Webinar Ab Quant 30 Jan 2021

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Antibodi Kuantitatif:

Vaksin dan Plasma Konvalesen

Menempatkan pada Tempatnya

Tes Covid-19

@ 30/01/2021

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Infection volume 48, pages665–669(2020)

SARS CoV 2 Protein

Structure and Entry

into Human Cell

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Cells 2021, 10(2), 206;

https://doi.org/10.3390/cells10020206

Front. Microbiol., 19 October 2020 |

https://doi.org/10.3389/fmicb.2020.584251

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Pediatr Allergy Immunol. 2020;31:454–470.

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Front. Microbiol., 19 October 2020 | https://doi.org/10.3389/fmicb.2020.5 84251

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Pediatr Allergy Immunol. 2020;31:454–470.

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Fase Akut Keluar dari RS

8 pekan setelah sembuh Nature Medicine| VOL 26 | August 2020 | 1200–1204

International Journal of Infectious Diseases DOI: (10.1016/j.ijid.2020.09.1484)

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Dari 439 subyek, IgG tetap terdeteksi

sampai hari ke 115 sejak timbulnya

gejala, tanpa penurunan titer secara

signifikan.

Daya netralisasi memuncak

pada hari ke 31-45, diikuti

penurunan perlahan sampai

hari ke 105, dan turun secara

signifikan setelah hari ke 105

IgA dan IgM lebih cepat turun titernya

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Vaccines 2020, 8, 443. https://doi.org/10.3390/vaccines8030443

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Nature Reviews

Immunology volume 21, pages73–82(2021)

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Antibody-dependent Enhancement (ADE) ?

Fever, COVID-19 (SARS-CoV-2), and Antibody-Dependent Ulrich, H., Pillat, M.M. and Tárnok, A. (2020), Dengue Enhancement (ADE): A Perspective. Cytometry, 97:

662-667. doi:10.1002/cyto.a.2404

Nature Reviews Immunology volume 20, pages339–341(2020)

Rapid/

Qualitative

Semi/

Quantitative

Neutralization Test / svNT

PRNT

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N Engl J Med 2020;383:1544-55. DOI: 10.1056/NEJMoa2024671

The mRNA-1273 vaccine

candidate induced

antibody levels exceeding

those in human

convalescent-phase serum,

with live-virus reciprocal

50% inhibitory dilution

(ID50) geometric mean

titers of 501 in the 10-μg

dose group and 3481 in

the 100-μg dose group.

Pre-clinical Trials

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Lancet 2020; 396: 479–88

Phase 2 trials

AdenoV Vaccine

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Safety Faktor Keamanan menjadi penentu pertama dan utama Imunogenisitas Membentuk antibodi Bertahan lama Efikasi sakit Mencegah timbulnya gejala atau gejala yang berat Efikasi infeksi Mencegah terjadinya infeksi Masa Proteksi Berapa lama imunitas spesifik itu bertahan

Science 13 Nov 2020: Vol. 370, Issue 6518, pp. 763-765

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Membutuhkan uji klinik bertahap jangka panjang

(rata-rata 5-15 tahun), sulit dilakukan pada saat pandemi

Dilakukan beberapa uji klinik secara simultan, dengan

subyek dari sederhana sampai makin kompleks

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Efektivitas?

• Dibuktikan setelah penyuntikan pada masyarakat luas

• Diperlukan pengujian titer maupun daya netralisasi

• Belum didapatkan kesepakatan batas yang dianggap

memberikan proteksi optimal terhadap pencegahan

gejala atau pencegahan infeksi

• Diperlukan banyak data untuk menyepakati kadar

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Convalescent plasma in Covid-19: Possible mechanisms of action

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Niveditha Devasenapathy et al. CMAJ 2020;192:E745-E755 2020 Jul 6

Efficacy and safety of convalescent plasma for severe COVID-19 based on evidence in other severe respiratory viral infections: a systematic review and meta-analysis

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Niveditha Devasenapathy et al. CMAJ 2020;192:E745-E755 2020 Jul 6

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(Teguh, 2020)

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A Randomized Trial of

Convalescent Plasma in

Covid-19 Severe Pneumonia

https://www.nejm.org/doi/full/10.1056/NEJMoa2031304

November 24, 2020

DOI: 10.1056/NEJMoa2031304

Convalescent patients with a minimum SARS-CoV-2 total antibody titer of 1:400 (median 1:3200) were accepted as plasma donors after they had provided informed consent

Although baseline median titers were identical, patients receiving convalescent plasma had SARS-CoV-2 total antibody levels that were higher at day 2 than levels in

patients receiving placebo. No differences in antibody titers were noted at days 7 or 14

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Convalescent plasma with high IgG titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in

older adult patients within 72 hours after the onset of mild Covid-19 symptoms.

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Convalescent plasma with high IgG titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in

older adult patients within 72 hours after the onset of mild Covid-19 symptoms.

Donor titers with median titer of

1:3200

, showed a

relative risk reduction of 73.3%, in recipients of

antibody concentrations above the median

concentration

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S1 S1

RBD N

Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 26, No. 7, July 2020

SARS-CoV-2 Antibody Responses in

COVID-19 Patients

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• Patients with severe disease had higher peak PRNT

₉₀

and PRNT

₅₀

antibody titres than patients with mild

or asymptomatic infections.

• Age did not appear to compromise antibody

responses, even after accounting for severity.

• SARS-CoV-2 infection elicits robust neutralizing

antibody titres in most individuals.

Lau, E.H.Y., Tsang, O.T.Y., Hui, D.S.C. et al. Neutralizing antibody titres in SARS-CoV-2 infections. Nat Commun 12, 63 (2021). https://doi.org/10.1038/s41467-020-20247-4 04 January 2021

PRNT₉₀

PRNT₅₀

Titer Ab

Data Titer NAb minimal

sesuai hasil PRNT, belum

dipublikasikan

Neutralizing antibody

titres in SARS-CoV-2

infections

(Nature Communication)

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In this work, we aim to evaluate a

quantitative SARS-CoV-2 S1-RBD Ig

electro-chemiluminescence immunoassay (ECLIA)

In conclusion, a quantitative SARS-CoV-2 S1-RBD Ig assay offers favorable and sustained assay characteristics allowing the determination of quantitative associations between clinical characteristics (e.g., disease severity, smoking or fever) and antibody levels. The assay could also help to identify individuals with antibodies of non-S1-RBD specificity

with potential clinical cross-reactivity to SARS-CoV-2. Tonang Dwi Ardyanto

r = 0.97, 95% CI, 0.96–0.97

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The efficacy assessment of convalescent plasma therapy for

COVID-19 patients: a multi-center case series

Signal Transduction and Targeted Therapy (2020) 5:219 ;

https://doi.org/10.1038/s41392-020-00329-x 22 Desember 2020

34 donor, 248

products with

minimum titer

of

1:800

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Catatan/Rekomendasi

• Perlu disepakati patokan titer antibodi untuk calon donor, mengingat

kaitan dengan outcome dan parameter pemeriksaan terkait mulai

banyak tersedia

• Walau laporan masih bervariasi antara memberi sedikit manfaat atau

tidak signifikan, tapi laporan reaksi transfusi masih dalam angka yang

wajar, menandakan proses pemeriksaan pra-transfusi sudah

dilaksanakan

• Kesepahaman dengan pasien/keluarga untuk tidak menimbulkan

situasi tergesa-gesa dalam proses pemberian terapi plasma

konvalesen

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