Daya Proteksi Antibodi

Terhadap infeksi SARS CoV-2

Rudi Wisaksana
Tim PINERE
KSM Ilmu Penyakit Dalam
RSUP Dr. Hasan Sadikin Bandung
High level of Antibody Netralization / anti S-
RBD Provide protection to COVID-19
• Fishing boat 122 crew
• 3 person have had COVID-19  High NAB and RBD Ab
• COVID-19 outbreak on the ship
• 104/122 (83.2%) had COVID-19 illness
•  The trhee person did not get COVID-19

Addetia A, J. Clin. Microbiol, Oct 2020

Neutralizing Ab: The Superheroes…
Antibody Type and Relevance
Ab Main Types Early / Immature Mature Neutralizing
Descriptions • Appear in early • Appear in • Appear in immunity /
infection phase convalescence phase convalescence phase
• Do not effective • Effective recognize • Effective neutralize
recognize the virus virus Virus

Example • IgM, early/immature • Late / mature Igs • Neutralizing

IgA, IgG Antibodies (subset of
mature Igs)
Relevance / Purpose • Initial host response to • Host memory for • Render the virus
understand the virus future recognition ineffective against the
host

www.britannica.com
• Meta-analysis
• 150 studies

• Median time to
Seroconversion
• IgG: 12-15 days
• IgM: 4-14 days
• IgA: 2-24 days
Faktor-faktor yang mempengaruhi NAb
• COVID-19 berat berhubungan
dengan peningkatan produksi Ab
dan Titer Netralisasi
• Potensi NAb berhubungan dengan
prognosis

• Faktor individu
• Umur, Gender, Komorbid?
Neutralizing Antibodies Apps
• Active Immunization
• Vaccination
• Infection

• Passive Immunization
• Plasma Convalescent
• Hyperimmune IgG
• Monoclonal Antibodies
61 SARS CoV 2 neutralizing monoclonal antibodies from 5 patients
19 of these had potent neutralizing activity in vitro against SARS CoV 2
Epitope mapping showed equal distribution against RBD & N terminal Domain
2 Nab recognized epitopes that overlap domains at the top of spike

Liu L et al. Nature 2020; 584; 450

Against Variants
• Animal Study: 4 rabbits
• Heterologous Prime Boost:
• DNA Vaccine
• Protein Recombinant
• Rabbit Monoclonal antibodies
could neutralize:
• Wild type virus
• Variants: D614G, B.1.1.7,
B.1.429, P.1, B.1.526, and
B.1.351
Teknik menentukan kadar netralisasi antibody
 Validasi FastBio-RBDTM
Menggunakan Subjek Penelitian iCovid dan CovNAb
Fast BioRBD menunjukkan kesetaraan yang baik dengan Uji SVNT. Namun masih terkendala dengan
tercampurnya sampel penyintas dan paska vaksin
Projection of cut off level of IgG Anti RBD (28 days
post vaccine) Related to Protection Efficacy
50% 60% 70% 80% 90%

BAU (1) 18 50 165 506 2360

roche
18.5 51.4 169.8 520.6 2,428
(0.972)
Abbott
126 352 1,162 3,563 16,619
(0.142)
FastBioRBD
0.9 2.5 8.3 25.3 118.0
(20.0)
Siemens
0.8 2.3 7.6 23.2 108.2
(21.8)
BAU=Binding Antibody Unit
Shuo Feng , medRxiv preprint
doi: https://doi.org/10.1101/2021.06.21.21258528
Predicted duration of immunity varies with initial
efficacy
• Assuming
neutralization is major
mechanism of
protection
• Initial efficacy of 95%
expected to maintain
high efficacy (77%)
after 250 days
• 70% efficacy may drop
to 33% after 250 days
Khoury et al. Nature Medicine (2021)
Pemeriksaan Antibodi Tenaga Kesehatan RSHS
• Cross Sectional
• Kuesioner
online
• Pemeriksaan
Juli 2021: 4-5
bulan pasca
vaksinasi
Kadar IgG Anti-RBD pada Nakes RSHS
• Kohort Tenaga Kesehatan RSHS: 630 subyek
• Median umur: 39 tahun
• Gender: Pria 39,6%; Wanita 60,4%
• Profesi:
• Dokter 54,7%, Perawat/Bidan: 14,7%
• Penunjang: 8,7%
• Zone Kerja
• Merah 33,1%; Kuning 40,2%, Hijau 26,7%
• Vaksinasi Lengkap: 96,3%
• Riwayat COVID-19: 23,9%
 Kadar IgG Anti-RBD pasca Sinovac
70% 80% 90%
• Median waktu sejak
vaksinasi (Sinovac)
166 hari (IQR: 140-172)

• Median Kadar IgG

87,8 BAU (IQR: 27,3-677,1)
Proteksi Ig Anti RBD N (%)
> 90% 23 (3,6)
> 80% 155 (24,6)
> 70% 233 (36,9)
 Kadar Anti-RBD pada Antibodi Menurut Umur* Antibodi Menurut Gender* Antibodi Menurut Profesi
berbagai karakteristik 4000 4000 4000
subyek

Anti-RBD (BAU/mL)
3000 3000 3000

Anti-RBD (BAU/mL)
Anti RBD (BAU/ml)
2000 2000
500

400 400
400
300

200 200
200
100

0 0
0
<60 thn >60 thn

at

in
Male Female

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Antibodi Menurut Vaksinasi* Antibodi Menurut Zona* Antibodi Menurut Komorbid Antibodi Menurut Riwayat Infeksi*
4000
4000 4000 5000
3000
Anti RBD (BAU/ml)

3000 3000

Anti-RBD (BAU/mL)

Anti RBD (BAU/ml)

Anti-RBD (BAU/mL)

2000 4000
500 2000 2000
500 500
400 3000
300 400 400

200 300 300 2000

100 200 200

1000
0 100 100
0
ap
ap

0
CovNAb, 2021 0
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Tidak Ya
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No Yes
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Kejadian Infeksi SARS CoV-2
Karakteristik Riwayat Infeksi Tidak Terinfeksi p value
Umur Median, tahun (IQR) 39 (32-49) 38 (32-50) 0,916
Gender Pria, n (%) 59 (25,0) 177 (75,0) 0,335
Wanita, n (%) 78 (21,6) 283 (78,4)
Profesi Dokter, n (%) 95 (35,2) 175 (64,8) <0,0001
Perawat, n (%) 16 (21,9) 57 (78,1)
Penunjang, n (%) 2 (4,8) 40 (95,2)
Lain, n (%) 7 (7,0) 93 (93,0)
Zona Merah, n (%) 42 (23,9) 134 (76,1) 0,034
Kuning, n (%) 38 (16,6) 191 (83,4)
Hijau, n (%) 40 (27,4) 106 (72,6)
Komorbid Ada, n (%) 33 (25,2) 98 (74,8) 0,536
Tidak, n (%) 101 (22,6) 346 (77,4)

CovNAb, 2021
Median waktu hingga
infeksi SARS CoV-2
adalah 129 (IQR 99-146)
hari

CovNAb, 2021
Riwayat Infeksi SARS CoV-2 dan Vaksinasi

Riwayat Infeksi Tidak ada Riwayat

Infeksi

Vaksinasi Lengkap 137 (22,9%) 461 (77,1%)

Vaksinasi Tidak 11 (52,4%) 10 (47,6%)

Lengkap

Efficacy Vaksin = 56,3% p=0,02

CovNAb, 2021
Perbandingan kadar antibody RBD
Tenaga Kesehatan RSHS vs Pasien CKD dan ODHA

Efficacy 64,4%
(p=0,027)

CovNAb, 2021
Pre dan Post Vaksinasi Ketiga
Paired Data • Pasca Vaksinasi Ketiga (Moderna)
• Pemeriksaan 1 bulan sesudah
10000

1000
vaksinasi
• Proteksi Anti RBD > 90% ditemukan
Anti-RBD (BAU/mL)

100
pada 85,9% subyek
10 • Tidak ada perbedaan antar
kelompok
1
• Pemeriksaan akan dilanjutkan pada
0.1
bulan 3, 6, dan 12
Pre Post
Waktu Pemeriksaan

CovNAb, 2021
Take Home Messages….
• Neutralizing Antibodies are The Super Heroes…
• Works for COVID-19 prevention and also
treatment
• Best prevention can be achieved by vaccination
• Individual response need further explore
Terima Kasih
• Tim PINERE
• Dr Yovita Hartantri
• Tim CoVNAb
• Dr. Bachti Alisjahbana
• Dr. Agnes Indrati
• Dr. Marita
• Dr. Sasfia
• Instalasi Laboratorium
• Dr. Delita Prihatni
• Keluarga Besar RSUP Dr. Hasan Sadikin
CovNAb, 2021
Perbedaan kadar antibodi pada Subyek sehat dan dengan
Komorbid, 1 dan 3 bulan setelah vaksinasi Sinovac

Pemeriksaan kadar RBD pada subyek penerima vaksin Sinovac 1 bulan dan 3 bulan
memberikan hasil yang positif rendah. Lebih rendah ditemukan pada penderita Geriatri
 Abbott
0.142

Roche 1 Siemens
0.972 BAU/ml 21.8

FastBioRBD
20.0

Conversion of Arbitrary Unit to Binding Antibody Unit (BAU)

Heterologous Ebola Vaccine
• Randomised, observer-blind, placebo-
controlled, phase 2 trial in France and
UK
• Heterologous vaccination regimens
• Adenovirus type 26 vector-based vaccine
(Ad26.ZEBOV), expressing Zaire Ebola
virus glycoprotein
• Non-replicating, recombinant, modified
vaccinia Ankara (MVA) vector-based
vaccine, encoding glycoproteins from
Zaire Ebola virus, Sudan virus, and
Marburg virus, and nucleoprotein from
the Tai Forest virus
• Safe, well tolerated, and immune
responses persisting for 1 year
Heterologous could be
reactogenic…
• Com-CoV Study: UK, 830 participants
• Four Arms:
• ChAD/ChAD
• ChAD/BNT
• BNT/BNT
• BNT/ChAD
• Both heterologous vaccine schedules
induced greater systemic
reactogenicity
 Kadar Antibodi Tenaga Kesehatan RSHS
Sebelum dan 1 Bulan Setelah Vaksinasi Moderna

• Pemeriksaan pada
Tenaga Kesehatan di
RSHS
• Pemeriksaan berulang
menunjukkan
peningkatan kadar
RBD yang bermakna
dengan Booster
Moderna
Immunogenicity and Safety

• Four Trials: 1862 participants

• Europe: Germany, UK, Spain
• Homologous vs. Heterologous Prime-
Booster:
• ChAd, BNT, ChAd/ChAd, BNT/BNT,
ChAD/BNT, BNT/ChAD
• Homologous BNT162b2 and heterologous
ChAd/BNT had the highest antibody titers
• Heterologous ChAd/BNT had the highest T
cellular responses
• Higher neutralizing activities against
variants of concern B.1.1.7, B.1.351, and
B.1.617 observed in heterologous
ChAd/BNT vaccinations
Kadar Anti-RBD pada Antibodi Menurut Umur* Antibodi Menurut Gender* Antibodi Menurut Profesi
berbagai karakteristik 4000 4000 4000
subyek

Anti-RBD (BAU/mL)
3000 3000 3000

Anti-RBD (BAU/mL)
Anti RBD (BAU/ml)
2000 2000
500

400 400
400
300

200 200
200
100

0 0
0
<60 thn >60 thn

at

in
Male Female

te

an
w

-la
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ra

nj

in
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Pe

nu

La
Pe
Antibodi Menurut Zona* Antibodi Menurut Komorbid Antibodi Menurut Obesitas
4000 4000 4000
3000

Anti-RBD (BAU/mL)
3000 3000

Anti-RBD (BAU/mL)
Anti-RBD (BAU/mL)

2000 2000 2000

500 500 500

400 400
400
300 300
300
200
200 200
100
100 100
0
0 0
No Yes
No Yes
CovNAb, 2021
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