what you need to know about covid-19 vaccine
TRANSCRIPT
What you need to know about COVID-19 vaccine
Presented by:
Wilbur H. Chen, MD, MS, FACP, FIDSACenter for Vaccine Development and Global Health
University of Maryland School of Medicine
Today’s Moderator & CITI Program
The Collaborative Institutional Training Initiative (CITI Program) is dedicated to promoting the public’s trust in the research enterprise by providing high quality, peer-reviewed, web-based educational courses in research, ethics, regulatory oversight, responsible conduct of research, research administration, and other topics pertinent to the interests of member organizations and individual learners.
About Today’s Presenter
Wilbur H. Chen, MD, MS, FACP, FIDSAProfessor of MedicineCenter for Vaccine Development and Global HealthUniversity of Maryland School of Medicine
Adult infectious disease physician-scientist specializing in developing vaccines. Dr. Chen serves on advisory committees with NIAID, CDC, and NFID for his expertise on vaccines.
Conflicts of Interest Disclosure: Wilbur Chen
I have no relevant personal/professional/financial relationship(s) with respect to this educational activity.
Learning Objectives
• Review the vaccine candidates for COVID-19• Describe the process of vaccine
development through approval• Discuss the policy decision making
process for COVID-19 vaccination• Address some of the most common
concerns regarding COVID-19 vaccines
Recent History of Emerging Infections
H5N1SARS
West Nile
NipahDengue
H3N2v
MERSH7N9
EbolaChikungunya
Zika
Hendra
H1N1pdm2019-nCoV
Ebola
Hendra 1994H5N1 1997Nipah 1998West Nile (Americas) 1999SARS-CoV 2003H1N1pdm 2009H3N2v 2011MERS-CoV 2012H7N9 2013Chikungunya (Carib) 2013Ebola (W. Africa) 2014Zika (Americas) 2015Dengue (Americas) 2016Ebola (Central Africa) 2018SARS-CoV-2 2019
Coronaviruses, they’re in bats normally
Endemic in bats
?Humans
Intermediate Host
Image source: Coronaviridae Study Group of the International Committeeon Taxonomy of Viruses in Nature Microbiology (10.1038/s41564-020-0695-z); Adapted and used with permission under CC BY 4.0
Phylogeny of Coronaviruses
Human common colds
Human outbreak 2012
Human outbreak 2003
Human outbreak 2019
Vaccine Development Through Implementation
Public Health Need / Market Need
Political Will
- Pathogenesis- Immunity- Antigen Discovery- Animal Models
- Vaccine Design- Formulation- Safety/Toxicity- Proof of Concept
- Assay Development- Process Development
- Scaling Up Manufacture- Quality Controls
- Safety & Reactogenicity
- Immunogenicity
- Efficacy
Vaccine Platforms (Discovery Phase)
Traditional Approach
Newer ApproachesCell Culture
Pow! Adjuvants
Virus-like particles, Virosomes, Nanoparticles
Virus vectored
Recombinant
DNA/mRNA
Live attenuated
Future Approaches
SARS-CoV-2 virus genome sequence, available January 10, 2020 (GenBank)
Genomic sequence available at: https://www.ncbi.nlm.nih.gov/nuccore/MN908947Image source: Mousavizadeh and Ghasemi in the Journal of Microbiology, Immunology and Infection (10.1016/j.jmii.2020.03.022); Used with permission under CC BY-NC-ND 4.0
COVID-19 Vaccines
Pfizer Moderna AstraZeneca†Johnson&Johnson Novavax
BNT162b2 mRNA-1273 AZD1222 Ad26.COV2.S NVX-CoV2373U.S. U.S. U.K. (U.S.) U.S. U.S.
95% 94.1% 62-90% 57-72% 49-90%
mRNA mRNA Virus-vector, ChAd
Virus-vector,Ad26
[single dose]
Nanoparticle adjuvant
Gamaleya Vektor CanSino Sinovac Sinopharm SIILP Bharat CadilaSputnik V EpiVacCorona Convidicea Coronavac BBIBP-CorV Covishield* Covaxin -
Russia Russia China China China India India India
91.6%Immunol
100%95% 50-78% 79% 62-90% 60-70% n/a
Virus-vector,Ad26 & Ad5
peptide Ad5
[single dose]
Vero cell culturewith AlOH3
Vero cell culturewith AlOH3
Virus-vector,ChAd
Cell culture, Alhydroxiquim
-II
Plasmid DNA
U.S. Vaccines
Global Vaccines
Phases of Development
• Pre-Clinical Animal Models (before entering humans)• Phase 1 – Safety (n=100)• Phase 2 – Safety and Immunogenicity (n=100s to 1000s)• Phase 3 – Safety and Efficacy (n=10,000s)
U.S. FDA: Guidance for Licensure of COVID-19 Vaccines(June 2020)• Populations – generalizable, including high-risk populations• Efficacy:
o prevent symptomatic, lab-confirmed infectiono if possible, prevent more severe infections (e.g., respiratory or kidney failure)
• Statistics – minimum 50% efficacyhttps://www.fda.gov/regulatory-information/search-fda-guidance-documents/development-and-licensure-vaccines-prevent-covid-19
What do we learn on the Safety of the vaccine?
Common Side Effects• Injection site reactions
Pain, swelling, redness, bruising
• Systemic reactionsHeadache, muscle ache, fever, fatigue
Some Less-Common Side Effects• ≥1 case per 10,000
Cannot identify:• Very rare side effects
e.g., 1 case per million
• Long-term side effectse.g., something that will occur after 2 years
How can you tell if it is related to the vaccine?v Compare rates between vaccine and placebov Compare rates in general population
How do you measure Efficacy?
Primary EfficacyPrevention of moderate illness• “Moderate” symptoms
Fever, cough, sore throat, chills, shortness of breath, muscle pain, diarrhea, vomiting, loss taste/smell
• Lab test positive PCR test within 4 days of symptoms
Other ways to measure Efficacy:• Prevention of “severe” illness• Prevention of hospitalization• Prevention of other major
complicationse.g., mech vent, ICU, organ failure
• Prevention of death
• Prevention of asymptomatic illness• Prevention of transmission
How are we moving so fast?
2-5 yrs 2 yrs 2 yrs 5 yrs
$ $$ $ $$ $$$ $$$TimeMoney
Total:10-15 years$100s Millions
“normal” circumstances
PANDEMICcircumstances
Scale-UpManufacturing Development Large Scale Manufacture
Manufacturing Development Scale-Up Large Scale
Manufacture
12-18 mons
U.S. Gov’t investments of $Billions
$ $$ $$$
DeliveryPhI
Ph II
Ph III
DiscoveryPreclinical
Vaccine Policy
• Limited Supply Allocationo Prioritization to the Highest Risk Populations (HCP, essential workers, etc.)o Maximization of Utility o Equitability & Ethics framework
• National Guidelines vs. Local Jurisdictional flexibility• Access & Distribution (Logistics)• Public Health Value & Public Trust
v Maximize benefits, minimize harms, equity, justice, fairness, transparency, evidence based (data driven), feasible
Vaccine Implementation
No.
Vac
cine
Dos
es A
vaila
ble
Initial PhaseLimited vaccine available
Next PhasePlenty vaccine available
Final PhasePlenty vaccine available
Strategy:Highly targeted immunization in priority populations
Strategy:Surge capacity and use of innovative, broad-based delivery
Strategy:Continued increasing access, to immunize those not yet vaccinated
Prioritization of the population, based on Risk
Total U.S. population ~330 million:• Healthcare Personnel (20M)• Long-Term Care Facility residents (3M)• Essential Workers*
• Frontline (27M)• Other (60M)
• Older Adults• 75+ (21M)• 65-74 (31M)
• Adults (18-64) with High-Risk Medical Conditions (>100M)
First responders, food & agriculture, education, manufacturing, corrections, transportation & logistics, food service
Energy, IT & communications, finance, media, legal, construction, public safety
*defined by Homeland Security (DHS) Cybersecurity and Infrastructure Security Agency (CISA)
Perception of “Value” of vaccines
Benefits:• Direct protection• Indirect protection (unvaccinated)• Spare healthcare costs• Increase work productivity• Safer travel, opening business
sectors• Enhance health equity• Stabilize society
Risks:• Short-term, self-limiting side
effects (<3 days)• Very rare, but treatable severe
allergic reaction• Time/cost of vaccination visit• Fear/Suspicion of serious or long-
term side effects
Vaccine Hesitancy
• Fear unknown• Distrust (history of unethical research)• False Information• Politicization of issues• Anti-vax sentiments (pre-date pandemic)
Pew 03Dec2020. “Majority of Americans now say they would get a vaccine for the coronavirus.” Pew Research Center, Washington, D.C. (2020)
Gallup 08Dec2020. “Willingness to Get COVID-19 Vaccine Ticks Up to 63% in U.S.” Used with permission from Gallup.com (Brenan 2020).
37-39% would NOT get vaccinated(December 2020)
Special Populations
Immunocompromised (studies to be started for vector-based vaccines)• mRNA vaccines can be given to immunocompromised
Pregnant & Breastfeeding Women (studies in progress)• No safety concerns from limited animal studies• mRNA vaccines can be given to pregnant & breastfeeding women
Children• Adolescents, 12-17 years (studies in progress)• K-6 grade Children, 5-11 years (studies to be started)• Infants & Toddlers (studies to be started)
Effect of Variant Viruses
• UK, B.1.1.7 virus• S. Africa, B1.351 virus• Brazil, P.1 virus
Image Source: Khan Academy; Adapted and used with permission under CC BY-SA 3.0.
Effect of mutation(s) on virus:• No Effect• Decreased “fitness”• Increased “fitness”
o Better transmissiono Higher severity of illnesso Evasion of:
§ Diagnostic Testing§ Therapeutics (Monoclonal
antibody)§ Vaccines
Glasses Mustache Scar
Other Important Questions to be Answered
Delayed Second Dose of Vaccine (studies in progress)• Second dose given 6 weeks, 12 weeks, or later• Allows for more first doses to be given
Mixed Dosing of Vaccines (studies to be started)• First dose mRNA vaccine with a second dose using a different mRNA vaccine
“Booster” Dose with a Variant Virus Vaccine (studies to be started)• Can booster vaccines catch-up with the changing landscape of variant
viruses?
We continue to monitor Safety
Post-Market Surveillance commitment required by FDA• VAERS (vaccine adverse event reporting system)• NHSN (national healthcare safety network)• CISA (clinical immunization safety assessment project)• Large-linked database systems
VSD (vaccine safety datalink), CMS, VA EHR
• V-SAFE (vaccine safety assessment for essential workers)Voluntary smartphone-based monitoring, text messaging
Why do you play a critical role?
“Vaccine Ambassador”• Promote vaccines with confidence• Know common questions and concerns• Engage in “healthy” discussion• Build trust
Other Considerations for Vaccination Program Support
• Vaccine Storage & Handling• Inventory Management• Vaccine Preparation & Administration Documentation• Data Reporting
o State and Federal Requirementso Central database
• Designing a Safe Environmento Crowd Control with Physical Distancingo Monitoring for Side Effects (management of anaphylaxis)
• Community Engagement
Continue Mitigation and Control Measures
• Wear a mask• Wash your hands• Watch your distance
• Stay home when sick, minimize circulation in public
• Maintain medical system capacity• Continue to make testing widely
available with prompt case contact tracing
PPE
Administrative Changes
Physical Distancing
Telework, Tele-education, Telehealth
Less
Mor
e
Infe
ctio
n Pr
even
tion
Effe
ctiv
enes
s
Wrap Up
• There are many vaccine candidates for COVID-19• The process for vaccine development
through approval was rapid, but safe• The policy decision making process for
COVID-19 vaccination carefully considers justice and equity• Addressing people’s concerns wins trust
and confidence in vaccination
Additional Resources
• Planning Information: https://www.cdc.gov/vaccines/covid-19/planning/index.html
• Vaccination Training Modules: https://www.cdc.gov/vaccines/covid-19/training.htmlhttps://openwho.org/courses/covid-19-vaccination-healthworkers-enhttps://www.naccho.org/blog/articles/covid-19-vaccination-training-programs-for-healthcare-professionals
• More Vaccine FAQs:https://www.cdc.gov/coronavirus/2019-ncov/vaccines/faq.html
Thank Youwww.citiprogram.org