Tag Archives: Infectious diseases

Anthony Fauci’s enduring impact on the AIDS crisis

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After 38 years as the head of the National Institute of Allergy and Infectious Diseases, Dr. Anthony Fauci announced on Monday that he will be stepping down from his role in December. Appointed to the position in 1984 by then-president Ronald Reagan, Fauci has personally overseen the federal government’s response to some of the 20th century’s deadliest infectious diseases — from tuberculosis and COVID to SARS and MERS.

But, as he told The Guardian in 2020, “my career and my identity has really been defined by HIV.” The prevention and treatment of HIV has been a prioritized area of research for the NIAID since 1986, and one that Dr. Fauci has devoted much of his public service to. The current state of AIDS research and response in America is thanks in no small part to his continued efforts in the field.

The NIAID is one of 27 specialized institutes and centers that make up the National Institutes of Health (NIH), which in turn reports to the Department of Health and Human Services. The NIH overall serves as the federal government’s premiere health research program. The NIAID operates within that bureaucratic framework, conducting and supporting “basic and applied research to better understand, treat, and ultimately prevent infectious, immunologic, and allergic diseases,” per its mission statement. That includes everything from working to mitigate effects of the annual influenza strain and alleviate asthma in urban youth to leading the development of an effective vaccine against COVID-19. The technology behind that vaccine is now being adapted for use against HIV and malaria as well.

Working at the forefront of immunoregulation research in the early 1980s, Fauci developed treatments for a class of otherwise-fatal inflammatory diseases including polyarteritis nodosa, granulomatosis with polyangiitis (formerly Wegener's granulomatosis) and lymphomatoid granulomatosis. The results of those studies helped lay the groundwork for today’s research by the NIAID’s Laboratory of Immunoregulation. That research includes cellular and molecular mechanisms of HIV immunopathogenesis and the treatment of immune-mediated diseases. Combining the institute’s nearly four decades of HIV/AIDS research with cutting edge genomic technology has brought us not one, but three potentially viable AIDS vaccines, all of which are currently in clinical trials.

“Finding an HIV vaccine has proven to be a daunting scientific challenge,” Dr. Fauci said in a March NIAID release. “With the success of safe and highly effective COVID-19 vaccines, we have an exciting opportunity to learn whether mRNA technology can achieve similar results against HIV infection.”

The active, hands-on approach we see in response to the AIDS epidemic today is a far cry from that of the Reagan administration at the start of the crisis in 1983, which initially met the issue with silence. That is, outside of the time Larry Speakes, Reagan's press secretary, called it “the gay plague.”

Fauci’s initial efforts during the AIDS epidemic did more harm than good. In 1983, he published The Acquired Immune Deficiency Syndrome: The Ever-Broadening Clinical Spectrum in which he warned of “the possibility that routine close contact, as within a family household, can spread the disease.” We know now that this is not at all how HIV works, but at the time — despite the study urging caution until more evidence was gathered — it set off a moral panic in the media. The study was subsequently picked up by right-wing organizations and used as a political cudgel blaming the LGBTQIA+ community for the disease.

Reagan himself didn’t publicly mention the crisis until 1985, three years after it was officially identified by the CDC (and, coincidentally, a month after he admitted his involvement in the Iran-Contra Scandal). Social stigma around the disease made funding for basic health research nearly impossible to acquire, and was exacerbated by Reagan’s repeated budget cuts to the NIH and CDC.

"The inadequate funding to date has seriously restricted our work and has presumably deepened the invasion of this disease into the American population," a CDC staffer wrote in an April, 1983 memo to then-Assistant Director, Dr. Walter Dowdle. "In addition, the time wasted pursuing money from Washington has cast an air of despair over AIDS workers throughout the country."

Even after his appointment as Chief Medical Officer — one who was determined to treat the AIDS crisis with its deserved gravity — Fauci faced pushback from the LGBTQIA+ community, who demanded greater action from the government in response to the crisis and sought to accelerate the glacial pace of drug trials at the time.

By 1990, the community’s patience had reached a breaking point, resulting in ACT UP’s (AIDS Coalition to Unleash Power) attempt to storm the NIH in protest. “One of the things that people in ACT UP said is that we are the people who are experiencing this novel disease, and we are the experts, not just the scientists and doctors,” Garance Ruta, executive director of GEN magazine and an ACT UP member at the protest, told The Washington Post in 2020.

“I was trying to get them into all the planning meetings for the clinical trials,” Fauci told WaPo, in response. “I felt very strongly that we needed to get them into the planning process because they weren’t always right, but they had very, very good input.”

Over the last 30 years, the NIH has helped lead development of numerous antiretroviral therapies. Azidothymidine (AZT), the first drug discovered to inhibit HIV’s replication without damaging cells, was initially developed by the NIH as an anti-cancer drug in the 1960s. Its use as an antiretroviral, approved by the FDA in 1987, helped to establish the AIDS Clinical Trials Group (ACTG), which further accelerated research into nucleoside reverse transcriptase inhibitors (NRTIs, the class of drug to which AZT belongs). NIAID-funded studies in the 1990s helped establish combination therapies, which combine multiple medications for a synergistic effect, and explored a newly-identified class of drug, non-nucleoside reverse transcriptase inhibitors or NNRTIs.

HIV pill count
NIAID

Today, nearly three dozen antiretroviral drugs are available, many of them combined into fixed-dose tablets. In the 1990s, people living with AIDS would be expected to take up to 20 individual pills at set schedules throughout the day. The average lifespan for someone infected with the disease was roughly a year. Today, assuming you’re lucky enough to live in the developed world, AIDS has become a chronic condition to be controlled with a single daily pill. For the 20 million people living with AIDS but without access to modern treatment, it remains a death sentence.

The state of medical research technology has also evolved, even if the nation’s prevailing notions of fairness and equality haven't improved much in the intervening years since Reagan held power. Advances in laboratory standardization and automation have rapidly reduced development cycles and the occurrence of outlier results. The monotonous tasks that were once performed by lab assistants are now handled by robotic arms equipped with pipette arrays.

Disease prevention and diagnosis efforts have been augmented in recent years with artificial intelligence and machine learning algorithms. They’ve also found use in helping to stem the spread of HIV and improve access to both retrovirals and PReP with applications including, “ML with smartphone-collected and social media data to promote real-time HIV risk reduction, virtual reality tools to facilitate HIV serostatus disclosure, and chatbots for HIV education,” argue Drs. Julia Marcus and Whitney Sewell, of Harvard and UMass Amherst, respectively.

And just as Dr Fauci is, quite specifically, not retiring — “I want to use what I have learned as NIAID Director to continue to advance science and public health and to inspire and mentor the next generation of scientific leaders as they help prepare the world to face future infectious disease threats,” he noted in Monday’s announcement — the work of the NIAID is far from complete. Even as we slowly conquer existing scourges like COVID and HIV, re-emerging threats like Monkeypox (not to mention ancient killers like Polio) will continue to appear on our quickly warming planet.

Anthony Fauci’s enduring impact on the AIDS crisis

Posted on by

After 38 years as the head of the National Institute of Allergy and Infectious Diseases, Dr. Anthony Fauci announced on Monday that he will be stepping down from his role in December. Appointed to the position in 1984 by then-president Ronald Reagan, Fauci has personally overseen the federal government’s response to some of the 20th century’s deadliest infectious diseases — from tuberculosis and COVID to SARS and MERS.

But, as he told The Guardian in 2020, “my career and my identity has really been defined by HIV.” The prevention and treatment of HIV has been a prioritized area of research for the NIAID since 1986, and one that Dr. Fauci has devoted much of his public service to. The current state of AIDS research and response in America is thanks in no small part to his continued efforts in the field.

The NIAID is one of 27 specialized institutes and centers that make up the National Institutes of Health (NIH), which in turn reports to the Department of Health and Human Services. The NIH overall serves as the federal government’s premiere health research program. The NIAID operates within that bureaucratic framework, conducting and supporting “basic and applied research to better understand, treat, and ultimately prevent infectious, immunologic, and allergic diseases,” per its mission statement. That includes everything from working to mitigate effects of the annual influenza strain and alleviate asthma in urban youth to leading the development of an effective vaccine against COVID-19. The technology behind that vaccine is now being adapted for use against HIV and malaria as well.

Working at the forefront of immunoregulation research in the early 1980s, Fauci developed treatments for a class of otherwise-fatal inflammatory diseases including polyarteritis nodosa, granulomatosis with polyangiitis (formerly Wegener's granulomatosis) and lymphomatoid granulomatosis. The results of those studies helped lay the groundwork for today’s research by the NIAID’s Laboratory of Immunoregulation. That research includes cellular and molecular mechanisms of HIV immunopathogenesis and the treatment of immune-mediated diseases. Combining the institute’s nearly four decades of HIV/AIDS research with cutting edge genomic technology has brought us not one, but three potentially viable AIDS vaccines, all of which are currently in clinical trials.

“Finding an HIV vaccine has proven to be a daunting scientific challenge,” Dr. Fauci said in a March NIAID release. “With the success of safe and highly effective COVID-19 vaccines, we have an exciting opportunity to learn whether mRNA technology can achieve similar results against HIV infection.”

The active, hands-on approach we see in response to the AIDS epidemic today is a far cry from that of the Reagan administration at the start of the crisis in 1983, which initially met the issue with silence. That is, outside of the time Larry Speakes, Reagan's press secretary, called it “the gay plague.”

Fauci’s initial efforts during the AIDS epidemic did more harm than good. In 1983, he published The Acquired Immune Deficiency Syndrome: The Ever-Broadening Clinical Spectrum in which he warned of “the possibility that routine close contact, as within a family household, can spread the disease.” We know now that this is not at all how HIV works, but at the time — despite the study urging caution until more evidence was gathered — it set off a moral panic in the media. The study was subsequently picked up by right-wing organizations and used as a political cudgel blaming the LGBTQIA+ community for the disease.

Reagan himself didn’t publicly mention the crisis until 1985, three years after it was officially identified by the CDC (and, coincidentally, a month after he admitted his involvement in the Iran-Contra Scandal). Social stigma around the disease made funding for basic health research nearly impossible to acquire, and was exacerbated by Reagan’s repeated budget cuts to the NIH and CDC.

"The inadequate funding to date has seriously restricted our work and has presumably deepened the invasion of this disease into the American population," a CDC staffer wrote in an April, 1983 memo to then-Assistant Director, Dr. Walter Dowdle. "In addition, the time wasted pursuing money from Washington has cast an air of despair over AIDS workers throughout the country."

Even after his appointment as Chief Medical Officer — one who was determined to treat the AIDS crisis with its deserved gravity — Fauci faced pushback from the LGBTQIA+ community, who demanded greater action from the government in response to the crisis and sought to accelerate the glacial pace of drug trials at the time.

By 1990, the community’s patience had reached a breaking point, resulting in ACT UP’s (AIDS Coalition to Unleash Power) attempt to storm the NIH in protest. “One of the things that people in ACT UP said is that we are the people who are experiencing this novel disease, and we are the experts, not just the scientists and doctors,” Garance Ruta, executive director of GEN magazine and an ACT UP member at the protest, told The Washington Post in 2020.

“I was trying to get them into all the planning meetings for the clinical trials,” Fauci told WaPo, in response. “I felt very strongly that we needed to get them into the planning process because they weren’t always right, but they had very, very good input.”

Over the last 30 years, the NIH has helped lead development of numerous antiretroviral therapies. Azidothymidine (AZT), the first drug discovered to inhibit HIV’s replication without damaging cells, was initially developed by the NIH as an anti-cancer drug in the 1960s. Its use as an antiretroviral, approved by the FDA in 1987, helped to establish the AIDS Clinical Trials Group (ACTG), which further accelerated research into nucleoside reverse transcriptase inhibitors (NRTIs, the class of drug to which AZT belongs). NIAID-funded studies in the 1990s helped establish combination therapies, which combine multiple medications for a synergistic effect, and explored a newly-identified class of drug, non-nucleoside reverse transcriptase inhibitors or NNRTIs.

HIV pill count
NIAID

Today, nearly three dozen antiretroviral drugs are available, many of them combined into fixed-dose tablets. In the 1990s, people living with AIDS would be expected to take up to 20 individual pills at set schedules throughout the day. The average lifespan for someone infected with the disease was roughly a year. Today, assuming you’re lucky enough to live in the developed world, AIDS has become a chronic condition to be controlled with a single daily pill. For the 20 million people living with AIDS but without access to modern treatment, it remains a death sentence.

The state of medical research technology has also evolved, even if the nation’s prevailing notions of fairness and equality haven't improved much in the intervening years since Reagan held power. Advances in laboratory standardization and automation have rapidly reduced development cycles and the occurrence of outlier results. The monotonous tasks that were once performed by lab assistants are now handled by robotic arms equipped with pipette arrays.

Disease prevention and diagnosis efforts have been augmented in recent years with artificial intelligence and machine learning algorithms. They’ve also found use in helping to stem the spread of HIV and improve access to both retrovirals and PReP with applications including, “ML with smartphone-collected and social media data to promote real-time HIV risk reduction, virtual reality tools to facilitate HIV serostatus disclosure, and chatbots for HIV education,” argue Drs. Julia Marcus and Whitney Sewell, of Harvard and UMass Amherst, respectively.

And just as Dr Fauci is, quite specifically, not retiring — “I want to use what I have learned as NIAID Director to continue to advance science and public health and to inspire and mentor the next generation of scientific leaders as they help prepare the world to face future infectious disease threats,” he noted in Monday’s announcement — the work of the NIAID is far from complete. Even as we slowly conquer existing scourges like COVID and HIV, re-emerging threats like Monkeypox (not to mention ancient killers like Polio) will continue to appear on our quickly warming planet.

Hitting the Books: How Moderna dialed-in its vaccine to fight COVID’s variants

Posted on by

The national news cycle may have largely moved on from coverage of the COVID-19 pandemic — despite, as of this writing, infections being on the rise and more than 300 deaths tallied daily from the disease. But that certainly doesn't diminish the unprecedented international response effort and warp speed development of effective vaccines. 

In The Messenger: Moderna, the Vaccine, and the Business Gamble That Changed the World, veteran Wall Street Journal reporter Peter Loftus takes readers through the harrowing days of 2020 as the virus raged across the globe and biotech startup Moderna raced to create a vaccine to halt the viral rampage. The excerpt below takes place in early 2021, as the company works to adapt its treatments to slow the surging Delta variant's spread.

Messenger Cover
Harvard Business Review Press

Reprinted by permission of Harvard Business Review Press. Excerpted from The Messenger: Moderna, the Vaccine, and the Business Gamble That Changed the World by Peter Loftus. Copyright 2022 Peter Loftus. All rights reserved.

Delta

Viruses of all types frequently change. They mutate as they jump from person to person. The coronavirus was no different. Throughout the pandemic, health officials tracked variants of the SARS CoV-2 virus first found in Wuhan, China, as those variants arose. None seemed a big concern, until one was flagged in the United Kingdom in December 2020, right as Moderna’s vaccine neared approval. This UK variant appeared to be as much as 70 percent more transmissible. It was given the name the Alpha variant.

Alpha reinforced the possibility that the virus could mutate enough to become resistant to vaccines and treatments that were designed to target the earlier, predominant strain. Or it could fizzle out. But variants would keep coming. Shortly after Alpha, researchers identified another variant circulating in South Africa. Beta.

In late December—just a few days after the United States authorized its vaccine — Moderna issued a statement that it was confident the vaccine would be effective at inducing the necessary immune response against variants. The original vaccine targeted the full length of the spike protein of the coronavirus, and the new variants appeared to have mutations in the spike protein that represented less than a 1 percent difference from the original.

“So, from what we’ve seen so far, the variants being described do not alter the ability of neutralizing antibodies elicited by vaccination to neutralize the virus,” Tal Zaks said during a virtual appearance at the all-important J.P. Morgan Healthcare Conference in January 2021. “My definition of when to get worried is either when we see real clinical data that suggest that people who’ve either been sick or have been immunized are now getting infected at significant rates with the new variants.”

Even if the vaccine proved less effective against a new variant, Moderna could use its mRNA technology to quickly tweak the design of its Covid-19 vaccine, to better target a variant of the virus, Zaks said. After all, the company and its federal health partners had already demonstrated the year before how quickly they could design, manufacture, and test a new vaccine.

Still, Moderna needed to run a series of tests to see if its original vaccine offered the same high level of protection against variants as it showed in the big Phase 3 clinical trial.

Moderna collaborated again with researchers from NIAID including Barney Graham and Kizzmekia Corbett. They analyzed blood samples taken from eight people who were vaccinated with Moderna’s shot in the Phase 1 trial back in early 2020. They essentially mixed these blood samples with the coronavirus variants, engineered so they copied the mutations of the variants but couldn’t replicate and pose a threat to lab researchers. Researchers then analyzed whether the vaccine-induced antibodies present in the human blood samples could effectively neutralize the virus variants.

The results were mixed. They suggested the vaccine worked as well against the UK Alpha variant as against the original strain of the coronavirus. That was good news. Even if the UK variant spread more easily than the original virus, Moderna’s vaccine could probably mute its effects.

But the Beta variant first identified in South Africa seemed to pose a problem. The vaccine-induced antibodies had a significantly reduced neutralization effect on this strain in the lab tests. “Oh shit,” Bancel said when Stephen Hoge showed him the data. It wouldn’t be the last time. Moderna’s leaders saw the data on a Friday in late January 2021 and spent the weekend discussing it. They hoped that a modified, variant- targeted vaccine wouldn’t be needed, and that Moderna’s original vaccine would suffice, even if it had a reduced neutralizing effect. But Moderna didn’t want to be caught flat-footed if a variant-specific booster was needed.

They decided by the next Monday it was time to take action. They would develop a new version of the vaccine, one that more closely matched the mutations seen in the strain that circulated in South Africa, and which could potentially be given as a booster shot to better protect people who had gotten the original vaccine.

“It really highlights the fact that we need to continue to stay vigilant,” Moderna’s president, Stephen Hoge, said. “This virus is evolving, it’s changing its stripes. And we need to keep testing the new variants, and make sure the vaccine works against them.”

Moderna repeated the steps it took a year earlier: it quickly designed a new variant vaccine and manufactured an initial batch for human testing, shipping it to NIAID in late February, a year to the day after it had shipped the original batch of the original vaccine. The new batch was called mRNA-1273.351, appending the “351” because researchers initially called the variant seen in South Africa “B.1.351.”

“Moderna is going to keep chasing the variants until the pandemic is under control,” Bancel said that day.

Moderna also developed other plans to test. It would try a third dose of its original vaccine, given several months after the second dose, to see if that booster shot would protect against variants. It would also develop a combined vaccine that targeted both the original strain and the Beta strain.

Once again, volunteers stepped up to test these various approaches. Neal Browning, the Microsoft engineer who was the second person to get Moderna’s vaccine, showed up once again to volunteer. In the intervening year, he had gotten married, in a small outdoor ceremony to minimize Covid risk. Now he received a third dose of the Moderna vaccine. He felt tenderness at the injection site and a low-grade fever and chills, but the symptoms went away after several hours. He continued to visit the research site to give blood samples to be analyzed for immune responses.

By early May, Moderna had some answers. It gave booster shots — either the original vaccine or the Beta variant – targeting vaccine — to people about six to eight months after they had been vaccinated with two doses of the original vaccine. The company found that in the new analysis, both types of booster shots increased neutralizing antibodies against the Beta variant. And they increased antibodies against a related variant that had been detected in Brazil. But the newer version of the vaccine that targeted Beta induced a stronger immune response against the Beta variant than the booster shot of Moderna’s original vaccine.

At the time, Moderna’s plan was to continue testing the different booster approaches, with an eye toward possibly getting government approval to sell the booster shot that specifically targeted the Beta variant. But it didn’t seem particularly urgent. The existing mass vaccination campaign was making good progress at the time.

Then, with the virus on the retreat in the United States, scientists discovered a new variant driving an alarming surge in India. This variant had already jumped to other countries, including the United States. Initially, it was code-named B.1.617.2. It was even more contagious than the Alpha variant and there were fears that it could evade vaccines. This was the Delta variant.

The previous winter the hope provided by vaccines was juxtaposed with the deadliest virus surge in the United States. Again, in early summer 2021, the lifting of mask mandates and reopening of public life was bringing great hope and a sense of relief. And again, this would be juxtaposed with public-health officials sounding the alarm about the Delta variant. It could become the dominant strain of the virus in the United States, they said. The best way to stop its spread, officials said, was to get more people vaccinated, with any of the three vaccines available.

By mid-June, about 55 percent of the US adult population was fully vaccinated, which was good but still left many people exposed to the new Delta variant that spread much more easily than earlier strains. And there were clear geographic vulnerabilities. The Northeast United States had higher vaccination rates than the national average, particularly in some New England states, like Vermont with its 62 percent vaccination rate. But in the South the numbers were much lower in states like Alabama, where only 30 percent were fully vaccinated.

The high proportions of unvaccinated people in those places would serve as a breeding ground for Delta. And the more the variant spread, the more it could mutate into more variants.

By late July, the effects of an ill-fated combination — stubbornly low vaccination rates in some regions, the winding down of masking and distancing, and a rapidly spreading Delta strain—were clearer. Infections, hospitalizations, and deaths were climbing again, especially in open states like Florida, which suffered one of the highest rates of Covid-19 hospitalizations, and low-vaccinated states.

Doctors and nurses who thought they had put the worst of the pandemic behind them were once again scrambling to treat severely ill Covid-19 patients in intensive-care units. By the end of August, the United States was averaging about fifteen hundred Covid-19 deaths a day, versus fewer than two hundred in early July. Nearly all of the patients who ended up in the ICU were unvaccinated.

Some vaccinated people were beginning to test positive for Covid-19, too — commonly called “breakthrough” cases—and a few progressed to severe cases. The vaccines, after all, weren’t 100 percent effective in the clinical trials, either. A small percentage of vaccinated people in the studies got sick with Covid. But it was becoming clear that the vaccines weren’t entirely blocking transmission of the virus or stopping asymptomatic infections, as initially hoped.

Vaccinated people were better protected than unvaccinated people, even when Delta took over. In states like Massachusetts, less than 1 percent of fully vaccinated people in the state had tested positive for Covid-19 by the fall of 2021. Other analysis showed that people who weren’t fully vaccinated were nearly five times more likely to get infected, ten times more likely to be hospitalized and eleven times more likely to die from Covid than fully vaccinated people.

But Delta reminded people, or made them understand for the first time, that the vaccines weren’t bullet-proof. New indoor mask mandates were imposed, including at schools, where educators just weeks earlier had been eager for the first normal back-to-school season in two years. No vaccine was yet authorized for children under twelve (both Moderna and Pfizer were studying that population), raising concerns that Delta would spread rapidly among them as they gathered in classrooms.

By the end of the summer, people wondered if the pandemic would ever end. Some started talking about the coronavirus as endemic, not a pandemic.

And a big slice of America was still saying “No thanks” to the vaccine.

Hitting the Books: How Moderna dialed-in its vaccine to fight COVID’s variants

Posted on by

The national news cycle may have largely moved on from coverage of the COVID-19 pandemic — despite, as of this writing, infections being on the rise and more than 300 deaths tallied daily from the disease. But that certainly doesn't diminish the unprecedented international response effort and warp speed development of effective vaccines. 

In The Messenger: Moderna, the Vaccine, and the Business Gamble That Changed the World, veteran Wall Street Journal reporter Peter Loftus takes readers through the harrowing days of 2020 as the virus raged across the globe and biotech startup Moderna raced to create a vaccine to halt the viral rampage. The excerpt below takes place in early 2021, as the company works to adapt its treatments to slow the surging Delta variant's spread.

Messenger Cover
Harvard Business Review Press

Reprinted by permission of Harvard Business Review Press. Excerpted from The Messenger: Moderna, the Vaccine, and the Business Gamble That Changed the World by Peter Loftus. Copyright 2022 Peter Loftus. All rights reserved.

Delta

Viruses of all types frequently change. They mutate as they jump from person to person. The coronavirus was no different. Throughout the pandemic, health officials tracked variants of the SARS CoV-2 virus first found in Wuhan, China, as those variants arose. None seemed a big concern, until one was flagged in the United Kingdom in December 2020, right as Moderna’s vaccine neared approval. This UK variant appeared to be as much as 70 percent more transmissible. It was given the name the Alpha variant.

Alpha reinforced the possibility that the virus could mutate enough to become resistant to vaccines and treatments that were designed to target the earlier, predominant strain. Or it could fizzle out. But variants would keep coming. Shortly after Alpha, researchers identified another variant circulating in South Africa. Beta.

In late December—just a few days after the United States authorized its vaccine — Moderna issued a statement that it was confident the vaccine would be effective at inducing the necessary immune response against variants. The original vaccine targeted the full length of the spike protein of the coronavirus, and the new variants appeared to have mutations in the spike protein that represented less than a 1 percent difference from the original.

“So, from what we’ve seen so far, the variants being described do not alter the ability of neutralizing antibodies elicited by vaccination to neutralize the virus,” Tal Zaks said during a virtual appearance at the all-important J.P. Morgan Healthcare Conference in January 2021. “My definition of when to get worried is either when we see real clinical data that suggest that people who’ve either been sick or have been immunized are now getting infected at significant rates with the new variants.”

Even if the vaccine proved less effective against a new variant, Moderna could use its mRNA technology to quickly tweak the design of its Covid-19 vaccine, to better target a variant of the virus, Zaks said. After all, the company and its federal health partners had already demonstrated the year before how quickly they could design, manufacture, and test a new vaccine.

Still, Moderna needed to run a series of tests to see if its original vaccine offered the same high level of protection against variants as it showed in the big Phase 3 clinical trial.

Moderna collaborated again with researchers from NIAID including Barney Graham and Kizzmekia Corbett. They analyzed blood samples taken from eight people who were vaccinated with Moderna’s shot in the Phase 1 trial back in early 2020. They essentially mixed these blood samples with the coronavirus variants, engineered so they copied the mutations of the variants but couldn’t replicate and pose a threat to lab researchers. Researchers then analyzed whether the vaccine-induced antibodies present in the human blood samples could effectively neutralize the virus variants.

The results were mixed. They suggested the vaccine worked as well against the UK Alpha variant as against the original strain of the coronavirus. That was good news. Even if the UK variant spread more easily than the original virus, Moderna’s vaccine could probably mute its effects.

But the Beta variant first identified in South Africa seemed to pose a problem. The vaccine-induced antibodies had a significantly reduced neutralization effect on this strain in the lab tests. “Oh shit,” Bancel said when Stephen Hoge showed him the data. It wouldn’t be the last time. Moderna’s leaders saw the data on a Friday in late January 2021 and spent the weekend discussing it. They hoped that a modified, variant- targeted vaccine wouldn’t be needed, and that Moderna’s original vaccine would suffice, even if it had a reduced neutralizing effect. But Moderna didn’t want to be caught flat-footed if a variant-specific booster was needed.

They decided by the next Monday it was time to take action. They would develop a new version of the vaccine, one that more closely matched the mutations seen in the strain that circulated in South Africa, and which could potentially be given as a booster shot to better protect people who had gotten the original vaccine.

“It really highlights the fact that we need to continue to stay vigilant,” Moderna’s president, Stephen Hoge, said. “This virus is evolving, it’s changing its stripes. And we need to keep testing the new variants, and make sure the vaccine works against them.”

Moderna repeated the steps it took a year earlier: it quickly designed a new variant vaccine and manufactured an initial batch for human testing, shipping it to NIAID in late February, a year to the day after it had shipped the original batch of the original vaccine. The new batch was called mRNA-1273.351, appending the “351” because researchers initially called the variant seen in South Africa “B.1.351.”

“Moderna is going to keep chasing the variants until the pandemic is under control,” Bancel said that day.

Moderna also developed other plans to test. It would try a third dose of its original vaccine, given several months after the second dose, to see if that booster shot would protect against variants. It would also develop a combined vaccine that targeted both the original strain and the Beta strain.

Once again, volunteers stepped up to test these various approaches. Neal Browning, the Microsoft engineer who was the second person to get Moderna’s vaccine, showed up once again to volunteer. In the intervening year, he had gotten married, in a small outdoor ceremony to minimize Covid risk. Now he received a third dose of the Moderna vaccine. He felt tenderness at the injection site and a low-grade fever and chills, but the symptoms went away after several hours. He continued to visit the research site to give blood samples to be analyzed for immune responses.

By early May, Moderna had some answers. It gave booster shots — either the original vaccine or the Beta variant – targeting vaccine — to people about six to eight months after they had been vaccinated with two doses of the original vaccine. The company found that in the new analysis, both types of booster shots increased neutralizing antibodies against the Beta variant. And they increased antibodies against a related variant that had been detected in Brazil. But the newer version of the vaccine that targeted Beta induced a stronger immune response against the Beta variant than the booster shot of Moderna’s original vaccine.

At the time, Moderna’s plan was to continue testing the different booster approaches, with an eye toward possibly getting government approval to sell the booster shot that specifically targeted the Beta variant. But it didn’t seem particularly urgent. The existing mass vaccination campaign was making good progress at the time.

Then, with the virus on the retreat in the United States, scientists discovered a new variant driving an alarming surge in India. This variant had already jumped to other countries, including the United States. Initially, it was code-named B.1.617.2. It was even more contagious than the Alpha variant and there were fears that it could evade vaccines. This was the Delta variant.

The previous winter the hope provided by vaccines was juxtaposed with the deadliest virus surge in the United States. Again, in early summer 2021, the lifting of mask mandates and reopening of public life was bringing great hope and a sense of relief. And again, this would be juxtaposed with public-health officials sounding the alarm about the Delta variant. It could become the dominant strain of the virus in the United States, they said. The best way to stop its spread, officials said, was to get more people vaccinated, with any of the three vaccines available.

By mid-June, about 55 percent of the US adult population was fully vaccinated, which was good but still left many people exposed to the new Delta variant that spread much more easily than earlier strains. And there were clear geographic vulnerabilities. The Northeast United States had higher vaccination rates than the national average, particularly in some New England states, like Vermont with its 62 percent vaccination rate. But in the South the numbers were much lower in states like Alabama, where only 30 percent were fully vaccinated.

The high proportions of unvaccinated people in those places would serve as a breeding ground for Delta. And the more the variant spread, the more it could mutate into more variants.

By late July, the effects of an ill-fated combination — stubbornly low vaccination rates in some regions, the winding down of masking and distancing, and a rapidly spreading Delta strain—were clearer. Infections, hospitalizations, and deaths were climbing again, especially in open states like Florida, which suffered one of the highest rates of Covid-19 hospitalizations, and low-vaccinated states.

Doctors and nurses who thought they had put the worst of the pandemic behind them were once again scrambling to treat severely ill Covid-19 patients in intensive-care units. By the end of August, the United States was averaging about fifteen hundred Covid-19 deaths a day, versus fewer than two hundred in early July. Nearly all of the patients who ended up in the ICU were unvaccinated.

Some vaccinated people were beginning to test positive for Covid-19, too — commonly called “breakthrough” cases—and a few progressed to severe cases. The vaccines, after all, weren’t 100 percent effective in the clinical trials, either. A small percentage of vaccinated people in the studies got sick with Covid. But it was becoming clear that the vaccines weren’t entirely blocking transmission of the virus or stopping asymptomatic infections, as initially hoped.

Vaccinated people were better protected than unvaccinated people, even when Delta took over. In states like Massachusetts, less than 1 percent of fully vaccinated people in the state had tested positive for Covid-19 by the fall of 2021. Other analysis showed that people who weren’t fully vaccinated were nearly five times more likely to get infected, ten times more likely to be hospitalized and eleven times more likely to die from Covid than fully vaccinated people.

But Delta reminded people, or made them understand for the first time, that the vaccines weren’t bullet-proof. New indoor mask mandates were imposed, including at schools, where educators just weeks earlier had been eager for the first normal back-to-school season in two years. No vaccine was yet authorized for children under twelve (both Moderna and Pfizer were studying that population), raising concerns that Delta would spread rapidly among them as they gathered in classrooms.

By the end of the summer, people wondered if the pandemic would ever end. Some started talking about the coronavirus as endemic, not a pandemic.

And a big slice of America was still saying “No thanks” to the vaccine.

Moderna begins early-stage trials of mRNA-based HIV vaccine

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Moderna has begun early-stage clinical trials of an HIV mRNA vaccine, the company announced this week. On Thursday, it administered the first doses of a shot it co-developed with the International AIDS Vaccine Initiative to volunteers at the George Washington University School of Medicine and Health Sciences.

Like the company’s COVID-19 vaccine, the new treatment uses messenger RNA to “trick” the human body into producing proteins that will trigger an immune response. Moderna hopes the shot will induce a specific class of white blood cells known as B-cells, which can then turn into broadly neutralizing antibodies. Those proteins are “widely considered to be the goal of HIV vaccination, and this is the first step in that process,” according to the company.

As part of the trial, Moderna plans to test both a primary vaccine and a booster shot. The Phase 1 trial will involve 56 healthy, HIV-negative adult participants. The company will give 48 of those individuals the mRNA vaccine. Thirty-two of that group will also receive the booster shot. To the final eight involved in the first trial, the company will only administer the booster shot. Moderna says it will then monitor the entire group for six months to gauge the safety of the vaccine. It also plans to examine the immune response the vaccine triggers at the molecular level to determine if it’s effective.

Messenger RNA technology could lead to treatments for a host of deadly diseases, including malaria, but a breakthrough against HIV would be particularly noteworthy. According to statistics from the US government, approximately 1.2 million Americans have the virus, which can lead to the deadly AIDS disease. While outcomes for HIV patients have improved significantly since the ‘90s thanks to the development of new treatments and medication, no HIV vaccine has successfully passed early clinical trials.

Moderna begins early-stage trials of mRNA-based HIV vaccine

Posted on by

Moderna has begun early-stage clinical trials of an HIV mRNA vaccine, the company announced this week. On Thursday, it administered the first doses of a shot it co-developed with the International AIDS Vaccine Initiative to volunteers at the George Washington University School of Medicine and Health Sciences.

Like the company’s COVID-19 vaccine, the new treatment uses messenger RNA to “trick” the human body into producing proteins that will trigger an immune response. Moderna hopes the shot will induce a specific class of white blood cells known as B-cells, which can then turn into broadly neutralizing antibodies. Those proteins are “widely considered to be the goal of HIV vaccination, and this is the first step in that process,” according to the company.

As part of the trial, Moderna plans to test both a primary vaccine and a booster shot. The Phase 1 trial will involve 56 healthy, HIV-negative adult participants. The company will give 48 of those individuals the mRNA vaccine. Thirty-two of that group will also receive the booster shot. To the final eight involved in the first trial, the company will only administer the booster shot. Moderna says it will then monitor the entire group for six months to gauge the safety of the vaccine. It also plans to examine the immune response the vaccine triggers at the molecular level to determine if it’s effective.

Messenger RNA technology could lead to treatments for a host of deadly diseases, including malaria, but a breakthrough against HIV would be particularly noteworthy. According to statistics from the US government, approximately 1.2 million Americans have the virus, which can lead to the deadly AIDS disease. While outcomes for HIV patients have improved significantly since the ‘90s thanks to the development of new treatments and medication, no HIV vaccine has successfully passed early clinical trials.

Moderna enters clinical trials for its mRNA-based flu vaccine

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Moderna has injected its mRNA-derived vaccine for the seasonal flu into a human volunteer for the first time as part of a Phase 1/2 clinical study, the company announced on Wednesday. 

This is a very early test for the new vaccine technology, geared primarily towards building a baseline understanding of the treatment's "safety, reactogenicity and immunogenicity," according to a Moderna release. mRNA-1010, as the vaccine has been dubbed, is designed to be effective against the four most common strains of the virus including, A H1N1, H3N2, influenza B Yamagata and influenza B Victoria. 

According to the World Health Organization, these strains cause between 3 and 5 million severe cases of flu every year, resulting in as many as 650,000 flu-related respiratory deaths annually. In the US alone, roughly 8 percent of the population comes down with the flu every winter. The company hopes this vaccine will prove more potent than the current 40 to 60 percent efficacy rate of conventional flu vaccines.  

“We are pleased to have begun this Phase 1/2 study of mRNA-1010, our first mRNA seasonal flu vaccine candidate to enter the clinic. We expect that our seasonal influenza vaccine candidates will be an important component of our future combination respiratory vaccines,” Moderna CEO Stéphane Bancel said. “Respiratory combination vaccines are an important pillar of our overall mRNA vaccine strategy. We believe that the advantages of mRNA vaccines include the ability to combine different antigens to protect against multiple viruses and the ability to rapidly respond to the evolution of respiratory viruses, such as influenza, SARS-CoV-2 and RSV. Our vision is to develop an mRNA combination vaccine so that people can get one shot each fall for high efficacy protection against the most problematic respiratory viruses."

This vaccine has been generated using the same genomic techniques the company utilized to develop its COVID-19 treatment in 2020. The technique works by exploiting the human body's own cells to reproduce snippets of viral DNA to instigate an immune response and prime the body against future infection. Since this method doesn't require the entire virus (either weakened or dead) but rather just a birt of its genetic code, mRNA vaccines could be applied to any number of deadly modern diseases including malaria, TB — even cancer.  

Flesh-Eating Bacteria Kills 2 Persons in Florida

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There have been eight Vibrio vulnifucus (flesh-eating bacteria) infections in Florida residents. And up until now two have died from the disease as well, according to Florida Department of Health....

Listeria Outbreak Hits California and Maryland

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A multistate outbreak of Listeria has caused one death and seven hospitalizations in California and Maryland. Eight people were infected altogether and one of them died. Two of the affected were...

Listeria Outbreak Causes One Death

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The epidemic was caused by the consumption of spoilt cheese products. All of the people who caught the illness were of Hispanic ancestry. The listeria bacteria cause listeriosis, a disease which has...