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Developing a SARS-CoV-2 vaccine and getting it to everyone in the United States who needs it will be difficult, but lessons learned from the 2009 H1N1 influenza pandemic can help, the Advisory Committee on Immunization Practices (ACIP) said at a June 24 meeting.
“We recognize that we’re asking ACIP to do an insurmountable task in the absence of sufficient data, and yet this is the situation that we at CDC find ourselves in,” Nancy Messonnier, MD, director of the Center for the National Center for Immunization and Respiratory Diseases (NCIRD), Centers for Disease Control and Prevention (CDC), said during the meeting.
“As always when we’re faced with tasks that seem insurmountable, we come to ACIP to get your advice. [W]e know that you don’t have perfect information, and yet we’ve never needed your guidance more than we do right now,” she continued.
Vaccine Catch-up Vital Ahead of Influenza Season, COVID-19 “Second Wave”
Experts at the meeting said that it’s crucial that patients who have delayed receiving vaccines catch up as quickly as possible.
Childhood vaccination rates are still “well below baseline,” despite beginning to rebound in May, Melinda Wharton, MD, MPH, director, Immunization Services Division, NCIRD, CDC, said in a presentation to the committee.
The Vaccines for Children program has an important role to play at a time when many parents may be without insurance or the ability to pay for vaccines, Wharton continued. She encouraged clinicians to inform patients and their caretakers about the program.
“It’s really critical that we address catch-up now, to allow us to move on to back-to-school vaccination in the summer and influenza vaccination in the fall,” Wharton explained.
“In the event that COVID-19 circulation disrupts those back-to-school vaccination efforts, we’d encourage jurisdictions if possible to allow additional time for compliance rather than suspending school requirements completely through some sort of emergency action or creating a situation where families feel like they need to seek exemptions,” she continued.
“Because we expect that SARS-CoV-2 will continue to circulate into the fall, influenza vaccination will be an important strategy to decrease stress on our healthcare system by decreasing doctor visits and hospitalizations as well as decreasing the number of people who will need diagnostic testing,” Wharton added.
Identify Priority Groups for SARS-CoV-2 Vaccination
After a SARS-CoV-2 vaccine has been developed, the goal is to have enough for the entire US population, but this may not be possible. So it’s essential to identify certain priority groups early when planning vaccination programs, Sarah Mbaeyi, MD, MPH, CDC/NIRD, said during the meeting.
Vaccine prioritization is complicated by the lack of complete information about epidemiology and vaccines for COVID-19, including characteristics, timing of vaccines, and number of doses needed.
Mbaeyi said there are several lessons to be learned from the 2009 H1N1 influenza pandemic. The disease emerged during April 2009 and progressed to a global pandemic. A vaccine became available during the second influenza wave that October. At that time, ACIP recommended prioritizing for initial vaccination those at increased risk for severe illness and healthcare personnel.
In 2018, the CDC realized it needed a plan for prioritizing vaccines to respond to vaccine supply shortages and to manage program planning. The agency updated its guidance for allocating and targeting pandemic influenza vaccine on the basis of those lessons learned.
Vaccine supply projections had been “overly optimistic.” Vaccine surpluses occurred as a result of “restrictive enforcement of priority groups,” and expanding vaccination beyond priority groups to the general public was challenging. Population values were important, and national guidance as well as flexibility in implementation at the state and local levels were needed, Mbaeyi said.
To facilitate prioritization, the CDC grouped occupational and high-risk populations into five tiers for pandemic influenza vaccination. The highest-risk group, tier 1, includes occupational groups such as deployed personnel; public health personnel; critical healthcare workers; pharmacists and pharmacy technicians; emergency medical services, law enforcement, and fire services; and pandemic vaccine and antiviral drug manufacturers. High-risk populations in tier 1 include pregnant women and infants and toddlers.
Proposed additions to this group for SARS-CoV-2 vaccination include adults aged 65 years and older, residents of long-term care facilities, and those with high-risk medical conditions. The highest tier, for the general population, is tier 5.
“This last came out in 2018… The initial process to develop this took multiple years and involved lots of stakeholder and public outreach,” Messonnier said. The CDC has built on the pandemic influenza framework for SARS-CoV-2 vaccination, “knowing that unfortunately we don’t have 2 years to figure this out.”
If they later determine that four tiers is more appropriate, the framework can be changed, she said, adding, “When more data become available on the different vaccines, the tiers will be adjusted. If the first vaccine available is less immunogenic in older adults, then that would change your tiering.”
This framework could be useful for planning the vaccination approach for SARS-CoV-2, Mbaeyi noted, although she agreed that prioritization will need to be refined on a continual basis as additional epidemiology and immunology data become available. She cautioned that although there are concerns about possible reduction in efficacy in some populations, such as older adults and immunocompromised persons, these groups should not be excluded as priority groups while waiting for additional data to become available.
“Subprioritization” may be needed if there is an insufficient number of initial doses to vaccinate all persons in priority groups or it becomes necessary for program planning purposes.
High-Risk Groups, Not Individuals, Are Key Target
“Our plans to operationalize this are…to target not individuals but to target groups, so, for example, the essential workers and others in these tier 1 groups,” Messonnier said.
Possible ways of reaching these groups include taking vaccination to hospitals or poultry plants where people work while leaving room for those not in higher-risk groups to make decisions for themselves, she added. “We think that [federally qualified health centers are] a key group that we’re working with now around influenza vaccination.”
Similarly, if ACIP recommends prioritizing minority groups, which have been severely affected by COVID-19, vaccination efforts might include beauty salons or other places where individuals congregate.
“Part of the reason we want this discussion early about how…[ACIP recommends] we prioritize is that then we want to turn it into operational planning with state and local health departments.… We’ve learned from H1N1 we don’t want to overengineer it, but until you articulate to us how we should prioritize, we can’t get to the next step,” Messonnier explained.
Multiple Potential Vaccines in Clinical Trials
A number of potential vaccines against SARS-CoV-2 are currently being explored.
The potential vaccines use various platforms, including RNA (LNP-mRNA, Moderna/NIAD, phase 2; and 3 LNP-mRNA vaccines, Pfizer/BioNTech, phase 1/2), nonreplicating viral vector (chimpanzee adenovirus, University of Oxford/AstraZeneca, phase 1/2; and adenovirus type 5, CanSino Biol, phase 2), DNA (DNA plasmid electroporation, Inovio Pharm, phase 2), inactivated (inactivated ±alum, multiple Chinese developers, phase 1/2), and protein subunit (recombinant GP nanoparticle/matrix M, Inovio Pharm, phase 1).
Vaccines have been explored for other coronaviruses, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and lessons from those studies can be useful when developing a vaccine for SARS-CoV-2, Kathleen Neuzil, MD, MPH, professor of medicine and pediatrics and director, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, said in a presentation to the committee.
“We know both of those prior coronaviruses have good vaccine responses to several constructs in animals. There were vaccines that made it to baseline human trials for both SARS and MERS; they showed broadly neutralizing antibodies. The MERS vaccine development continues, and unfortunately, SARS investments were reallocated, so we did not get very far with SARS vaccine development,” she explained.
The spike glycoprotein on the coronavirus plays an important role in the ability of the virus to enter and infect cells in the body, and it is a main target of vaccine research, Neuzil said.
“In the context of vaccine development, you will hear a lot about the type of spike protein that’s used — if it’s the full-length protein, if it’s the receptor binding domain, if it’s the prefusion or postfusion form,” she said. “This protein is a metastable protein; it undergoes this major structural rearrangement to be able to fuse the viral membrane with the host cell membrane, so we are trying with vaccines to get antibodies to disrupt that binding.”
Neuzil added, “What we don’t know that would be helpful to vaccine development is the level of antibody needed to prevent reinfection. We don’t know the duration of protection from natural immunity, and we don’t yet know how important T-cell immunity is to either prevent infection or reinfection.”
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