key: cord-0315135-kxv4rs4u
authors: Mahasirimongkol, S.; Khunphon, A.; Kwangsukstid, O.; Sapsutthipas, S.; Wichaidit, M.; Rojanawiwat, A.; Wichuckchinda, N.; Puangtubtim, W.; Pimpapai, W.; Soonthorncharttrawat, S.; Wanitchang, A.; Jongkaewwattana, A.; Srisutthisamphan, K.; Phainupong, D.; Thawong, P.; Piboonsiri, P.; Sawaengdee, W.; Somporn, T.; Ritthitham, K.; Phumiamorn, S.; Pinyosukhee, N.; Wichajarn, R.; Dhepaksorn, P.; Iamsiritahworn, S.
title: Immunogenicity and adverse events of priming with inactivated whole SARS-CoV-2 vaccine (CoronaVac) followed by boosting the ChAdOx1 nCoV-19 vaccine
date: 2021-11-08
journal: nan
DOI: 10.1101/2021.11.05.21264700
sha: 97b1a3d1661804fde24aeeaa2431312ddc667e66
doc_id: 315135
cord_uid: kxv4rs4u

Background: Responding to SARS-CoV-2 Delta variants escaped the vaccine-induced immunity and waning immunity from the inactivated whole virus vaccine, Thailand recently proposed a heterologous inactivated whole virus vaccine (CoronaVac) viral vector vaccine (ChAdOx1 nCoV-19) prime-boost vaccine regimen(I/V). This study aims to evaluate the immunogenicity and adverse events of this regimen by comparison with homologous CoronaVac, ChAdOx1 nCoV-19, and convalescent serum. Method: Immunogenicity was evaluated by the level of IgG antibodies against the receptor-binding domain of the SARS-CoV-2 spike protein (S1 subunit) (anti-S RBD). At 2 weeks following the second dosage, a selection of random samples was tested for plaque reduction neutralisation (PRNT) and Pseudotype-Based Microneutralization test (PVNT) against SARS-CoV-2 variants of concern (VOCs). The safety profile of heterologous CoronaVac-ChAdOx1 nCoV-19 prime-boost vaccine regimen was described by interviewing at the 1-month visit. Result: Between April to August 2021,426 participants were included in the study, with 155 obtaining CoronaVac-ChAdOx1 nCoV-19(I/V),32 obtaining homologous CoronaVac(I/I),47 obtaining homologous ChAdOx1 nCoV-19(V/V),169 with history covid-19 infection. Geometric mean titers (GMTs) of anti-S RBD level in the I/V group compare 2wks and 4 wks ( 873.9 vs 639,p=0.00114).At 4 wks, GMTs of anti-S RBD level in I/V group was 639, 95% CI 63-726,and natural infection group 177.3, 95% CI 42-221, and V/V group 211.1, 95% CI 77-152 ,and I/I group 108.2 ,95% CI 77-152 ; all p<0.001).At 2 wks, The GMTs of 50%PRNT of 19 sampling from the I/V group is 434.5, 95% CI 326-579, against wild type and 80.4, 95% CI 56-115, against alpha and 67.4, 95% CI 48-95, against delta and 19.8, 95% CI 14-30, against beta; all p<0.001. At 2 wks, The GMTs of 50%PVNT of 15 sampling from the I/V group is 597.8, 95% CI 368-970, against wild type and 163.9, 95% CI 89-301, against alpha and 157.7, 95% CI 66-378, against delta. The AEs in the I/V schedule were well tolerated and generally unremarkable. Conclusion: The I/V vaccination is a mixed regimen that induced higher immunogenicity and shall be considered for responding to Delta Variants when only inactivated whole virus vaccine and viral vector vaccine was available.

perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted November 8, 2021. ; https://doi.org/10.1101/2021.11.05.21264700 doi: medRxiv preprint 6 reported deaths due to its higher transmissibility, more severe and vaccine perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted November 8, 2021. ; https://doi.org/10.1101/2021.11.05.21264700 doi: medRxiv preprint 9 recommendation to I/V vaccination from the national vaccination academic 175 subcommittee. The benefit of this I/V regimen was an opportunity to achieve 176 higher immunogenicity than I/I regimens and in shorter duration intervals when 177 compared to the V/V regimen, the risk was the possibility of a higher rate of 178 adverse events than the I/I schedule.

The benefit and risks of second vaccination with ChAdOx1 nCoV-19 were perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in Quant assay with Abbott internal reference calibrators, the correlation between 216 All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted November 8, 2021. ; https://doi.org/10.1101/2021.11.05.21264700 doi: medRxiv preprint relationships of the AU/mL unit to the WHO (BAU/mL unit is at 0.142 × 217 AU/mL) with the 0.999 correlation coefficient. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted November 8, 2021. ; https://doi.org/10.1101/2021.11.05.21264700 doi: medRxiv preprint incubation in a humidified cell-culture incubator for 48 h at 37 °C in 5% CO 2 .

To measure luminescence activity, equal volumes of Bright- perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in Sigma Aldrich, USA, with 1% of 10,000 units/ml Penicillin-10,000 ug/ml 262 Streptomycin (Sigma, USA) and 10% FBS) were replaced after removing 263 excessive viruses. All plates were incubated at 37OC, 5% CO2 for 7 days. Cells 

The Demographic data between vaccination groups were described in Table 1 . perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted November 8, 2021. ; https://doi.org/10.1101/2021.11.05.21264700 doi: medRxiv preprint COVID19 breakthrough infection following immunization 345 During a telephone interview, two participants reported to the investigator that 346 they couldn't attend the 4 wks visit for blood samples collection due to their 347 COVID19 situation that they experienced during the third week after the I/V The PRNT 50 of 19 samples from the I/V schedule was analyzed and reported in Beta variants was achieved in 63% of these samples. In 19 participants from the 364 I/V group were evaluated for their neutralizing antibody (Nab) by PRNT 50 for 365 All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in (Figure 7) .

In addition, all participants (n=19/19) had PRNT 50 titers ≥10 375 (Nab positivity cut-off) ≥10 (Nab positivity cut-off) against wild type, Alpha, and 376 Delta strains. Participants (n=12/19,63%) had PRNT 50 titers ≥10 against beta 377 variant (Table 9) . perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The adverse events (AEs) to the first vaccine dose with CoronaVac in this study 406 were described separately into two groups of samples. Group 1a was 30 407 All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted November 8, 2021. ; https://doi.org/10.1101/2021.11.05.21264700 doi: medRxiv preprint common local responses such as injection site pain (n=54,35.06%) and other 428 were described in Supplementary(Table4). perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The Nab is highest to wild type variant, then to Alpha variant followed 455 by delta variant, and the least Nab to Beta variant. This is consistent with a 456 study that analyzed neutralization capacities by protein-based 206 ACE2 RBD 457 competition assay was highest in wild-type, followed by alpha, delta, and Beta, perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted November 8, 2021. ; https://doi.org/10.1101/2021.11.05.21264700 doi: medRxiv preprint the types and timing of vaccine should be determined as the follow-up study 533 from this cohort of vaccine recipients for providing a further recommendation.

There are several limitations to our research. First, our study did not 535 collect comparison data on immunity levels at baseline before the study and perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted November 8, 2021. ; https://doi.org/10.1101/2021.11.05.21264700 doi: medRxiv preprint 27 immunization. The I/V vaccination is a mixed regimen that induced higher 555 immunogenicity with a shorter duration to peak immunogenicity compared to 556 the I/I schedule. In a situation where the viral vector vaccine is inadequate, we 557 should consider this vaccine schedule for responding to Delta Variants. We 558 propose that this initial assessment encourage future research of heterologous 559 prime-boost vaccination regimens for COVID-19. We would like to express our gratitude to the whole COVID-19 research team 573 including all of the study participants. We thank Dr. Mark Simmerman for his 574 critical data and recommendations. 575 All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in 

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preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted

All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted November 8, 2021. ; https://doi.org/10.1101/2021.11.05.21264700 doi: medRxiv preprint