A summary of presentations from the weekly Summit partner webinars
September 14, 2023 – The latest Summit Summary
ACIP Update – Melinda Wharton (CDC)
Melinda Wharton, MD, MPH, Associate Director for Vaccine Policy, NCIRD, CDC, gave an overview on the September 12, 2023 ACIP meeting on COVID-19 recommendations.
Background COVID-19 vaccine 2023–2024 season
- January 26: VRBPAC supported updated monovalent COVID-19 strain for 2023–24 season
- February 24: CDC discussed a simplified schedule like the flu schedule where younger previously unvaccinated children are recommended to get a primary series and everyone else gets one dose of the updated vaccine
- Committee was supportive
- Many decisions weren’t discussed in full detail such as.
- Extra doses for immunocompromised people
- How changes would be incorporated into the childhood schedule
- No vote was taken
- April 18: FDA amended the EUA for Pfizer and Moderna mRNA bivalent vaccines to align with a simplified schedule
- April 19: ACIP discussed changes and implementation; gaps were identified
- June 15: VRBPAC discussed strain selection and committee support of XBB lineage for 2023–24 COVID-19 vaccine
- June 16: FDA announced selection of XBB.1.5 lineage for vaccine
- September 11: FDA approved and authorized XBB lineage monovalent mRNA vaccines for 2023–24 season
Proposed Data Package Needed from Manufacturers for Authorization/Licensure
- Vaccine manufacturers would prepare a preclinical data package to support effectiveness of updated vaccine to VRBPAC
- Data to include
- Chemistry, manufacturing, and control data to ensure quality and consistency
- Pre-clinical data to support effectiveness
- Data prior to authorization or approval based on criteria
- Experience of manufacturer
- Genetic and antigenic relatedness
- Prior demonstration of efficacy
- Clinical data needed post-authorization or approval for ongoing evaluation of vaccine composition
FDA Regulatory Actions (September 11)
- FDA approved updated monovalent mRNA vaccines for use in people age 12 years and older and EUA for use in age 6 months–11 years
ACIP meeting (September 12)
- ACIP signed off on FDA’s recommendation for monovalent vaccine with XBB.1.5 lineage
- Did not make recommendations for Novavax
- Vote on recommendation for updated vaccines
Could incorporate additional updated vaccines like Novavax after authorized by FDA in the coming weeks or months
Current Landscape of SARS-Co-V-2 Lineages
- More than 90% of what’s circulating continues to be XBB lineage
- Evolved from XBB.1.5, but they are closely related
- Discussion addressed concerns about the BA.2.86 lineage that has more than 30 amino acid substitutions
- Low number of changes detected so far in the binding pocket so less likely to impact effectiveness
Hospitalization Data
- COVID-19-Associated Hospitalizations in People with Underlying Medical Conditions – Pediatric (January–June 2023)
- 75% of hospitalized pediatric patients younger than 6 months had no underlying medical conditions
- Proportion of older children without high-risk conditions is smaller
- Lower for older age groups where most adults have underlying conditions
- Hospitalization rates for children were higher for COVID-19 compared to influenza in 2021–22 but were comparable in 2022-23.
- Cumulative Weekly Rates of COVID-19- and flu-Associated Hospitalizations – Adults Age ≥18 (October 2022–July 2023)
- For adult age groups, hospitalizations were higher for COVID-19 than for flu
- COVID-19-Associated Hospitalizations in People with Underlying Medical Conditions – Adults Age ≥18 (January–June 2023)
- Vast majority of adults had underlying conditions, including 58% of those 18-49 years, 72% of those 50-64, and 81% of those 65+ years having 3 or more conditions
- Summary COVID-19-associated hospitalizations
- Hospitalization rates have increased in all age groups since mid-July
- Rates highest in older adults and in infants under age 6-months
- Most children under age 5 hospitalized with COVID-19 had no underlying medical conditions
- Proportion higher in older children
- Most hospitalized adults have multiple underlying health and medical conditions
- COVID-19 continues to cause severe illness
- Clinical outcomes generally comparable to flu-associated hospitalizations
- Most children and adults hospitalized for COVID-19 since January 2023 have not received updated bivalent booster
Post-COVID-19 Conditions
- Common following SARS-CoV-2 infection and decrease with time
- Decreased prevalence since start of pandemic
- Symptoms and conditions associated are not unique to having had prior SARS-CoV-2 infection
- Associated with increased healthcare utilization and significant activity limitations
- Accumulating evidence suggests vaccination reduces post-COVID-19 conditions in all ages
Vaccine Effectiveness (VE)
- Infection-induced immunity high in all age groups
- Benefit of COVID-19 vaccination in a population with high infection-induced immunity remain
- Updates to waning bivalent vaccine effectiveness
- VE waning identified against hospitalization and emergency department/urgent care visits
- More sustained protection against critical illness
- Low uptake of bivalent doses in younger age groups prevented assessment of waning beyond 4 months from bivalent dose
- People with immunocompromise may have reduced protection after vaccination compared to people without immunocompromise
- Historically COVID-19 VE has been lower and waned more quickly in immunocompromised adults
- VE findings should be interpreted as incremental benefits provided by vaccine in population with high prevalence of infection-induced immunity
Moderna – Safety and Immunogenicity of COVID-19 Vaccine (2023–2024) XBB.1.5 Vaccine
- Safety profile of XBB.1.5 vaccine
- Small study in adults
- Consistent with previously authorized vaccine
- Generated robust neutralizing antibody titers against recent evolved variants including BA.2.86
- Anticipate will be effective against currently circulating variants
- Cross neutralization results
- Small number of participants who received updated vaccine, with prior or no prior infection
- Had good responses to new strains tested
- Homologues strain to XBB.1.5 had 13-fold increase in people with no prior infection and 7.9-fold increase in people with prior infection
- For BA.2.86 had 14-fold increase in people with no prior infection and 5.4 increase in people with prior infection
- Titers higher in people with prior infections
Novavax – Neutralizing Responses in Macaques: Primary Vaccination Bivalent BA.5 Vaccine and Boost with XBB.1.5
- Study in macaques to look at booster dose of updated vaccine in animals that have previously received their bivalent primary series
- Good booster response
- Neutralizing antibodies against the newer strains
- No data on BA.2.86 strain
- Similar to the mRNA vaccines
Pfizer – Monovalent Booster VE Neutralized Predominant and Emerging Variants
- Study in mice comparing additional dose of updated vaccines in animals that have previously received the bivalent vaccine
- Compared to animals that just got another dose of the bivalent vaccine
- New vaccine provided better antibody response to the new viruses than when getting another dose of bivalent vaccine
Pediatric Vaccine-Preventable Diseases: Deaths Per Year in the U.S. prior to Recommended Vaccines Compared to COVID-19
- Comparing mortality in other vaccine-preventable diseases with COVID-19-related deaths in children
- Among kids, many more deaths with COVID-19 than with other vaccine-preventable diseases (VPD)
- Substantial burden of mortality among children relative to other VPDs
Summary: Public Health Problem (from COVID-19 workgroup)
- COVID-19 burden currently lower than previously, but still a high absolute number of hospitalizations and deaths.
- Hospitalization rates are currently low; some age groups have increased in recent weeks/months
- Expect further increases due to respiratory disease season from multiple viruses
- Infants and older adults have highest COVID-19 hospitalization rates
- Children and adults with no underlying medical conditions still experience severe illness due to COVID-19 and post-COVID-19 conditions
- Common
- Decrease with time since infection
- Have decreased since start of pandemic
- People in racial and ethnic minority groups continue to be disproportionately impacted
- High proportions of underlying conditions may put certain groups of increased risk for severe outcomes due to COVID-19
Summary: Benefits and Harms
- Monovalent XBB vaccine increase the immune response against currently circulating variants
- Last year’s updated bivalent vaccine was effective at preventing medically attended COVID-19 hospitalizations and death due to COVID-19
- Vaccination reduces the risk of post-COVID-19 conditions among both children and adults
- Vaccines have a high degree of safety
- Cases of myocarditis and anaphylaxis seen in post-authorization studies
- Unlikely that the formulation change would increase those
- Benefits anticipated in all age groups for which risk of myocarditis is highest
- Vary by age and incidence of COVID-19 hospitalization
- Benefits outweigh the risks in the age groups in which myocarditis is highest
- Modeling done which projects many more hospitalizations and deaths averted when updated dose is universally recommended compared to no recommendation or recommended only for persons age + 65 years
Summary: Values
- Recent data about attitudes and values
- Most people feel like things are getting better
- Some people moderately concerned about having family members become seriously ill from COVID-19
- People in racial and ethnic minority groups, those living in urban areas, and those with lower incomes who have been hit hard by pandemic are more concerned about getting COVID-19 illness than other groups
Summary: Acceptability
- Vaccine receipt is not uniform across populations and age groups
- People age 65+ continue to have the highest intent to receive vaccine
- Confidence in vaccine safety differs across the population
- Compared to other vaccines, COVID-19 vaccines were recommended the least by healthcare providers
- When a provider recommends it, people far more likely to get vaccinated
- Encouraging healthcare providers to recommend and administer could help increase confidence
Summary: Feasibility
- Lower minimum dose order sizes for providers compared to larger orders required early in the COVID-19 vaccine response
- Single unit packaging
- Easier storage
- Reduce waste
- Lower chance of errors
- Three seasonal vaccines for respiratory diseases (flu, COVID-19, and RSV vaccine (for 60+) plus RSV monoclonal antibody (for infants))
- More vaccines to manage and store
- More challenges around administration errors
- COVID-19 vaccines will continue to be accessible after commercialization
- Readily available resources for those who are uninsured or underinsured or who reside in underserved communities through Bridges Program
Summary: Cost-effectiveness Model
- For adults age 18+, COVID-19 vaccination is a cost-effective intervention
- In those age 50-64 years, cost-effectiveness was robust and cost-saving for adults 65 years and older
- For younger people (age 18–49), cost-effectiveness depends on a lot on the inputs such as disease burden
- Cost-effectiveness estimates are not yet available for the pediatric population
Summary and Workgroup Interpretation: Considerations Regarding a Universal vs Non-universal Policy
- Should there be universal recommendations for everyone?
- Workgroup requested additional data on severe illness due to COVID-19 in those with and without underlying conditions
- All groups had risk of severe illness
- Vast majority of U.S. population has underlying condition (risk-based recommendation)
- Would not allow COVID-19 vaccines to everyone who wanted them based on shared clinical decision-making
- Non-universal recommendations would need to be quickly revisited if increase in burden
- COVID-19 disease burden may increase over time
- COVID-19 recommendations should be reviewed on an ongoing basis
Summary and Work Group Interpretation: COVID-19 Vaccine Recommendations for Children
- Burden of illness is lowest in age 5–17 years
- Still hundreds of deaths due to covid between 2021–22
- Half of pediatric COVID-19 deaths were in individuals with no underlying conditions
- Number of COVID-19 hospitalizations and deaths are comparable to the burden seen with other vaccine-preventable diseases for which there are universal recommendations, including influenza
- Potential additional benefits for vaccinations
- Prevention of post-COVID-19 conditions
- Reduced school absenteeism
- Risk of myocarditis
- Lower than the risk seen following the primary series
- Might be due to the longer interval between doses than there was with primary series
- At this point the work group was supportive of universal recommendation
Proposed ACIP Voting Language
- ACIP recommends 2023–24 monovalent, XBB-containing, COVID-19 vaccines as authorized under EUA or approved by BLA in persons age ≥6 months
- Once Novavax is authorized, it will most likely fall under this recommendation,
- Recommendation was approved by AAP, and accepted and adopted by CDC Director
Proposed 2023–24 mRNA COVID-19 Vaccine Recommendations
- Everyone age 5+ gets one dose of new mRNA vaccine
- Children age 6-months–4 years need complete multi-dose initial series (2 doses of Moderna or 3 doses of Pfizer) with at least one dose of 2023–2024 vaccine
- People moderately or severely immunocompromised need to complete a three dose initial series and at least one dose of updated vaccine
- May receive one or more additional dose of updated vaccine
Key Changes from Bivalent mRNA Recommendations
- Everyone age 5+ gets single updated vaccine dose
- Not currently a recommendation for additional dose for people age 65+
Commercialization of COVID-19 Vaccines
- Transition from federal procurement to more traditional public/private model
- Ends CDC provider agreement
- Change some of the data collection
- Still have evidence-based vaccination program that develops recommendations to monitor safety and effectiveness
- Works to strengthen vaccine confidence
- CDC working to ensure continuing access to COVID-19 vaccines at no cost to people who don’t have insurance or underinsured
Bridge Access Program
- A temporary “bridge” to a permanent Vaccines for Adults (VFA) program
Questions
Q: Can you address what providers should do if children under age 4 who received an initial dose from a manufacturer’s product that they are not carrying in the commercial market. How should they proceed with those patients to complete the 2- or 3-dose recommendation?
Melinda Wharton (CDC): My understanding is these vaccines are not authorized for mixed sequences. Someone will have to get back to you on that question. Followup from MW: The Interim clinical guidance will be addressing this issue.
Q: Will there be a VIS for adult COVID-19 vaccines?
Melinda Wharton (CDC): I believe there will be, but I’m not sure about timing.
Followup from MW: A VIS is under discussion.
Q: With children, the pediatric COVID-19 vaccine products are still authorized and not licensed, but able to be commercialized prior to licensure. Are there any specific issues for providers to be aware of regarding distribution of authorized vs licensed products?
Melinda Wharton (CDC): The pediatric vaccine is available for ordering by private pediatricians and clinics for their private patients. CDC will be making it available through the vaccines for children program as well. There should be lots of vaccines for public health responses.
Q: Can you clarify the CDC recommendation about coadministration of COVID-19 vaccine?
Melinda Wharton (CDC): Our general approach to coadministration is that it’s allowed, so the COVID-19 vaccine can be coadministered with other vaccines. You can do that probably for most people. There’s a limit to how many vaccines adults may be willing to get at once but if someone really wants to get everything all at once and you don’t say you can’t do it. It’s maybe not a great idea because you probably will have a very sore arm and so forth but coadministration is allowed and that is acknowledging that coadministration of COVID-19 vaccine and flu vaccine with newer vaccines like RSV. There is limited information and I think we have to acknowledge that there does appear to be some lower titers with coadministration for flu vaccine but it’s not clear if there’s any clinical significance. If people feel like coadministration is the right thing to do because patients will only come one time and they’re not going to come back for additional vaccines, that’s fine to give at the same visit.
Q: Thank you for highlighting in your talk the short timeframe from when VRBPAC announced the strain to use for the vaccine and the vaccine being available (June to September). Has VRBPAC talked about moving the strain selection earlier than June for future COVID-19 vaccines? Since the Novavax product (non-mRNA) is manufactured using a different manufacturing platform, does that pose a bigger challenge in the compressed timeframe?
Melinda Wharton (CDC): We are still learning how this rolls out and I’ve not heard discussion about moving strain selection earlier but of course FDA may be considering that. The strain that was selected in June is pretty much gone and the further one moves it back in order to allow addition manufacturing and clinical trials to be done, the further away the vaccine that originally emerges is going to be from what circulating. I think that’s the balance. I know at that June VRBPAC meeting all of the manufacturers asked about their ability to provide vaccines this fall. There possibly are differences in what’s feasible for different technologies but I think that Novavax had said that their product has been submitted to FDA and hopefully it will be across the finish line soon.
Announcements
- The summit held a workshop on August 2, 2023, in Washington D.C. There were three teams that emerged from the workshop who led the work to deliver three resources.
- The meeting report (13 pages) and truncated executive summary is available on the NAIIS landing page: izsummitpartners.org/2023-naiis-august-2
- One deliverable is already available on the landing page: Fall 2023 Respiratory Season Vaccination Decision Making for People 60 and Over. This resource includes a specific algorithm table for how to co-administer RSV, COVID-19, influenza, and pneumococcal vaccination for this upcoming respiratory viral pathogen season.
- The second deliverable, comprising key points to discuss the recommended fall respiratory vaccines, should be approved soon.
- The third deliverable, which is a personalized vaccination action plan, is scheduled to be available soon.
- If you are registered for the Summit not getting the emails from Mailchimp, please add “NAIIS” at info@izsummitpartners.org to your contact list.
- If you have any agenda items that you are interested in sharing with the Summit, please let us know and we can add you to an upcoming call as a speaker or panelist. Contact information: info@izsummitpartners.org.
