Frågedatum: 2021-03-31
RELIS database 2021; id.nr. 452, ULIC
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Frågedatum: 2021-03-31 RELIS database 2021; id.nr. 452, ULIC


Provtagning av Ig-G antikroppar mot covid-19

Fråga: Jag undrar om man kan provta om en patient har Ig-G antikroppar mot Covid-19 för att säkerställa effekt efter vaccination mot covid-19 (liknande efter vaccination mot rubella)?

Svar: SAMMANFATTNING
I de fas 3-studier som har genomförts av de idag godkända vaccinerna mot Covid-19 var utfallsmåttet andelen insjuknade i Covid-19, och inte antikroppssvar på vaccin. Det är därför oklart om ett positivt antikroppstest ger hela svaret på om vaccinet skyddar. Det går idag inte heller att avgöra hur stor roll immunfaktorer som vi inte kan mäta spelar, till exempel cellulär immunitet.

Det är inget som hindrar den enskilda individen från att göra ett antikroppstest efter vaccination. Dock måste man vara säker på att testet man tar även mäter antikroppar mot spikeprotein, inte bara mot nukleokapsiden. De flesta tester i sjukvården borde vara ok ur det hänseendet, men kommersiella tester kan vara mindre lämpliga. Sammanfattningsvis är det möjligt att mäta antikroppar, men med dagens metoder kan man inte få en fullständig tolkning av svaret. Folkhälsomyndigheten håller just nu på att ta fram ett underlag

SVAR
I de fas 3-studier som har genomförts av de idag godkända vaccinerna mot Covid-19 var utfallsmåttet andelen insjuknade i Covid-19, och inte antikroppssvar på vaccin (1-3). Det är därför oklart om antikroppssvar eller cellulär immunitet kan användas som markör för vaccineffekt. Det har dock genomförts fas-1-studier av antikroppssvar och cellulär immunitet, och dessa redovisas nedan. Hur dessa resultat översätts till klinisk effekt är dock idag inte klarlagt.

The BioNTech-Pfizer COVID-19 Vaccine (also referred to as BNT162b2)

According to the first report on BNT162b1 vaccine from BioNTech-Pfizer immunogenicity (4), because the titre at which human neutralizing antibodies are protective remains unknown, these findings reported are not proof of vaccine efficacy. However, the kinetics and durability of the neutralizing titres are being monitored (4). Immunogenicity data from 45 healthy adults;18–55 years of age, from the placebo-controlled, observer-blinded USA trial, dosages of 10 µg, 30 µg (prime and boost doses 21 days apart for both dose levels) and 100 µg (prime only), were available (4). Receptor-binding domain (RBD)-binding immunoglobulin G (IgG) concentrations and SARS-CoV-2 neutralising titres in sera increased with dose level and after the second dose. For all doses, small increases in SARS-CoV-2-neutralizing geometric mean titres (GMTs) were observed 21 days after the first dose. Substantially greater serum neutralizing GMTs were achieved 7 days after the second 10-µg and 30-µg dose, reaching 168–267. Neutralizing GMTs further increased by 14 days after the second dose to 180 (10-µg dose level) and 437 (30-µg dose level), compared to 94 for the panel of human convalescent sera. Fourteen days after the boost dose, geometric mean neutralising titres reached 1.9- to 4.6-fold those seen in a panel of COVID-19 human convalescent sera (4

The antibody and T cell responses after vaccination with BNT162b1 from a second, non-randomized open-label phase I/II trial in 60 healthy adults, 18–55 years of age was reported from a Germany trail (5). Two doses of 1–50 µg of BNT162b1 elicited robust CD4+ and CD8+ T cell responses and strong antibody responses, with RBD-binding IgG concentrations clearly above those seen in serum from a cohort of individuals who had recovered from COVID-19. Geometric mean titres of SARS-CoV-2 serum-neutralizing antibodies on day 43 were 0.7-fold (1-µg dose) to 3.5-fold (50-µg dose) those of the recovered individuals. Most participants had T helper type 1 (TH1)-skewed T cell immune responses with RBD-specific CD8+ and CD4+ T cell expansion. Interferon-? was produced by a large fraction of RBD-specific CD8+ and CD4+ T cells. The robust RBD-specific antibody, T cell and favourable cytokine responses induced by the BNT162b1 mRNA vaccine suggest that it has the potential to protect against COVID-19 through multiple beneficial mechanisms (5).

Moderna COVID-19 Vaccine/mRNA-1273

Immunogenicity was reported in a phase 1, dose-escalation, open-label trial including 45 healthy adults, 18 to 55 years of age, who received two vaccinations, 28 days apart, with mRNA-1273 in a dose of 25 µg, 100 µg, or 250 µg. There were 15 participants in each dose group (6). After the first vaccination, antibody responses were higher with higher dose (day 29) with geometric mean titer [GMT], 40,227 in the 25-µg group, 109,209 in the 100-µg group, and 213,526 in the 250-µg group. After the second vaccination, the titers increased (day 57), GMT, 299,751, 782,719, and 1,192,154, respectively. After the second vaccination, serum-neutralizing activity was detected in all participants evaluated, with values generally similar to those in the upper half of the distribution of a panel of control convalescent serum specimens (6).

The 25-µg and 100-µg doses elicited CD4 T-cell responses involving type 1 helper T cells. CD8 T-cell responses to S-2P antigen were detected at low levels after the second vaccination in the 100-µg dose group.

Immunogenicity data for the mRNA-1273 vaccine in an expansion of the phase 1 trial among healthy participants who were 56 years of age or older were reported by Anderson EJ et al (7). Binding- and neutralizing-antibody responses appeared to be similar to those previously reported among vaccine recipients between the ages of 18 and 55 years and were above the median of a panel of controls who had donated convalescent serum. The vaccine elicited a strong CD4 cytokine response involving type 1 helper T cells.

The Oxford University-AstraZenec ChAdOx1 nCoV-19 vaccine

There are immunogenicity results from the phase 1/2 UK study, in 1077 healthy adults aged 18–55 year (8). Spike-specific T-cell responses peaked on day 14 (median 856 spot-forming cells per million peripheral blood mononuclear cells, IQR 493–1802; n=43). Anti-spike IgG responses rose by day 28 (median 157 ELISA units [EU], 96–317; n=127), and were boosted following a second dose (639 EU, 360–792; n=10). Neutralising antibody responses against SARS-CoV-2 were detected in 32 (91%) of 35 participants after a single dose when measured in MNA80 and in 35 (100%) participants when measured in PRNT50. After a booster dose, all participants had neutralising activity (nine of nine in MNA80 at day 42 and ten of ten in Marburg VN on day 56). Neutralising antibody responses correlated strongly with antibody levels measured by ELISA (R2=0·67 by Marburg VN; p<0·001).

The immunogenicity results from a phase 2 cohort in older adults (=56 years) (9) were reported to show similar immunogenicity.

Referenser:
  1. Commissioner O of the. Pfizer-BioNTech COVID-19 Vaccine. FDA [Internet]. 01 december 2021 [citerad 13 januari 2021]; Tillgänglig vid: https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/pfizer-biontech-covid-19-vaccine
  2. Commissioner O of the. Moderna COVID-19 Vaccine. FDA [Internet]. 01 juni 2021 [citerad 13 januari 2021]; Tillgänglig vid: https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/moderna-covid-19-vaccine
  3. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK - PubMed [Internet]. [citerad 13 januari 2021]. Tillgänglig vid: https://pubmed.ncbi.nlm.nih.gov/33306989/
  4. Mulligan, M. J. et al. Phase 1/2 study of COVID-19 RNA vaccine BNT162b1 in adults. Nature https://doi.org/10.1038/s41586-020-2639-4 (2020).
  5. Sahin, U., Muik, A., Derhovanessian, E. et al. COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. Nature 586, 594–599 (2020).
  6. Jackson LA, Anderson EJ, Rouphael NG, et al. An mRNA vaccine against SARS-CoV-2 — preliminary report. N Engl J Med. DOI: 10.1056/NEJMoa202
  7. Anderson EJ, Rouphael NG, Widge AT, Jackson LA, Roberts PC, Makhene M, Chappell JD, Denison MR, Stevens LJ, Pruijssers AJ, McDermott AB, Flach B, Lin BC, Doria-Rose NA, O'Dell S, Schmidt SD, Corbett KS, Swanson PA 2nd, Padilla M, Neuzil KM, Bennett H, Leav B, Makowski M, Albert J, Cross K, Edara VV, Floyd K, Suthar MS, Martinez DR, Baric R, Buchanan W, Luke CJ, Phadke VK, Rostad CA, Ledgerwood JE, Graham BS, Beigel JH; mRNA-1273 Study Group. Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults. N Engl J Med. 2020 Dec 17;383(25):2427-2438. doi: 10.1056/NEJMoa2028436. Epub 2020 Sep 29. PMID: 32991794; PMCID: PMC7556339.
  8. Folegatti PM, Ewer KJ, Aley PK. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet. 2020;396:467–478
  9. Ramasamy M, Minassian AM. Safety and immunogenicity of ChAdOx1 nCoV-19 (AZD1222) vaccine administered in a prime-boost regimen in older adults (COV002): a phase 2/3 single blind, randomised controlled trial. Lancet. 2020 doi: 10.1016/S0140-6736(20)32466-1. published online Nov 18