key: cord-0806074-gmxmckyf
authors: Priddy, F. H.; Williams, M.; Carson, S.; Lavender, B.; Mathieson, J.; Frampton, C.; Moreland, N. J.; McGregor, R.; Williams, G.; Brewerton, M.; Gell, K.; Ussher, J.; Le Gros, G.
title: Immunogenicity of BNT162b2 COVID-19 vaccine in New Zealand adults
date: 2022-04-06
journal: nan
DOI: 10.1101/2022.04.05.22273480
sha: ad529bb8b383518b8f4a5437e41294b34f243ca8
doc_id: 806074
cord_uid: gmxmckyf

Background: There is very little known about SARS-CoV-2 vaccine immune responses in New Zealand populations at greatest risk for serious COVID-19 disease. Methods: This prospective cohort study assessed immunogenicity in BNT162b2 mRNA vaccine recipients in New Zealand without previous COVID-19, with enrichment for M[a]ori, Pacific peoples, older adults [≥] 65 years of age, and those with co-morbidities. Serum samples were analysed at baseline and 28 days after second dose for presence of quantitative anti-S IgG by chemiluminescent microparticle immunoassay and for neutralizing capacity against Wuhan, Beta, Delta, and Omicron BA.1 strains using a surrogate viral neutralisation assay. Results: 285 adults with median age of 52 years were included. 55% were female, 30% M[a]ori, 28% Pacific peoples, and 26% [≥] 65 years of age. Obesity, cardiac and pulmonary disease and diabetes were more common than the general population. All participants received 2 doses of BNT162b2 vaccine. At 28 days after second vaccination, 99.6% had a sero-response to the vaccine, and anti-S IgG and neutralising antibody levels were high across gender and ethnic groups. IgG and neutralising responses declined with age. Lower responses were associated with age [≥]75 and diabetes, but not BMI. The ability to neutralise the Omicron BA.1 variant in vitro was severely diminished but maintained against other variants of concern. Conclusions: Vaccine antibody responses to BNT162b2 were generally robust and consistent with international data in this COVID-19 naive cohort with representation of key populations at risk for COVID-19 morbidity. Subsequent data on response to boosters, durability of responses and cellular immune responses should be assessed with attention to elderly adults and diabetics.

In 2019, a newly emergent coronavirus, Severe Acute Respiratory Syndrome coronavirus 2 45 (SARS-CoV-2) causing respiratory disease with potential for multi-system involvement 19) spread rapidly with significant morbidity, mortality and severe disruption of economic and 47 social patterns worldwide. In New Zealand, early and stringent border control and a nationwide 48 elimination policy limited SARS-CoV-2 spread during 2020 and most of 2021. Overseas, adults 49 ≥65 years of age, elderly in aged care homes, those with co-morbidities such as cardiac and 50 respiratory disease, diabetes and obesity were shown to be at higher risk of COVID-19-associated 51 morbidity and mortality. This was mirrored in New Zealand, with Māori and Pacific peoples also 52 being demonstrated to be at higher risk [1] . In March 2021, the BNT162b2 COVID-19 vaccine 53 manufactured by Pfizer/BioNTech was offered to the New Zealand population. Little data on 54 immunogenicity of COVID-19 vaccines is available in New Zealand populations. This prospective 55 cohort study assessed immunogenicity in a subset of BNT162b2 recipients, with a focus on Māori, 56

Pacific peoples, older adults ≥ 65 years of age, and those with co-morbidities. 57 58 There are several reasons to evaluate immune responses in local populations. The pivotal efficacy 59 trials for COVID-19 vaccines enrolled minimal numbers of Pacific populations and did not include 60

Māori. While vaccines are generally believed to act similarly across populations, reduced 61 immunogenicity and effectiveness have been demonstrated for specific vaccines in the elderly due 62 to immune senescence, and populations in low-resource settings possibly due to increased immune 63 activation [2] . Māori and Pacific populations in New Zealand have disproportionate rates of 64 cardiac and pulmonary disease, diabetes and obesity which are likely to increase morbidity from 65 COVID-19. Modeling of COVID-19 cases during 2020 and early 2021 showed that Māori had 2.5 66 . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 6, 2022. Laboratories, Abbott Park USA). The assay is a chemiluminescent microparticle immunoassay for 163 the quantitative detection of IgG antibodies to the RBD of the spike (S) protein with sensitivity 164 and specificity of 99.37% and 99.55% respectively according to the manufacturers data. Assay 165 specificity was calculated locally as 100% using antenatal samples (n=100) in New Zealand [10] . 166

The cut-off value is 50 AU/mL. This assay has been calibrated by the manufacturer using the WHO 167 international standard for SARS-CoV-2. AU/mL results were converted into IU/mL using a 168 conversion factor supplied by the manufacturer. 169

Serum samples were analysed at University of Auckland using a SARS-CoV-2 Surrogate Virus 172 Neutralisation Test (sVNT) marketed as cPASS (GenScript, Singapore). This assay measures 173 neutralising antibodies by quantifying the antibodies that block binding of the SARS-CoV-2 174 receptor binding domain to the hACE-receptor. Specificity was previously determined to be 100% 175 using 413 local samples [11] . Sera was diluted 1:10 and the assay was performed following 176 published protocols [12, 13] . Samples were considered positive if percent inhibition was above 177 20% as previously defined. Pre-vaccine samples were initially assessed against the ancestral strain 178 to determine if any of the cohort had SARS-CoV-2 neutralising antibodies pre-vaccine indicative 179 . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted April 6, 2022. ; https://doi.org/10.1101/2022.04.05.22273480 doi: medRxiv preprint of prior infection. Post-vaccination samples were assessed against the ancestral strain as well as to 180 the Beta, Delta and Omicron BA.1 variants of concern (VoC). This assay has been calibrated using 181 the WHO international standard for SARS-CoV-2. Percent inhibition results were converted to 182 IU/mL titers using an online tool validated for the ancestral strain [14] . The conversion was not 183 performed for the VoCs. For analysis of ethnicity the NZ census category of European was used and includes NZ European 216 as well as other Europeans. The proportions of Māori and Pacific peoples were higher than the 217 general population according to the 2018 NZ census, 30.2% v. 16.2% for Māori, and 28.1% v. 218 6.6% for Pacific peoples ( Table 1 ). The European subgroup had a higher median age (62 years) 219 than Māori (49.5 years) or Pacific peoples (42.5 years). Overweight and obesity were highly 220 prevalent among the study population (84%) which was also characterized by relatively high 221 prevalence of other comorbidities associated with increased COVID-19 morbidity. After 222 controlling for age differences among ethnic subgroups, there were statistically significant 223 differences in the prevalence of overweight, obesity, cardiac disease, pulmonary disease and 224 . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 6, 2022. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 6, 2022. ; https://doi.org/10.1101/2022.04.05.22273480 doi: medRxiv preprint ≥55 years (p<0.001). Looking more closely at the ≥55 years of age group, GMTs did not differ 248 significantly between 55-64 years of age and 65-74 years of age groups but were significantly 249 lower in ≥75 years of age group (Table 3) . GMT vaccine is based (Figure 3 ). Neutralisation capacity against ancestral strain was consistently high, 268 with mean 94.2% inhibition (95% CI 93.7-94.6). Similar to binding antibody, neutralising 269 responses were robust and did not differ across gender, ethnicity or BMI groups, but were 270 . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 6, 2022. responses. Increased BMI has been associated with reduced immune response to other vaccines 300 but not consistently [15, 16] . Māori participants had high rates of pulmonary disease, primarily 301 asthma, which may contribute to higher hospitalisation rates from COVID-19, but were not 302 associated with reduced vaccine response. In contrast, Pacific participants were more likely to have 303 diabetes, which was associated with reduced antibody responses. assays are more readily comparable to the data in this study. Studies found very high 314 seroconversion rates after 2 doses of BNT162b2 across age groups, similar to our findings [18, 19] . 315

Anti-S IgG titers were typically in the 3-4 log10 range (1000-10,000 U/mL), similar to our findings. 316 . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 6, 2022. ; https://doi.org/10.1101/2022.04.05.22273480 doi: medRxiv preprint For example, a study in 483 primarily white and female healthcare workers with median age 41 in 317 the UK used the Abbott Anti-S IgG Quant II assay and found a median titer of 10,058 AU/mL 318 (95% CI 6408-15,582) in vaccinees without prior infection 1 month post-second dose of 319

BNT162b2 [18] . A community-based study of 605 BNT162b2 recipients in the UK with median 320 age of 60 used the Roche Anti-S IgG assay and found a median titer of 5311 U/mL (95% CI 3133- is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 6, 2022. ; https://doi.org/10.1101/2022.04.05.22273480 doi: medRxiv preprint the ongoing study will be assessed for VoC neutralisation after boosting, which has been shown 363 to improve neutralising titers against Omicron BA.1 [5] . Future VoC can similarly be assessed to 364 inform the level of protection in the NZ population going forward. Consistent with both 365 international and local data, neutralisation correlated well with IgG antibody responses in this 366 cohort [10, 26] . 367 368 This study has several limitations. It does not assess vaccine efficacy as there was little or no 369 transmission during the study period described here. Only short term data through 28 days after 2 370 doses for the BNT162b2 vaccine is included. Understanding the durability of immune responses 371 in this cohort, and response to booster doses will be important to assess the vaccination programme 372 and shape future policy. Cellular immune responses are likely to be critical for both durability and 373 breadth of COVID-19 vaccine-induced protection and are not included in the current study. 374

Comorbidities were assessed by medical history and did not distinguish the duration or severity of 375 disease, or whether the condition was treated/controlled. Cardiac and pulmonary comorbidities 376 were grouped according to COVID-19 categories and include several diseases with varying 377 pathology which may have diluted any potential associations with a single condition. This study 378 did not include severely immunocompromised populations. Use of a high throughput surrogate 379 viral neutralisation assay allowed rapid analysis for both ancestral and VoC responses, however 380 there is less published comparative neutralisation data with this assay. 381 382 Vaccine antibody responses to the BNT162b2 were generally robust and consistent with 383 international data in this COVID-19 naïve cohort with representation of key NZ and Pacific 384 populations at risk for COVID-19 morbidity. Subsequent data on response to boosters, durability 385 . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 6, 2022. ; https://doi.org/10.1101/2022.04.05.22273480 doi: medRxiv preprint of responses and cellular immune responses should be assessed with attention to elderly adults and 386

Author contributions 389 FP, JU and GLG were responsible for study concept. FP and BL were responsible for study 390 protocol. MW, SC, JM and GW were responsible for study conduct, data and sample collection. 391 BL and KG were responsible for study coordination and data management. NM and RM were 392 responsible for laboratory analysis. CF and BL were responsible for data analysis. FP, CF, BL 393 and MB wrote the report. All authors reviewed and provided input to the report. We would like to acknowledge the study participants and the study teams at both sites for their 407 commitment to the study, including Michelle Sampson Lead Clinical Coordinator Lakeland 408 . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 6, 2022. 

. CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 6, 2022. . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 6, 2022. ; https://doi.org/10.1101/2022.04.05.22273480 doi: medRxiv preprint . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted April 6, 2022. ; https://doi.org/10.1101/2022.04.05.22273480 doi: medRxiv preprint . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted April 6, 2022. ; https://doi.org/10.1101/2022.04.05.22273480 doi: medRxiv preprint . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted April 6, 2022. ; https://doi.org/10.1101/2022.04.05.22273480 doi: medRxiv preprint . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted April 6, 2022. ; https://doi.org/10.1101/2022.04.05.22273480 doi: medRxiv preprint

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