability to replicate, so they vary little from virus to virus, making them reliable targets for vaccine-induced T-cell responses.
However, it is important to note that the goal of any HIV cure strategy is to achieve viral load of less than 200 copies/ml without antiviral therapy. The current results are a long way from changing the current clinical application of HIV management, but may hold promise in future combination therapy strategies.
The market is huge, billions of dollars of fruit to be harvested
Research on HIV vaccine/AIDS has not received as much media attention in the past two years due to the COVID-19 pandemic, but that doesn’t mean it’s not important. In 2020, an estimated 38 million people worldwide were living with HIV (including 1.8 million children), 1.5 million were newly infected, and 680,000 people died from AIDS-related illnesses, according to UNAIDS. Between 2010 and 2015, the world spent more than $500 billion on care, treatment or prevention.
But in the 11-year period from 2009 to 2019, only $8.5 billion was spent on HIV vaccine research and development, or about $800 million a year. In just 11 months in 2020, $103.8 billion was spent globally on COVID-19 vaccine development, more than 10 times the amount allocated to HIV research and development in 11 years.
Ignoring HIV vaccine research means the risk of transmission increases dramatically.So what is the market potential for AN AIDS vaccine? Can successful r&d be richly rewarded? As early as 2004, Shao Yiming, chief expert of the AIDS Prevention and Control Center of the Chinese CDC, estimated the total market demand for AIDS vaccine, and believed that China would have a huge market of more than 30 billion yuan.
In addition, he also said that UNAIDS has decided that the first successful AIDS vaccine will also be applied to children around the world, so it is estimated that the potential market size will reach 100 billion yuan.
The global vaccine market reached $41 billion in 2020. The four vaccine giants GSK, MSD, Pfizer and Sanofi together account for 90% of the global market. The r&d pipeline layout of the four major vaccines all involves THE DIRECTION of HIV vaccine.
Whoever wins the first successful AIDS vaccine will quickly dominate the 100 billion dollar market. In general, both at home and abroad, anti-HIV drugs have a market prospect to be developed, and its vast market space is still to be explored. But there are undeniably many challenges along the way. Still, the researchers aren’t giving up.
Despite the failure of HVTN 705/HPX2008, J&J will continue to conduct phase iii trials of another HIV vaccine, HVTN 706/HPX3002, in Europe and the United States, said Paul Stoffels, j&J’s chief scientific officer. The study focused on a different group of vulnerable people, and the strains of HIV prevalent in Europe and America differ from those in Africa. The trial is expected to be completed by March 2024. We’ll see!