More Than 100 Coronavirus Vaccines Are In The Works But Vaccines Remain Elusive For Many Diseases Weve Been Fighting For Decades
If scientists develop a SARS-CoV-2 vaccine within a year and a half, it would be a world record. The title is currently held by Maurice Hilleman, who turned his daughters throat swab into a licensed mumps prophylaxis within four years. Otherwise, preventive measures typically take a long time to develop: Measles, for example, was a nationally recognized disease in the U.S. for over 50 years before a vaccine was ready. In 1984, officials declared that an HIV vaccine would be ready for testing in two years. More than 35 years later, however, there is no HIV vaccine.
Why is it that some vaccines are harder to develop than others? Often, the answer has to do with the virus itself, and how it behaves in our bodies. Sometimes, a vaccine is not commercially viable. And in other instances, the perceived threat of an illness can prolong how long it takes to develop a way to stop it.
Do Vaccines Cause Side Effects
Any vaccine can cause side effects. Side effects from vaccines are generally minor and go away within a few days.
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After More Than 40 Years Hiv Vaccine Remains Elusive
Barouch D. Vaccine strategies for HIV-1 and COVID-19. Presented at: Conference on Retroviruses and Opportunistic Infections Feb. 12-16, 2022 .
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After more than 40 years, a vaccine against HIV remains elusive because of several significant barriers, including the complexity of the virus and shifts in focus to other infectious diseases, like COVID-19, an expert said.
“The scientific challenges in the development of a prophylactic vaccine are unprecedented in the history of vaccinology,Dan H. Barouch, MD, PhD, said Sunday during the Bernard Fields Lecture at the virtual Conference on Retroviruses and Opportunistic Infections.
Barouch, who is the director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston and William Bosworth Castle Professor of Medicine at Harvard Medical School, said 79 million people have been infected with HIV and 36 million have died since the virus was discovered.
Advances in HIV vaccine research have not met high expectations especially when compared with the success of COVID-19 vaccine development, which Barouch said began after just 41 cases and one death were reported.
In response to Barouchs lecture, we compiled a list of recent Healio stories on HIV vaccine research.
Experimental HIV vaccine unsuccessful in preventing HIV
Experimental HIV vaccine does not protect women
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What Has Been Learnt So Far About How To Produce An Effective Hiv Vaccine
Vaccine researchers have learnt much from animal studies, from investigations of people who have been exposed to HIV without becoming infected, from HIV controllers, and from clinical trials of experimental HIV vaccines.
Numerous approaches to vaccine design have been tested to learn more about how to protect against HIV and how to produce strong immune responses against HIV. Vaccine trials have investigated the following questions:
- How can a vaccine introduce HIV genes or proteins into the body safely?
- How many doses of vaccine are needed to make a strong immune response?
- Might a combination of vaccines, given in a specific sequence, produce a stronger response?
- What combination of HIV proteins produces the strongest response?
- How broad is the immune response does it work against all types of HIV?
- How long do the responses last?
The first large trial of an HIV vaccine reported results in 2003. The vaccine used in that trial, AIDSVAX, was designed to stimulate the production of antibodies against a region of an HIV surface protein, gp120. The trial found that AIDSVAX was no more effective than a placebo, or dummy vaccine, in preventing HIV infection.
Another study of a vaccine using the Ad5 vector but containing subtype B HIV proteins showed no effectiveness and an increase in the risk of HIV infection for vaccinated men after the study was unblinded. It is still unclear why the risk of infection increased in these participants.
Why Dont We Have An Hiv Vaccine After 37 Years Covid
‘The problem is not failure of government. The problem is not lack of spending.’
Smallpox has been eradicated from the face of the Earth following a highly effective, worldwide vaccination campaign. Paralytic poliomyelitis is no longer a problem in the US because of development and use of effective vaccines against the poliovirus. In current times, millions of lives have been saved because of rapid deployment of effective vaccines against COVID-19. And yet, it has been 37 years since HIV was discovered as the cause of AIDS, and there is no vaccine. Here I will describe the difficulties facing development of an effective vaccine against HIV/AIDS.
I am a professor of pathology at the University of Miami Miller School of Medicine. My laboratory is credited with the discovery of the monkey virus called SIV, or simian immunodeficiency virus. SIV is the close monkey relative of the virus that causes AIDS in humans HIV, or human immunodeficiency virus. My research has contributed importantly to the understanding of the mechanisms by which HIV causes disease and to vaccine development efforts.
HIV vaccine development efforts have come up short
Vaccines have unquestionably been societys most potent weapon against viral diseases of medical importance. When the new disease AIDS burst onto the scene in the early 1980s and the virus that caused it was discovered in 1983-84, it was only natural to think that the research community would be able to develop a vaccine for it.
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Should People With Hiv Get Vaccines
Yes. Vaccines play an important role in keeping people healthy. They protect you against serious and sometimes deadly diseases.
Vaccines are especially important for people with chronic health conditions like HIV, which can make it harder to fight off vaccine-preventable diseases like pneumococcal disease or the flu. HIV can also make it more likely that youll have serious complications from those diseases, which is why getting recommended vaccines is an important part of your overall HIV medical care.
Vaccines are very effective and they dont just protect individuals from disease. They also protect communities. When most people in a community get vaccinated and become immune to a disease, there is little chance of a disease outbreak. Eventually, the disease becomes rareand sometimes, its wiped out altogether.
When Will An Hiv Vaccine Be Available
Scientists have swung between optimism and pessimism about the chances of developing an effective vaccine over the past 30 years. Scientists were feeling more optimistic after the results of the phase I and II studies that fed into Uhambo and Imbokodo, but we are now in a period, if not of pessimism, of retrenchment.
Even if Mosaico produces positive results after 2024, it will take several years for the results to be fully analysed and submitted for regulatory approval and they will only apply to the subtype B epidemic that is predominant in Europe and the Americas. Vaccine manufacturing will need to be scaled up and money will need to be pledged by donors to pay for HIV vaccination campaigns in lower-income countries. Further studies will be needed to find out if the vaccine effective in this one clinical trial show similar efficacy in other populations.
If Mosaico fails, it will not mean that HIV vaccine research will stop. However, it may be the last vaccine candidate that elicits non-neutralising antibodies. These dont directly block viral replication but recruit an immune response that does.
The next generation of vaccine candidates will need to elicit broadly neutralising antibodies , which do directly block viral replication, or stimulate a very broad and potent T-cell response. Novel vaccines are being researched, though they are only in phase I or preclinical studies so far. You can read more about them on another page.
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However No One Has Yet Been Able To Induce These Antibodies Outside Of The Handful Of Individuals Who Can Produce Them On Their Own
The three new scientific papers suggest that it might be possible to reverse-engineer the way immune cells make BNABs.
One team of researchers constructed a very close mimic of the three-pronged structure on HIV that allows the virus to latch on to human cells. Because this structure is a crucial part of how the virus attacks and because this component has some of the few patches of DNA that do not change across the many million different strains of HIV it’s a good target for an antibody.
“HIV is a crafty virus we’ve learned that the hard way over the years,” Koff said. “But this is its achilles heel.”
With this model of the structure now in hand, the researchers hope to figure out a way to induce an antibody called VRC01, one of the BNABs originally found in Donor 45, that binds to it and prevents it from infecting human cells.
“If we can’t do that, we’re pretty unlikely to make a vaccine,” Schief said.
The two other papers showed that although immune cells in mice can make a close cousin of the VRC01 antibody, it can only bind to a small number of HIV strains. The antibody would need to undergo many more mutations brought on by further immunizations within the cell before it can consistently bind to a large enough number of HIV strains.
This would likely require multiple immunizations, each causing the antibody to further mutate until its targets are sufficiently broad. While the first step is clear, the following steps are still unknown.
Rappler Talk: The Hiv Epidemic In Ph During The Covid
So far there have been five large-scale Phase 3 vaccine efficacy trials against HIV, each at a cost of over US$100 million. The first three of these failed quite convincingly no protection against acquisition of HIV infection, no lowering of viral loads in those who did become infected. In fact, in the third of these trials, the STEP trial, there was a statistically significant higher frequency of infection in individuals who had been vaccinated.
The fourth trial, the controversial Thai RV144 trial, initially reported a marginal degree of successful protection against the acquisition of HIV infection among vaccinated individuals. However, a subsequent statistical analysis reported that there was less than a 78% chance that the protection against acquisition was real.
A fifth vaccine trial, the HVTN 702 trial, was ordered to confirm and extend the results of the RV144 trial. The HVTN702 trial was halted early because of futility. No protection against acquisition. No lowering of viral load. Ouch.
The complexity of HIV
What is the problem? The biological properties that HIV has evolved make development of a successful vaccine very, very difficult. What are those properties?
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Testing Hiv Vaccine Candidates
To date, there have been only a handful of clinical trials to test the efficacy of potential HIV vaccines in people. Of the six trials that scientists saw to completion, only one vaccine candidate proved effective at preventing infection.
That lone successful trial, known as RV144, used a prime-boost strategy in which participants received a total of six shots. The four prime jabs contained a canarypox virus that is incapable of replicating in cells and carries the genetic instructions for select HIV proteins. The participants cells make those viral proteins and develop an immune response against them.
Then participants also received two boosts, an injection of an HIV protein fragment that is essential for the virus to enter cells. The hope was that participants would develop a strong, wide-ranging immune response, giving those people broad protection against a variety of HIV subtypes.
Ultimately, that vaccine strategy lowered the risk of infection by 31.2 percent in vaccinated participants compared with the unvaccinated group. Although the shot showed only modest efficacy, those results changed the field by homing in on what type of immune response people needed to prevent infection, Zolla-Pazner says.
Superstition And Science Denial
Science has made considerable progress in understanding, treating, and preventing HIV/AIDS. But it has had to fight superstition and science denial every step of the way. There are still those who claim that poverty, not HIV, is the cause of AIDS, that anti-retroviral drugs are poisons, and that HIV tests are flawed. All kinds of untested, ineffective remedies have been proposed the infamous Dana Ullman even recommends homeopathy for AIDS. These people ignore the evidence or try to explain it away, sometimes with fatal results, as in the case of Christine Maggiore, who refused anti-retroviral treatment for herself and her 3-year-old daughter. They both died of AIDS. Herbal remedies have been used in place of effective drugs. Hundreds of thousands of South Africans died unnecessarily because science denial influenced public policy: the health minister, Dr. Manto Tshabalala-Msimang was an AIDS denialist who promoted dietary measures like lemons, garlic, and olive oil and denied effective drugs to patients in South Africa. She was known as Dr. Beetroot for one of her dietary AIDS cures.
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The Latest Strategies Induce A Variety Of Defenses To Attack The Swarm Of Hiv Strains
Several current vaccine experiments aim to use a series of inoculations to stimulate the immune system to produce antibodies that can potentially block HIV infection.
IAVI-Moderna: The vaccines in this trial train certain types of B-cells as part of a strategy to produce a wide variety of antibodies against common forms of the virus, explains Taylor at the Long School of Medicine. To do this, the vaccine delivers immunogens that induce the B-cells to start the process of developing antibodies called bnAbs .
The trial will involve 56 volunteers at four sites, IAVI reports. It is a phase 1 trial, which focuses largely on safety and determining dosage levels.
A critical element is how the vaccines are delivered. The initial inoculation will be followed by several boosters, which differ from typical boosters in that they are not a repeat of the same substance, Taylor says. Instead, each booster contains a different mix of immunogens to guide the B-cells to make more bnAbs against more versions of the virus.
The idea is to get a diverse set of antibodies in people before HIV tries to infect them, says Jeffrey Bethony, PhD, professor in the GW Vaccine Research Unit at George Washington University and a researcher on the trial of the IAVI-Moderna vaccines at that site.
You need this stronger helper cell response to make broadly neutralizing antibodies, says Weissman of PSOM, a co-author on the study.
Hvtn 097 Phase 1b Vaccine Trial
The first vaccine concept tested by HVTN based on the RV144 concept was the HVTN 097 trial , which was a randomized, controlled, double-blind phase 1b study done in South Africa . The trial was designed to assess the safety and immunogenicity of the vaccine regimen in healthy, HIV-uninfected South African adults. The regimen consisted of two prime doses of the experimental canarypox HIV vaccine ALVAC-HIV followed by two booster shots of the AIDSVAX B/E. Study participants were randomized into three groups, in a 3:1:1 ratio, to receive the vaccine combined with tetanus and hepatitis B immunizations, the vaccine only or placebo. The tetanus and hepatitis B immunizations were included to assess possible cross-correlates of immune responses to HIV vaccine, however no significant differences in HIV immune responses were observed indicating that subsequent results were solely due to immune responses to HIV . The prime-boost vaccine regimen induced mostly Env-specific CD4+ T cell responses at significantly higher levels compared to RV144 vaccine recipients . IgG antibodies recognizing the V1V2 region and the IgG3 binding antibody responses to both gp120 and V1V2 antigens were also significantly higher among HVTN 097 vaccine recipients relative to RV144 recipients. ADCC antibody responses were also higher in HVTN 097 than in RV144, 72.6% and 58.5% , respectively. These favourable results provided compelling rationale for conducting larger clinical trials in South Africa .
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Vax003 And Vax004 Efficacy Trials
1994 saw the emergence of two possible vaccine candidates that were used in efficacy trials. These vaccine concepts were advanced to efficacy trials because they conferred protection to chimpanzees following HIV challenge and were safe and immunogenic in phase 1/2 clinical trials in humans . The first two efficacy trials were carried out, from 1998 to 2003, by VaxGen in North America and Thailand . Based on the knowledge gained regarding genetic variability of HIV strains and the ability to use various co-receptors, the two initial candidate HIV vaccines were redesigned as bivalent gp120 vaccines for the North American trial and for the Thailand trial . The two redesigned gp120 vaccines were derived from R5 and X4 strains . The VAX004 efficacy trial recruited 5417 volunteers who were mainly men who have sex with men in North America, and the VAX003 trial recruited 2545 volunteers comprising intravenous injection drug users in Bangkok, Thailand. Unfortunately, in 2003, data analysis revealed that the two vaccines did not prevent HIV acquisition and did not ameliorate disease .
Major Scientific Hurdles In Hiv Vaccine Development: Historical Perspective And Future Directions
- 1KwaZulu-Natal Research Institute for Tuberculosis and HIV , Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa
- 2Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA, United States
Following the discovery of HIV as a causative agent of AIDS, the expectation was to rapidly develop a vaccine but thirty years later, we still do not have a licensed vaccine. Progress has been hindered by the extensive genetic variability of HIV and our limited understanding of immune responses required to protect against HIV acquisition. Nonetheless, valuable knowledge accrued from numerous basic and translational science research studies and vaccine trials has provided insight into the structural biology of the virus, immunogen design and novel vaccine delivery systems that will likely constitute an effective vaccine. Furthermore, stakeholders now appreciate the daunting scientific challenges of developing an effective HIV vaccine, hence the increased advocacy for collaborative efforts among academic research scientists, governments, pharmaceutical industry, philanthropy, and regulatory entities. In this review, we highlight the history of HIV vaccine development efforts, highlighting major challenges and future directions.
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