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A summary of presentations from the weekly Summit partner webinars

October 5, 2023 – The latest Summit Summary

Flu/COVID/RSV Dashboards Update – Katie Tastad (CDC)

Katie Tastad, MPH, Influenza Division, Domestic Surveillance Team, CDC, gave the last update for the 2022–2023 season, as well as gave an update on the influenza, RSV, and COVID-19 dashboards. New virus data for the 2023–2024 season will be published later this week.

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Respiratory Virus Laboratory Emergency Department (ED) Network Surveillance (RESP-LENS) – This interactive dashboard tracks emergency department visits for laboratory-confirmed severe acute respiratory coronavirus type 2 (SARS-CoV-2), influenza (flu), and respiratory syncytial virus (RSV) illnesses among people presenting to a participating ED’s with acute respiratory illnesses.

  • COVID-19 increased later in the summer, but it appears to have plateaued and is starting to decline on a national level
  • Both influenza and RSV remain low
  • For emergency department visits for age 0–1 years and age 2–4 years, RSV is increasing slightly in some parts of the country

Respiratory Virus Hospitalization Surveillance Network (RESP-NET) ­– This site comprises three platforms that conduct population-based surveillance for laboratory-confirmed hospitalizations associated with COVID-19, Influenza, and Respiratory Syncytial Virus (RSV) among children and adults in the U.S.

  • COVID-19 increased during the summer but appears to be plateauing or possibly starting to decline
  • Flu and RSV are remaining low, with a slight increase in RSV
  • Region 4, southeast states – moderately steep decrease in COVID-19 and a noticeable increase in RSV
  • Region 8, mountain states – no decline in COVID-19 and no noticeable increase in RSV
  • Nationally flu is low

National Emergency Department Visits for COVID-19, Influenza, and Respiratory Syncytial Virus – This site provides a combined view of emergency department visit data for multiple respiratory conditions as tracked by the National Syndromic Surveillance Program (NSSP).

  • No surveillance through FluServ Net during summer months. Stops around end of April and resumes in October for week 40.
  • Seeing same trends for COVID-19 and RSV as for emergency department visits
    • COVID-19 looks to be plateauing and hopefully on the decline
    • RSV activity is low
  • Georgia in region 4
    • Notable decreases in COVID-19
    • Increase in RSV

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Update on RSV Prevention – Kathryn Edwards (Professor of Pediatrics Emeritas Vanderbilt University)

Katheryn Edwards, MD, Professor of Pediatrics Emeritas Vanderbilt University gave an update on RSV vaccines for adults.

Disclosures: grant recipient, CDC (Vaccines Safety with COVID-19 Vaccines, grant recipient, NIH (Mentoring Young Investigators in Vaccine Sciences), consultant at BioNet and Dynavax (pertussis vaccines), consultant at IBM (vaccine safety networks), and consultant for Data Safety and Monitoring Boards at: Sanofi, X-4 Pharma, Seqirus, Moderna, Pfizer, Merck, and Roche

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RSV Structure

  • Body makes antibody to outer envelope of the virus
    • Outer envelope makes protein called F protein (fusion protein)
    • All of vaccines are directed toward F protein
    • Antibody to F protein will prevent virus from adhering to respiratory cell, which prevents infection
  • Two subtypes of RSV: A and B
    • Cocirculate
    • Immunity to one of subtypes confers immunity to the other

Fusion (F) protein exists in two or more structural forms, exposes different antigenic regions

  • Structure of virus changes before virus adheres to the cell
    • Before attaches to cell has prefusion structure
    • Once attaches to the cell it has a postfusion structure
  • For many years, making vaccines to postfusion structure because didn’t know about prefusion structure
    • Postfusion structure antibodies didn’t provide protection
      • Babies with antibodies to postfusion structure had reactions to the vaccine that could make them more ill
    • Knowing about prefusion structure critical to making vaccines
      • Critical to understanding how to make COVID-19 vaccines as well

RSV and influenza burden, compared

  • Impact of flu on adults age 65 and older is more than that of RSV on adults age 65 and older, but RSV still a very important cause in terms of the number of medical encounters, the number of hospitalizations, and number of deaths each year in the United states

RSV-associated hospitalization rates by adult age group, RSV-NET 2016–2020

  • RSV targets certain age groups: older people and babies
  • Hospitalization rates associated with confirmed RSV studied before pandemic
    • Progressive increase in hospitalization rates over past from 2016–2020
    • Each decade rates of hospitalization go up
    • By age 80 years, hospitalization rates are very high
    • About 3.5% of adults age ≥80 years are hospitalized with RSV each year

Underlying medical conditions among adults age ≥18 years hospitalized for RSV: RSV-NET 2014–2018

  • In age 18 years and older who are hospitalized with RSV, almost all have coexisting medical conditions
  • Cardiovascular disease, chronic lung disease, and diabetes are the three leading medical conditions that predisposed to RSV hospitalizations
  • Renal disease, immunocompromising conditions, neurologic disease, chronic metabolic disease, liver, blood, and other conditions also contribute to the comorbidities that lead to hospitalization of patients with RSV
  • Almost 100% of those hospitalizations have underlying comorbid conditions
  • About 50% have 1–2 or greater than 3 comorbid conditions

Outcomes among adults ≥18 years hospitalized for RSV; RSV-NET 2017–2018 to 2019–20 seasons

  • Outcomes in adults that are hospitalized for RSV during the two seasons were significant
  • Almost 20% of those adults who are hospitalized for RSV were admitted to ICU
  • Adults that were admitted to the hospital with RSV had fatality rate of 5%, increasing with increasing age

GSK’s RSV older adult vaccine

  • Contains the RSV prefusion F protein at 120 micrograms (RSVPreF3) and an adjuvant (ASO1E)
  • Given as a single injection
  • Vaccine boosts both antibody and T-cells
  • Antibodies generated: RSV-A Nab and RSV-B Nab
    • Neutralizing titers by the vaccine
    • Even oldest people are generating high titers that persist above baseline for over a year
    • Immunized individuals age 60–80+ years make prefusion F-primed CD4 T-cells
  • Vaccine is capable of inducing neutralizing antibody to both A and B and generating T-cells

GSK pivotal phase 3 trial

  • Pivotal study required for the vaccine to be licensed by the FDA
  • Phase three study that included people age ≥60 years, throughout the world (32% from U.S., 92% form northern hemisphere)
    • 8% age ≥80 years
    • 5% frail with slow gait speed
    • About 1% long term care facility residents
  • 12,000 participants who receive the vaccine and about 12,000 participants who received the placebo
  • Carefully studied for the prevention of RSV
  • Data summarized in MMWR
    • Prevention of RSV-associated lower respiratory tract disease or pneumonia was 82% in season one
      • Season two with no vaccine retained 56% of protection
      • Combining season one and two protection is 75% protection
    • RSV-associated medically attended lower respiratory tract disease was 87% in season one
      • Combining season one and two protection is 77% protection
    • Note that pandemic made burden of RSV less than usual
    • More hospitalizations in the group that received placebo than the then the group that received vaccine
      • Numbers not great enough to be significantly different
    • Safety of the vaccine
      • Serious adverse events include events like hospitalizations, severe reactogenicity events, inflammatory neurologic events
        • Numbers too small to determine relative risk of adverse events
      • 550 in each group (placebo and vaccine) and the relative risk was not greater with the prefusion vaccine
      • Several more severe reactogenicity events in vaccine patients – local swelling or malaise

Bivalent RSV prefusion F vaccine by Pfizer

  • Bivalent, contains 60 micrograms of prefusion A and 60 micrograms of prefusion B
  • Neutralizing titers to A and B at 1, 6, and 12 months after vaccination
    • Neutralization titers in the vaccine group exceed placebo recipients
    • Titers persist at least 12 months
  • Pivotal phase two trial
    • Conducted in age 60 years and older (60% from U.S. and a 76% from the northern hemisphere)
    • About 17,000 in the vaccine group and 17,000 the placebo group
  • Data summarized in MMWR
    • Prevention of RSV-associated lower respiratory tract disease or pneumonia was 89% in season one
      • Season two with no vaccine retained 79% of protection
      • Combining season one and two protection is 84% protection
    • RSV-associated medically attended lower respiratory tract disease was 85% in season one
      • Combining season one and two protection is 81% protection
    • Efficacy similar in both vaccines
    • Numbers too small to determine relative risk of adverse events

Cases of Guillain Barré syndrome (GBS) were reported after vaccination with both investigational vaccines

  • Population-based rates of GBS increase with age
  • RSV infection also associated with GBS but no causal link established between RSV disease and RSV vaccine
  • Continues to be looked at very carefully with the CDC vaccine surveillance network
  • Increase over time with rates of GBS
    • Age ≥65 years are about four times greater than younger individuals for GBS
    • Four times greater for females and seven times greater in males

Deliberations of the ACIP  

Work Group interpretation

  • GSK and Pfizer vaccine both demonstrated significant efficacy against lower respiratory tract disease caused by RSV among people age ≥60 years
    • Trials underpowered to assess efficacy against RSV hospitalization due to pandemic and overall lower rates of RSV than usual
    • Caution that the groups at the highest risk for RSV disease (e.g., people 80 years and older, frail people) were really underrepresented in the clinical trials
  • At least one case of inflammatory neuropathy was observed among recipients of each vaccine
  • Post-licensure surveillance for safety and efficacy critical
    • Very elderly, most frail and those individuals who lived in in chronic care facilities are among those at higher risk of severe illness from RSV

ACIP Recommendations

  • June 21, 2023, the ACIP recommended that adults age ≥60 years could receive a single dose of RSV vaccine using shared clinical decision making
    • Healthcare professionals need to discuss the RSV vaccine with the recipients
    • Recipients need to understand vaccine, RSV disease, safety, and risk factors
    • Helpful data
      • Of patients with chronic underlying diseases that were hospitalized in ICU with RSV, 5% died
      • Patients age ≥60 years with chronic disease should be targeted
        • Lung disease, particularly chronic obstructive pulmonary disease (COPD) and asthma
        • Cardiovascular disease, such as coronary artery disease or congestive heart failure
        • Moderate or severe immunocompromise
        • Diabetes
        • Neurologic conditions
        • Kidney disorders
        • Liver disorders
        • Hematologic disorders
        • Other underlying factors
      • If hospitalized with RSV, 20% go to ICU

Both nirsevimab and maternal RSV vaccine provide passive immunity

  • RSV vaccine given to pregnant mothers for passive immunity transfer to baby through placenta and breast milk
  • Nirsevimab prevents disease in babies and is given to infants <8 months and some higher risk children 9-18 months
    • Not a vaccine
    • Monoclonal antibody for passive immunity
    • Antibodies last six months
    • Studies show to be highly effective for medically-attended lower respiratory tract disease
    • Effective against RSV-related hospitalization
    • Monoclonal antibody 77% to 86% effective against RSV lower respiratory tract illness and related hospitalizations and very severe RSV illness
  • Nirsevimab can prevent severe disease among infants and children age younger than 20 months
    • Recommendation in July of 2023
    • All children <8 months
    • Children 9-19 months at higher risk

RSV maternal vaccination data

  • Vaccine efficacy for severe disease is 70–80% for maternal vaccination
  • Efficacy for RSV-positive lower tract disease is 50–60%

Final vote language

  • September 22, 2023, ACIP recommended RSV vaccination of pregnant people during 32–36 weeks’ gestation using seasonal administration, to prevent RSV lower respiratory tract in infants
  • Voted to approve Pfizer’s bivalent RSVpreF vaccine for the Vaccines for Children (VFC) program (applying to pregnant people under age 19 years)

Options for preventing RSV in Infants from CDC website www.cdc.gov/rsv/about/prevention.html.

The two options to protect your baby are:

  1. Getting an RSV vaccine if you are 32-36 weeks pregnant during RSV season. This vaccine is recommended during September through January for most of the United States because RSV is typically a fall and winter virus. The seasonality of RSV season may vary depending on where you live, and state, local, or territorial health departments may recommend different timing for administration for their area.
  2. Getting an RSV antibody immunization for your baby if they are younger than 8 months and born during, or entering, their first RSV season. In rare cases, a healthcare provider may determine an RSV immunization is needed for an infant even though the mother received an RSV vaccine.

A dose of RSV antibody is also recommended for children between the ages of 8 and 19 months entering their second RSV season who are in at least one of these groups:

  • Children who have chronic lung disease from being born prematurely
  • Children who are severely immunocompromised
  • Children with cystic fibrosis who have severe disease
  • American Indian and Alaska Native children 

 

Questions

Q: Do you have any recommendations about coadministration?

Kathryn Edwards: The GSK studies included an influenza vaccine coadministration study, and when they were given together, there was a little bit of a diminution in the immune response to influenza, but it was certainly not inferior or met any kind of exclusion. I think you can give them together and that you do need to realize that these vaccines, particularly the GSK, does contain an adjuvant so if you give it with another adjuvanted vaccine such as Shingrix or another adjuvanted vaccine, which would be an influenza adjuvanted, sometimes you can get an additive effect in terms of a systemic adverse event. I think that it’s a delicate balance. You need to tell people that if they’re also getting the adjuvanted flu or if they’re getting COVID-19 vaccine, that they may be under the weather. You have to have compliant people but you also don’t want people to be upset because you didn’t tell them they might feel worse after vaccination if they get multiple vaccines.

 

Q: What do you say to providers who are saying that they want to delay the RSV vaccination to wait for more data to come out?

Kathryn Edwards: I think one that some of my colleagues that are healthy older adults are saying that they’re healthy and not going to get hospitalized because they don’t have any comorbidities. So they are just going to wait and see. I think that that is okay. If you have a comorbidity, particularly a chronic lung disease or diabetes, I think it would be best to get it. If you have no comorbidities, you may choose to wait. It’s a shared decision making recommendation for older adults, and just like with your kids you give them some options and then they can decide. If you have a COPD patient who said they won’t take it, I think you need to go over it with them. For people that are on the on the lower age range that have no comorbidities, it’s understandable if they want to wait.

 

Q: Were there any notable adverse events for the monoclonal antibody or for the maternal RSV vaccine in clinical studies?

Kathy Edwards: Yes, there were. There were two maternal vaccines studied—one was GSK and one was Pfizer. The studies both found more vaccinated women were delivering premature babies. For the maternal vaccine studies, mothers were given RSV vaccines anywhere from  24–36 weeks.  A study of RSV vaccination of pregnant women using the GSK vaccine found an unequal distribution of prematurity and infant deaths associated with the GSK vaccine in the very most premature babies. Because of that, GSK halted its studies and are not, at this time, perusing the GSK maternal vaccine. The Pfizer study also recruited people 24– 36 weeks gestation and there was a slight imbalance in the cases of prematurity. In the Pfizer study, the recipients of the vaccine were not statistically significant. It was noted but it was not a reason to derail the study or to stop the study. The FDA insisted upon not approving this maternal vaccination at 24 weeks but going to say that it can be given at 32–36 weeks. When they looked at pregnant women vaccinated only during 32-36 weeks’ gestation, the imbalance was no longer seen for prematurity. It also appeared that prematurity in infants whose mothers got RSV vaccine was much more commonly seen in the low- and middle-income countries and not so much in the high income. The monoclonal antibody studies have not shown that distribution, however, there are several monoclonal studies that are coming out. There is another study of another monoclonal by Merck and those studies will be coming out soon. There will be other monoclonals coming out. In the Merck study the monoclonal is being given to premature babies. That is also going to be looked at very carefully. The monoclonals will be standard of care. Babies that are premature are more likely to have cardiovascular disease or lung disease, so they’re going to have more adverse events whether they received the monoclonal or not, so that’ll be important to weigh the impact of monoclonal antibodies in premature infants.

 

Q: With regard to the Tdap and RSV vaccines, there are a lot of healthcare providers who may be thinking about how to organize vaccination during pregnancy. Would, in your judgement as a pertussis expert, recommend that we strategizes separating those two vaccines?

Kathy Edwards: There is a study that shows that there is a diminution in the pertussis antibody when it’s given to mothers along with the RSV vaccine. I don’t know that the titers are clinically meaningfully lower. I don’t know that there’s any evidence that there is a functional or biological difference that would impede the actual protection to the baby, but I think that it is possible to give the pertussis vaccine a little bit earlier. What you might want to do is give the pertussis vaccine at 27-32  weeks and then give the RSV vaccine at the 32–36 weeks. Giving both at the same time is a possibility if need be.

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