Fauci: Vaccine Booster Should Spark Strong Immune Response
Will it stop the rise of COVID-19 delta variant?
Healthcare workers are expected to be a priority for COVID-19 vaccine booster shots this fall, providing more protection against the highly transmissible delta variant and likely reducing breakthrough infections.
“Healthcare workers were among the very first group prioritized to receive the vaccine. If we look at the eight-month interval, which is now being discussed, they would be among the early recipients of the booster,” says William Schaffner, MD, professor of health policy at Vanderbilt University. “Obviously, they are also considered to be at high risk.”
The plan, as this report was filed, was to begin booster doses on Sept. 20 to those who received at least one dose of an mRNA vaccine at least eight months prior, the Department of Health and Human Services (HHS) announced in a joint statement representing its leading medical personnel in all agencies.1
“At that time, the individuals who were fully vaccinated earliest in the vaccination rollout, including many healthcare providers, nursing home residents, and other seniors, will likely be eligible for a booster,” the statement said.
Final approval is contingent on an FDA safety and effectiveness review, and the CDC’s Advisory Committee on Immunization Practices (ACIP) “issuing booster dose recommendations based on a thorough review of the evidence,” HHS stated. “We also anticipate booster shots will likely be needed for people who received the Johnson & Johnson (J&J) vaccine. Administration of the J&J vaccine did not begin in the U.S. until March 2021, and we expect more data on J&J in the next few weeks.”
As medical director of the National Foundation of Infectious Diseases, Schaffner is liaison member of ACIP, which scheduled a meeting for Aug. 30. Booster shots are likely to come up for discussion.
“I wouldn’t be surprised if there is a vote,” Schaffner said. “The President’s Task Force has said sometime in September we will start boosting, and people really need to plan for that.”
Approval would appear to be little more than a formality, particularly since the FDA recently approved full licensure for the Pfizer mRNA shot. (See related story in this issue.) It seems unlikely ACIP would want to get bogged down in booster data for the same vaccine, particularly since the panel recently approved a third shot for the immune-compromised with either mRNA vaccine (Pfizer or Moderna). Adding considerable pressure to the public health response is the delta variant, the most formidable and successful version of SARS-CoV-2 to arise since the pandemic began.
In the meeting slides from an internal discussion, the CDC said the delta variant has an R naught — the number of susceptible people who will be infected by one case — between 5 and 8. The R naught for SARS-CoV-1 in 2002-2003 was thought to be little more than one. The CDC estimates the SARS-CoV-2 delta variant is as transmissible as chickenpox, and more transmissible than Middle East respiratory syndrome, SARS, Ebola, seasonal flu, the 1918 pandemic flu, and the common cold.
Given this threat, the American College of Emergency Physicians (ACEP) is urging booster shots for their members as a top priority. “As emergency beds continue to fill up in hospitals across the country, we cannot afford to lose physicians on the frontlines,” ACEP President Mark Rosenberg, DO, MBA, FACEP, said in a statement.2
New details about the delta variant eluding vaccines makes highly exposed emergency workers vulnerable, Rosenberg stressed.
The American Nurses Association (ANA) also urged its members to get the booster. In a recent survey, 85% of nurses responding said they intended to.3
“We realize the only way we are going to get this delta strain under control is if we all get vaccinated,” says ANA President Ernest Grant, PhD, RN, FAAN. “That is evidence-based science. And now science is pointing to the fact that we need this booster. We will continue to encourage that. We want to protect the nurses, their families, their patients. There are multiple reasons we are in support of the booster, particularly because the delta variant is a huge game-changer.”
Indeed, preliminary data through Aug. 6 from two CDC vaccine effectiveness cohort studies — which included 4,000 vaccinated healthcare personnel, first responders, and other frontline workers in eight national locations — show waning effectiveness against symptomatic and asymptomatic infection with the delta variant, Rochelle Walensky, MD, director of the CDC, said at an Aug. 18 White House briefing.4 In the healthcare workers, vaccine efficacy dropped from 92% before delta to 64% after delta, she added.
The vaccines remain strongly protective against hospitalization and death, but nobody wants to wait until that mortal efficacy starts eroding. “We are concerned this pattern of decline we are seeing will continue in the months ahead, which could lead to reduced protection against severe disease, hospitalization, and death,” U.S. Surgeon General Vivek Murthy, MD, MBA, said at the briefing.
The Big Boost
Rather than simply a third shot that will wane in eight months, the booster should produce a multiplier effect on the immune system, said Anthony Fauci, MD, director of the National Center for Allergy and Infectious Diseases.
“The booster mRNA immunization increases antibody titers by at least tenfold,” Fauci noted at the briefing. “You get a dramatic increase in antibody titers when you do a third immunization dose.”
The booster could imprint longer-lasting immunity, refreshing the memory of B cells and T cells in the immune system while greatly increasing neutralizing antibodies.
“Part of the biology of boosting is that it really gives you a faster antibody response, and one that is higher than the initial series provided,” Schaffner explains. “There are data to support that it will provide long-term protection.”
The booster will be the same mRNA vaccine with which people were inoculated originally. Thus, this booster will not be tailored against the delta variant, but there is ongoing research in that regard, Schaffner says. Still, the real-world effect of the booster remains relatively unknown, though theoretically by increasing antibody titers it could reduce the level of SARS-CoV-2 breakthrough infections.
“We hope with a higher serum antibody level you would get more antibody at the surface of mucous membranes, thus preventing the initial infection, making it less likely that a person who is vaccinated could be a transmitter of the infection,” Schaffner says.
That is what happened this summer in a large SARS-CoV-2 outbreak in Barnstable County, MA.
“During July 2021, 469 cases of COVID-19 associated with multiple summer events and large public gatherings in [Barnstable County] were identified,” the CDC reported.5 “Approximately three-quarters (346; 74%) of cases occurred in fully vaccinated persons.”
The outbreak prompted the CDC to call for a return to indoor masking among the vaccinated and raise a warning that even vaccinated people can transmit SARS-CoV-2 if they are shedding sufficient virus for transmission.
“[On] rare occasions, some vaccinated people infected with the delta variant after vaccination may be contagious and spread the virus to others,” Walensky said at a press conference. “This new science is worrisome and, unfortunately, warrants us to update our recommendations. Vaccinated individuals continue to represent a very small amount of transmission occurring around the country.”
In investigating the Barnstable County outbreak, the CDC found “cycle threshold values” of SARS-CoV-2 viral loads were similar among specimens from patients who were fully vaccinated and from those who were not vaccinated.
“High viral loads suggest an increased risk of transmission and raise concern that, unlike with other variants, vaccinated people infected with delta can transmit the virus,” Walensky said.
A study in preprint revealed delta replicates to viral loads a thousand times higher than the original SARS-CoV-2 strain.6 That could partially explain its shorter incubation period, high transmissibility, and greater ability to cause breakthrough infections in the vaccinated. Another study in Singapore documented breakthrough infections, but encouragingly found less serious infections and saw viral titers drop faster in vaccinated people.7
“The delta variant seems to produce the same high amount of virus in both unvaccinated and fully vaccinated people,” the CDC reported in an update.8 “However, like other variants, the amount of virus produced by delta breakthrough infections in fully vaccinated people also goes down faster than infections in unvaccinated people. This means fully vaccinated people are likely infectious for less time than unvaccinated people.”
COVID-19’s Long Shadow
This viral decline phenomenon has caused some hope and speculation the delta variant might be less likely to cause long COVID than the alpha variant, particularly in those who are vaccinated. We will know soon enough. The alpha variant, which can linger in the body, has heretofore caused most of the long COVID cases, a malingering condition that besets patients with fatigue, brain fog, neurological, and sensory symptoms that can go on for weeks and months. A recently published Israeli study revealed 19% of fully vaccinated healthcare workers experienced long COVID for more than six weeks after breakthrough infections with the alpha variant.9
“Generally speaking, because delta does not last in the body the way alpha strain does — we are thinking, anecdotally, that perhaps long COVID may not be as dramatic in these individuals,” says Sharagim Kemp, DO, a primary care physician and the coordinator of Nuvance Health’s COVID-19 Recovery Program at two facilities in New York and Connecticut. “The preliminary data that 85% of [long COVID ] we are we dealing with is from the alpha variant. The majority of the long-haulers [are alpha]. [With] community infections, the majority are delta. Remember, time is of the essence and this data is emerging. We are not seeing long COVID in delta yet, but remember by definition it has to cause symptoms more than four weeks out.”
However, long COVID in the unvaccinated could be a much different story. Kemp is trying to secure equipment to begin distinguishing between different variants of coronavirus. Vaccination improved symptoms for those who developed long COVID after acquiring the alpha variant — before the delta variant began.
“In the unified data we have seen, individuals who get vaccinated are actually having some resolution of their symptoms,” Kemp says. “Can we explain why? Not with certainty. It could have to do with the immune response in general — maybe a different immune response that overrides what is already occurring. Of the patients I see in New York, approximately 75% have noted some improvement in their symptoms after vaccination. Not complete resolution, but improvement. People who had severe disease, with lung scarring and organ damage — the vaccine isn’t going to do a lot for them.”
More data are forthcoming because it appears the unvaccinated are acquiring delta in the community and then coming to Nuvance facilities with symptoms of long COVID.
“The important thing is that the majority of people who have been long-haulers are in the unvaccinated population,” Kemp says. “That is exactly what we are seeing now — the community population is getting the delta, including children. We are seeing this rise in child cases, which we didn’t necessarily have with the alpha strains.”
Thus, in a maddening nutshell, those who refuse vaccination are at higher risk of exposing family, friends, and co-workers, of hospitalization and death, and possibly long COVID if they survive to discharge.
Although Kemp is hopeful about delta clearing the body quickly, it remains unknown whether it will cause long COVID after breakthrough infections in vaccinated healthcare workers, or allow them to transmit the virus. That said, the vaccine improves the symptoms in many long-haulers. Those vaccinated will certainly be offered the booster shot, Kemp says.
Given the projected power of the booster, Fauci noted it might stop transmission after breakthrough infections.
“Transmissibility is a bit trickier than looking at a clinical phenomenon such as infection, seriousness of disease, and hospitalization,” he said.4 “The increase with a boost is really quite striking — multiple-fold increase — [so] it is conceivable that that would be important in lowering the level of virus in the nasopharynx, which could have an impact on transmission.”
The question of enhanced virulence remains unanswered, but the CDC noted it is “likely more severe.”10 The CDC cited three studies in meeting materials that report indicators of increased virulence, with one from Canada revealing higher odds of hospitalization, ICU admission, and death.11 Researchers in Singapore cited higher odds of oxygen requirements, ICU admission, pneumonia, and death.12 Finally, investigators in Scotland reported higher odds of hospitalization with the delta variant.13
- Department of Health and Human Services. Joint statement from HHS public health and medical experts on COVID-19 booster shots. Aug. 18, 2021.
- American College of Emergency Physicians. ACEP urges FDA to prioritize emergency physicians for COVID-19 booster. Aug. 13, 2021.
- American Nurses Association. New survey data: Nurses recommend COVID-19 vaccines and support mandates and boosters if recommended. Aug 18, 2021.
- The White House. Press briefing by White House COVID-19 Response Team and public health officials. Aug. 18, 2021.
- Brown CM, Vostok J, Johnson H, et al. Outbreak of SARS-CoV-2 infections, including COVID-19 vaccine breakthrough infections, associated with large public gatherings — Barnstable County, Massachusetts, July 2021. MMWR Morb Mortal Wkly Rep 2021;70: 1059-1062.
- Li B, Deng A, Li K, et al. Viral infection and transmission in a large, well-traced outbreak caused by the SARS-CoV-2 delta variant. MedRxiv 2021; July 23. doi: https://doi.org/10.1101/2021.07.07.21260122. [Preprint].
- Chia PY, Ong SW, Chiew CJ, et al. Virological and serological kinetics of SARS-CoV-2 delta variant vaccine-breakthrough infections: A multi-center cohort study. MedRxiv 2021; July 31. doi: https://doi.org/10.1101/2021.07.28.21261295. [Preprint].
- Centers for Disease Control and Prevention. Delta variant: What we know about the science. Updated Aug. 26, 2021.
- Bergwerk M, Gonen T, Lustig Y, et al. Covid-19 breakthrough infections in vaccinated health care workers. N Engl J Med 2021; Jul 28:NEJMoa2109072. doi: 10.1056/NEJMoa2109072. [Online ahead of print].
- McMorrow M. Improving communications around vaccine breakthrough and vaccine effectiveness. July 29, 2021.
- Fisman DN, Tuite AR. Progressive increase in virulence of novel SARS-CoV-2 variants in Ontario, Canada. MedRxiv 2021; Aug. 4. doi: https://doi.org/10.1101/2021.07.05.21260050. [Preprint].
- Ong SWX, Chiew CJ, Ang LW, et al. Clinical and virological features of SARS-CoV-2 variants of concern: A retrospective cohort study comparing B.1.1.7 (Alpha), B.1.315 (Beta), and B.1.617.2 (Delta). SSRN 2021; June 7. doi: 10.2139/ssrn.3861566. [Preprint].
- Sheikh A, McMenamin J, Taylor B, et al. SARS-CoV-2 delta VOC in Scotland: Demographics, risk of hospital admission, and vaccine effectiveness. Lancet 2021;397: 2461-2462.
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