In 1981, AIDS first presented itself to medical literature in an article from the CDC describing a rare case of lung infection. Two of the five patients studied were dead by the time the report was released and the other three died soon afterwards.

By this time, the disease was referred to by its presenting symptom, Pneumocystis carinii pneumonia or PCP. Later an aggressive cancer, Kaposi's Sarcoma (KS), became known along with PCP not as "cancer" or "pneumonia" but "gay cancer" and "gay pneumonia" respectively.

By 1982, the illness was better understood as an immunodeficiency (ID), but public nomenclature was not ready to identify AIDS as anything other than a kind of gay disease. Before receiving its final classification we now globally recognize from an article from the CDC, the epidemic was briefly labeled as "GRID" or Gay-Related Immunodeficiency as reported in the New York Times four months earlier.

On April 23, 1984, Secretary of Health and Human Services Margaret Heckler announced to the world the AIDS vaccine would be available within two years. To this day, there has been no successful development of an HIV vaccine. As of 2018, AIDS has claimed 32 million lives and 37.9 million still live with HIV/AIDS today.

In this video from Vanity Fair, we see firsthand the handling of the Regan administration at the start of the AIDS epidemic. The press pool and staff laugh at a reporter's question about the impending death of the growing cases of AIDS. Press Secretary Larry Speakes through laughter: "I don't have it, do you?" In a separate press conference two years later when AIDS had claimed more than 4,000 lives, we hear Speakes joking about "fairies." This clip comes from a documentary by Scott Calonico called When AIDS Was Funny.

In 1963, a couple decades prior to Heckler's perplexing announcement, acclaimed vaccinologist Maurice Hilleman swabbed his own daughter's throat and developed the Measles, Mumps, and Rubella (MMR) vaccine. That vaccine set the record for development time that still holds today: Four years.

Today, the world is watching COVID-19, a disease caused by a strain of the Coronavirus. Also called SARS-CoV-2, the virus first showed infection in the United States in February of 2020, although some estimates suggest infection may have started earlier. As the disease reaches nearly every country in the world, a massive response is underway to produce a vaccine. Among several vaccine manufacturers who are already testing the vaccine in humans, we can expect the first vaccines to arrive at the end of this year, roughly 12 months from its appearance in the west and less than two years from its original manifestation in Wuhan, China.

It has been nearly 40 years since that article on PCP and still there is no vaccine for HIV. Is the rapid pace of this virus a chilling unraveling of our denegration of homosexuals?

How did we get here?

Jeffrey E. Harris, a professor of economics at the Massachusetts Institute of Technology (MIT) asked this question in 2009. In short, the answer is more complicated than the morbid complacency with victims of AIDS in the 80s, continuing to today.

HIV immunity is elusive

At the very start, the virus eluded vaccination efforts in its ability to thwart traditional vaccination strategies. The typical vaccine is designed to make our own immune system recognize the outer layer of the virus, known as the viral envelope, and subsequently destroy it. This approach proved an immediate failure in developing immunity.

Vaccines can be designed to use killed as well as live but weakened (attenuated) versions of the virus. Unfortunately, neither forms of HIV retains enough of a fully live HIV particle's integrity for it to express antigens. Antigens are parts of the pathogen with which antibodies can bind for immune neutralization.

On the surface of HIV is a protein called Envelope glycoprotein 120 or just gp120. Since its discovery in 1984, gp120 was a key structure in the virus for developing a vaccine because its binding to another receptor called CD4 marked the start of infection.

gp120, a key structure on the surface of HIV once allured vaccine development efforts.

The discovery of gp120 began yet another arc of disappointment for vaccine development. The structure and chemical properties of gp120 make it very difficult for antibodies to bind and the structure can easily be shed.

We're still working on it

The history of the HIV vaccine is still being written. It is a maddening cycle of being constantly close to finally having it right, only to fall short and go back to the drawing board. For example:

In 2004, a promising vaccine called V520 was developed by the National Institute of Allergy and Infectious Diseases (NIAID). The vaccine was initially demonstrated as safe and was shown to induce immunity in more than half of participants. Then in 2007, the vaccine was put to rest when evidence surfaced of the vaccine potentially carried an increased risk of becoming infected with HIV.

In 2016 the HVTN 702 vaccine from an organization called Uhambo, widely known as the “Uhambo vaccine” was proven safe in phase IIb-III trials but ultimately failed to prove efficacious. The vaccine was stopped in this year, 2020.

The biggest misconception about the HIV vaccine is that we’ve moved on.

In fact, research and development is still very active. In 2011 alone, $845M was invested in research for an HIV vaccine.

In 1991, VaxGen, a company spun off from Genentech, gained attention for their AIDSVAX vaccine. The first two of the three phases of vaccine tests were promising. The vaccine was proven safe in animal tests and produced antibodies in a whopping 99% of humans studied. The company applied to the FDA to move into phase III trials, the final stage before releasing and distributing the vaccine. However a large percentage of the participants studied ended up becoming infected with HIV anyway despite these antibodies.

Though deemed a failure in North America, VaxGen worked on a new vaccine called RV 144 using AIDSVAX as a component and continued trials in Thailand. Ultimately the vaccine reached only 26% efficacy.

By 2015 the phase I trials of a canarypox vector (a vector is a molecular delivery tool to shuttle therapeutic genes into cells) started in 1999 in Uganda showed strong immune response and safety in participants.

Why is it different with the COVID-19 vaccine?

The UK vaccine manufacturer AstraZeneca predicts they'll have 30M doses of their COVID-19 vaccine by September of this year...in just three months from now, with 100M additional doses becoming available by the end of the year. Earlier this week, the company announced an additional 400M vaccines throughout Europe and 1B vaccines in developing nations by the end of the year.. The company is so confident in their vaccine which is still in clinical testing, they've already started producing it.

See our vaccine timetable where we track key events, past, present, and future for development of the COVID-19 vaccine.

In fact, there are so many COVID-19 vaccines being produced globally right now, concern has shifted to whether or not we'll have enough glass vials to contain them in time.

Antibodies

A simplified diagram of an antibody

As a quick refresher, antibodies are key molecular structures in the immune system which bind to parts of pathogens like puzzle pieces. When an antibody binds to one of these locations, the pathogen is considered antigenic, and is called an antigen. If these antibodies are successful in subsequently destroying or hampering the pathogen's deleterious effects, they are called neutralizing antibodies.

Unlike in HIV, individuals infected by COVID-19 have recovered and as a result have produced neutralizing antibodies. There is still more data to gather to understand how robust this immunity is and whether antibodies produced by the vaccines will remain neutralizing long term. However, if our bodies can produce antibodies which successfully neutralize the virus, it becomes a matter of replicating them in a vaccine.

Is anyone immune to HIV?

In 1982, a New Yorker named Jerry Green was among the first to succumb to AIDS. However, his boyfriend Stephen Crohn had no symptoms. In 1994, the great-nephew of Crohn disease's namesake was discovered to be the first person resistant to AIDS. Crohn was born with the gift of the delta-32 (Δ32) mutation which alters the CCR5 receptor.

The CCR5 receptor appears on the surface of white blood cells. Thomas Splettstoesser (www.scistyle.com) / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0)

Δ32 probably saved Crohn's life. The mutation causes a mutation in the structure on the white blood cells called CCR5. This mutation prevents infection by certain strains of HIV. Crohn had several partners with this strain including his boyfriend. Despite this extraordinary stroke of luck, Crohn's gift was his curse, watching his friends die rapidly around him. He committed suicide by drug overdose at 66.

The long, four part blue molecule on the far left is CD4. CCR5 appears next to it. On the right, we see how these molecules are used together by HIV to bind to cells.

As it happens, there is a small percentage of the population which is at least partially resistant to HIV, about 10%. Some have the same mutation as Crohn. Unfortunately, this is not a discovery that can be scooped up and administered in a vaccine, but it does turn our attention to thwarting the virus through genetics.

Antiretroviral therapy (ART) has slowed the progression of HIV in many patients, but modern science is looking to gene therapy, a means of delivering DNA building blocks into cells in order to create beneficial changes to our DNA. One such treatments, maraviroc (MVC), was successful enough when used with ART that it is currently the only CCR5-binding AIDS treatment to be approved in the US, Canada, and Europe.

Photo Credit: "Volunteering-Working with AIDS victims" by Kathy McGraw is licensed under CC BY 2.0.