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