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10/09/2020Gunilla Karlsson Hedestam
Covid-19 – antibody responses and vaccinesGunilla Karlsson Hedestam
September 9, 2020
Virues that infect the respiratory tract
Virus Infants/children Adolescents Adults Aged
Influenza virus +++ +++ ++++ ++++Rhinovirus +++ +++ ++ ++++RSV ++++ + + +Adenovirus +++ +++ ++ -Coronavirus +++ + + -
Relative importance in different age groups:
Endemic coronaviruses: 229E, HKU1, NL63, OC43 (common cold viruses)
10/09/2020Gunilla Karlsson Hedestam
New coronaviruses: a different story
SARS-CoV (2003) and MERS (2012), twobetacoronaviruses withpandemic potenial
SARS CoV-2: less pathogenic, more contagious
>25 million recorded cases>875,000 deaths
Lack of immunity in the population
Risk of severe disease is strongly correlated with age
Photo: Yanan LiAinhoa Moliner Morro and Siwen Long
10/09/2020Gunilla Karlsson Hedestam
How do antibody responses to a new emerging virus evolve in individuals and in the population?
Ab levels and types of responses in infected individuals Seroprevalence estimates in the population Protective immunity and durability Benchmark information to guide selection of vaccine platforms
10/09/2020Gunilla Karlsson Hedestam
An unprecedented interest in antibodies
Apoteket, Werlab, Synlab, KRY and others
A range of commercially available platforms and investigator-driven lab-basedassays were developed rapidly, of varying standards.
The nature of the assay, as well as the sub-population sampled, must be considered in seroprevalence studies.
What frequency of the Stockholm population has developed antibodies?
7%, 12%, 17%, 20% or more?
10/09/2020Gunilla Karlsson Hedestam
SARS CoV-2 and the importance of the virus spike protein
Structure of the SARS CoV-2 spike protein. Wrapp et al. Science 2020
The spike binds the cellular receptor, ACE2 The spike is a central target for neutralizing antibodies
CoV-2 spike produced at KI by Leo Hanke
SARS CoV-2 spike (S) glycoproteins
Wrapp et al.
Spike
Photo: Yanan Li
Laura Perez Vidakovics and Leo Hanke
The spike protein was used to set up a binding assay for antibody detection
10/09/2020Gunilla Karlsson Hedestam
Antibody (Ab) levels to SARS CoV-2 varied but all persons with symptoms developed antibodies
Anti-S IgG
https://www.medrxiv.org/content/10.1101/2020.07.17.20155937v2
Xaquin Castro DopicoSoo AlemanJan Albert
10/09/2020Gunilla Karlsson Hedestam
SARS CoV-2 antibody isotypes in different disease severity
Category 1: seeked medical care but were not admitted
Category 2: were admitted but did not need ICU care
Category 3: were admitted to the ICU
IgM IgG IgA
10/09/2020Gunilla Karlsson Hedestam
SARS CoV-2 antibody in healthy donors
Controls 2019 (C)n = 295
PCR+ cohortn = 105
Blood donors (BD)n = 1000
Pregnant women (PW)n = 900
Anti-S IgG
10/09/2020Gunilla Karlsson Hedestam
SARS CoV-2 serology in Stockholm week 14-25
Anti-S
Blood donors Pregnant women
7% early summer12% end of summer
Far from herd immunity
Do people ”loose” their antibodies? Antibodies decline with time, but memory B cells perists
Photo: Yanan Li
Memory B cells do not produce antibodies, they circulate and survey the body for news signs of infection
Reactivation of memory B cells by a second exposure triggers antibodyproduction again
10/09/2020Gunilla Karlsson Hedestam
Do antibody tests reflect how many persons have been infected?
Virus spread is currently low in Sweden
What is the basis for this given the relatively low seroprevalence?
Some exposures may result in a sub-clinical, transient infectionagainst which the innate immune system is highly effective in controlling the virus. Suchinfections may be missed by PCR and antibody testing.
Public health measures such as social distancing and implementation of strict hygien routines, especially when caring for highly susceptible persons, are effective and are paying off.
Additional factors such as cross-reactivity betweenSARS CoV-2 and endemicCoVs, T cells or local Absmay contribute to some levelof immunity. Virus evolution may also be a factor.
10 september 2020Gunilla Karlsson Hedestam
VaccinesNeutralizing antibodies mediate the protective effect of almost all existing vaccines
Correlates of protection induced by vaccination Plotkin, Clin Vaccine Immunol. 2010 July; 17(7): 1055–1065
DiphtheriaHepatitis A virusHepatitis B virusHuman papillomavirusInfluenza virusJapanese encephalitis virusMeasles virusMumpsPertussisPolio virusRabies virusRotavirusRubellaTetanusSmallpoxTick-borne encephalitis virusVaricellaYellow fever virus
Photo: Yanan Li
How are vaccines made?
Inactivated virusPolio, Tickborne encephalitisRabies, Hepatitis A
Attenuated virusMeasles, Rubella, Mumps,Yellow fever
Protein subunitsInfluenza, Hepatitis B, Papillomavirus (HPV)
DNA or RNA vaccin (experimental)
Viral vectors: Cold viruses that carry CoV-2 genes (experimental)
Types of vaccines
Sinovac Biotech
Novavax, Sanofi, GSK/Clover
Moderna, CureVac, BioTech (RNA)Inovio (DNA)
AstraZeneca, J&JSputnik
SARS CoV-2 vaccine candidates
10/09/2020Gunilla Karlsson Hedestam
Acknowledgements
Xaquin Castro DopicoPradeepa PushparajMonika ÁdoriDarío Solís SayagoMarco MandolesiMartin CorcoranSharesta KhoenkhoenUta HardtMateusz KadukSanjana NarangMark Chernyshev
Ben MurrellDan ShewardMurray ChristianChangil Kim
Jonathan CoquetPia DosenovicJoanna Rohrbach
Gerry McInerneyLeo HankeLaura Perez VidakovicsAinhoa Moliner MorroSiwen Long
Jan AlbertTobias AllanderSandra MuschiolGordana BogdanovicRobert DyrdakKarin BlomqvistMalin Grappe
University of CambridgeChris WallaceNastasiya F. Grinberg
Soo AlemanJoakim DillnerMattias Forsell