Single-dose mRNA vaccine effectiveness against SARS-CoV-2 in healthcare workers extending 16 weeks post-vaccination: a test-negative design from Quebec, Canada

Abstract Introduction In Canada, first and second doses of mRNA vaccines against SARS-CoV-2 were uniquely spaced 16 weeks apart, but the duration of single-dose protection remains uncertain. We estimated one- and two-dose mRNA vaccine effectiveness (VE) among healthcare workers (HCWs) in Quebec, Canada including protection against varying outcome severity, variants of concern (VOC), and the stability of single-dose protection out to 16 weeks post-vaccination. Methods A test-negative design compared vaccination among SARS-CoV-2 test-positive and weekly-matched (10:1), randomly-sampled, test-negative HCWs using linked surveillance and immunization databases. Vaccine status was defined by one dose ≥14 days or two doses ≥7 days before illness onset or specimen collection. Adjusted VE was estimated by conditional logistic regression. Results Primary analysis included 5,316 cases and 53,160 controls. Single-dose VE was 70% (95%CI: 68-73) against SARS-CoV-2 infection, 73% (95%CI: 71-75) against COVID-19 illness and 97% (95%CI: 92-99) against associated hospitalization. Two-dose VE was 86% (95%CI: 81-90) and 93% (95%CI: 89-95), respectively, with no associated hospitalizations. VE was higher for non-VOC than VOC (73% Alpha) among single-dose (77%, 95%CI: 73-81 versus 63%, 95%CI: 57-67) but not two-dose recipients (87%, 95%CI: 57-96 versus 94%, 95%CI: 89-96). Across 16 weeks, no decline in single-dose VE was observed with appropriate stratification based upon prioritized vaccination determined by higher versus lower likelihood of direct patient contact. Conclusion One mRNA vaccine dose provided substantial and sustained protection to HCWs extending at least four months post-vaccination. In circumstances of vaccine shortage, delaying the second dose may be a pertinent public health strategy to consider.

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Single-dose mRNA vaccine effectiveness against SARS-CoV-2 in healthcare workers extending 16 weeks post-vaccination: a test-negative design from Quebec, Canada

10.1101/2021.07.19.21260445 ◽

2021 ◽

Author(s):

Sara Carazo ◽

Denis Talbot ◽

Nicole Boulianne ◽

Marc Brisson ◽

Rodica Gilca ◽

...

Keyword(s):

Single Dose ◽

Healthcare Workers ◽

Conditional Logistic Regression ◽

Vaccine Dose ◽

Vaccine Effectiveness ◽

Primary Analysis ◽

Post Vaccination ◽

Illness Onset ◽

Outcome Severity ◽

Specimen Collection

Introduction: In Canada, first and second doses of mRNA vaccines against SARS-CoV-2 were uniquely spaced 16 weeks apart, but the duration of single-dose protection remains uncertain. We estimated one- and two-dose mRNA vaccine effectiveness (VE) among healthcare workers (HCWs) in Quebec, Canada including protection against varying outcome severity, variants of concern (VOC), and the stability of single-dose protection out to 16 weeks post-vaccination. Methods: A test-negative design compared vaccination among SARS-CoV-2 test-positive and weekly-matched (10:1), randomly-sampled, test-negative HCWs using linked surveillance and immunization databases. Vaccine status was defined by one dose ≥14 days or two doses ≥7 days before illness onset or specimen collection. Adjusted VE was estimated by conditional logistic regression. Results: Primary analysis included 5,316 cases and 53,160 controls. Single-dose VE was 70% (95%CI: 68-73) against SARS-CoV-2 infection, 73% (95%CI: 71-75) against COVID-19 illness and 97% (95%CI: 92-99) against associated hospitalization. Two-dose VE was 86% (95%CI: 81-90) and 93% (95%CI: 89-95), respectively, with no associated hospitalizations. VE was higher for non-VOC than VOC (73% Alpha) among single-dose (77%, 95%CI: 73-81 versus 63%, 95%CI: 57-67) but not two-dose recipients (87%, 95%CI: 57-96 versus 94%, 95%CI: 89-96). Across 16 weeks, no decline in single-dose VE was observed with appropriate stratification based upon prioritized vaccination determined by higher versus lower likelihood of direct patient contact. Conclusion: One mRNA vaccine dose provided substantial and sustained protection to HCWs extending at least four months post-vaccination. In circumstances of vaccine shortage, delaying the second dose may be a pertinent public health strategy to consider.

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Single-dose mRNA vaccine effectiveness against SARS-CoV-2, including P.1 and B.1.1.7 variants: a test-negative design in adults 70 years and older in British Columbia, Canada

10.1101/2021.06.07.21258332 ◽

2021 ◽

Author(s):

Danuta M Skowronski ◽

Solmaz Setayeshgar ◽

Macy Zou ◽

Natalie Prystajecky ◽

John R Tyson ◽

...

Keyword(s):

British Columbia ◽

Single Dose ◽

Vaccine Effectiveness ◽

Community Dwelling ◽

Rt Pcr ◽

Vaccine Protection ◽

Post Vaccination ◽

Randomized Controlled ◽

Specimen Collection ◽

Negative Controls

Introduction: Randomized-controlled trials of mRNA vaccine protection against SARS-CoV-2 included relatively few elderly participants. We assess singe-dose mRNA vaccine effectiveness (VE) in adults ≥70-years-old in British Columbia (BC), Canada where the second dose was deferred by up to 16 weeks and where a spring 2021 wave uniquely included co-dominant circulation of B.1.1.7 and P.1 variants of concern (VOC). Methods: Analyses included community-dwelling adults ≥70-years-old with specimen collection between April 4 (epidemiological week 14) and May 1 (week 17). Adjusted VE was estimated by test-negative design through provincial laboratory and immunization data linkage. Cases were RT-PCR test-positive for SARS-CoV-2 and controls were test-negative. Vaccine status was defined by receipt of a single-dose ≥21 days before specimen collection, but a range of intervals was assessed. In variant-specific analyses, test-positive cases were restricted to those genetically-characterized as B.1.1.7, P.1 or non-VOC. Results: VE analyses included 16,993 specimens: 1,226 (7.2%) test-positive cases and 15,767 test-negative controls. Of 1,131 (92%) viruses genetically categorized, 509 (45%), 314 (28%) and 276 (24%) were B.1.1.7, P.1 and non-VOC lineages, respectively. VE was negligible at 14% (95% CI 0-26) during the period 0-13 days post-vaccination but increased from 43% (95% CI 30-53) at 14-20 days to 75% (95% CI 63-83) at 35-41 days post-vaccination. VE at ≥21 days was 65% (95% CI 58-71) overall: 72% (95% CI 58-81), 67% (95% CI 57-75) and 61% (95% CI 45-72) for non-VOC, B.1.1.7 and P.1, respectively. Conclusions: A single dose of mRNA vaccine reduced the risk of SARS-CoV-2 in adults ≥70-years-old by about two-thirds, with protection only minimally reduced against B.1.1.7 and P.1 variants. Substantial single-dose protection in older adults reinforces the option to defer the second dose when vaccine supply is scarce and broader first-dose coverage is needed.

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681Influenza vaccine effectiveness in young Japanese children over five seasons

International Journal of Epidemiology ◽

10.1093/ije/dyab168.209 ◽

2021 ◽

Vol 50 (Supplement_1) ◽

Author(s):

Wakaba Fukushima ◽

Saeko Morikawa ◽

Masashi Fujioka ◽

Tohru Matsushita ◽

Megumi Kubota ◽

...

Keyword(s):

Young Children ◽

Conditional Logistic Regression ◽

Vaccine Effectiveness ◽

Care Seeking ◽

Japanese Children ◽

Illness Onset ◽

Logistic Regression Models ◽

Care Seeking Behavior ◽

Seeking Behavior ◽

Health Care Seeking Behavior

Abstract Background Evidence is limited for influenza vaccine effectiveness (VE) against laboratory-confirmed influenza among young children. Using test-negative design (a modified case-control study) which minimizes confounding by health care-seeking behavior and misclassification of diseases, we aimed to monitor influenza VE among young children in Japan where all approved influenza vaccines are egg-propagated, inactivated formulations (IIV). Methods For seasons spanning 2013-14 to 2017-18 in Osaka and Fukuoka Prefectures, Japan, we employed prospective, active, and systematic recruitment of children aged <6 years who visited collaborating pediatric clinics within 7 days of influenza-like illness onset. Nasal aspirates were tested for influenza by real-time RT-PCR. Date of vaccination was confirmed by medical records or maternal and child health handbooks. Cases and controls were defined as being PCR-positive and -negative, respectively. Conditional logistic regression models were used to calculate adjusted VE ([1 - adjusted odds ratio] × 100%). Results We analyzed 4,614 subjects including 1,917 cases. VEs of IIV with 2 doses approximated 50%, ranging from 41% (95% confidence interval [CI]: 14 % to 60%) in 2016-17 season to 63% (95% CI: 45% to 76%) in 2017-18 season. Significant VEs were also shown for predominant circulating strains every season, irrespective of their antigenic match to vaccine strains (56% and 65% for A[H1N1]pdm, 37% and 50% for A[H3N2], and 60% for B[Yamagata]). Conclusions IIV provided modest and significant protection against laboratory-confirmed influenza in young Japanese children. Key messages Test-negative design is useful for monitoring influenza VE.

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Antibody Response to Live Attenuated Vaccines in Adults in Japan

Open Medicine ◽

10.1515/med-2016-0085 ◽

2016 ◽

Vol 11 (1) ◽

pp. 482-488 ◽

Cited By ~ 2

Author(s):

Taku Ogawa ◽

Fukumi Uchiyama-Nakamura ◽

Aiko Sugata-Tsubaki ◽

Yutaka Yamada ◽

Kenji Uno ◽

...

Keyword(s):

Single Dose ◽

Antibody Titer ◽

Healthcare Workers ◽

Adverse Reactions ◽

Varicella Vaccine ◽

Limited Sample ◽

Live Attenuated Vaccine ◽

Post Vaccination ◽

Vaccination Response ◽

Severe Adverse Reactions

AbstractThe purpose of this study was to examine the efficacy rendered with a single dose of live attenuated measles, rubella, mumps, and varicella containing vaccine.We inoculated healthcare workers (HCWs) with a single dose of vaccine to a disease lacking in antibody titer for those not meeting the criteria of our hospital (measles: <16.0 (IgG enzyme immunoassay (EIA)), rubella: ≤1:32 (hemagglutination-inhibition), mumps: <4.0 (IgG EIA), and varicella: <4.0 (IgG EIA)). At 28–60 days after vaccination, the antibody titer was tested again.We included 48 HCWs. A total of 32, 15, 31, and 10 individuals were inoculated with a single dose of measles-containing, rubella-containing, mumps, or varicella vaccine, respectively, and showed significant antibody elevation (9.2 ± 12.3 to 27.6 ± 215.6, p<0.001; 8 ± 1.2 to 32 ± 65.5, p<0.001; 3.0 ± 1.0 to 13.1 ± 8.6, p<0.05; and 2.6 ± 1.3 to 11.8 ± 8.1, p<0.001, respectively). Major side effects were not observed.In a limited population, a single dose of live attenuated vaccine showed elevation of antibody titer without any severe adverse reactions. However, whether the post-vaccination response rate criteria of our university was fulfilled could not be determined owing to limited sample size.

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Comparative single-dose mRNA and ChAdOx1 vaccine effectiveness against SARS-CoV-2, including early variants of concern: a test-negative design, British Columbia, Canada

10.1101/2021.09.20.21263875 ◽

2021 ◽

Author(s):

Danuta M Skowronski ◽

Solmaz Setayeshgar ◽

Macy Zou ◽

Natalie Prystajecky ◽

John R Tyson ◽

...

Keyword(s):

British Columbia ◽

Single Dose ◽

Genetic Characterization ◽

Infection Risk ◽

Vaccine Effectiveness ◽

Rt Pcr ◽

Randomized Controlled ◽

Specimen Collection ◽

Dose Vaccine

Introduction: In randomized controlled trials, single-dose efficacy against SARS-CoV-2 illness exceeded 90% for mRNA vaccines (BNT162b2 and mRNA-1273), and 75% for ChAdOx1. In British Columbia (BC), Canada second doses were deferred up to 16 weeks and ChAdOx1 was only initially recommended for adults 55 years of age and older. We compared single-dose vaccine effectiveness (VE) during the spring 2021 wave in BC when Alpha and Gamma variants of concern (VOC) predominated. Methods: VE was estimated against infection and hospitalization by test-negative design: cases were RT-PCR test-positive for SARS-CoV-2 and controls were test-negative. Adults 50-69 years old with specimen collection between April 4 and May 22 (weeks 14-20) were included. Variant-specific VE was estimated between weeks 17-20 when genetic characterization of all case viruses was performed, primarily through whole genome sequencing. Results: VE analyses included 7,116 (10%) cases and 60,958 controls. Three-quarters of vaccinated participants received mRNA vaccine (60% BNT162b2, 15% mRNA-1273) and 25% received ChAdOx1. Half of genetically characterized viruses were Alpha, with 38% Gamma, 4% Delta and 8% non-VOCs. Single-dose VE against any infection was 75% (95%CI: 72-78) for BNT162b2, 82% (95%CI: 76-87) for mRNA-1273 and 61% (95%CI: 54-66) for ChAdOx1. VE against hospitalization was 83% (95%CI: 76-89), 85% (95%CI: 63-94) and 96% (95%CI: 86-99), respectively. VE against Alpha vs. Gamma infections did not differ among mRNA (78%;95%CI: 73-82 and 80%;95%CI: 74-85) or ChAdOx1 (66%;95%CI: 57-74 and 60%;95%CI: 48-69) recipients. Conclusions: A single dose of mRNA vaccine reduced the SARS-CoV-2 infection risk by at least 75%, including infections due to early VOC. Although effectiveness of a single dose of ChAdOx1 was lower at 60% against infection, just one dose of any vaccine reduced the hospitalization risk by more than 80%. In the context of constrained vaccine supplies, these findings have implications for global vaccine deployment to reduce the overall burden of infections and hospitalizations due to SARS-CoV-2.

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Estimates of Single Dose and Full Dose BNT162b2 Vaccine Effectiveness among USAF Academy cadets, 1 Mar - 1 May 2021

10.1101/2021.07.28.21261138 ◽

2021 ◽

Author(s):

Douglas P Wickert ◽

Erin Almand ◽

Christopher A Cullenbine ◽

Odaro J Huckstep ◽

Joseph Rohrer ◽

...

Keyword(s):

Young Adults ◽

Single Dose ◽

Confidence Interval ◽

Military Training ◽

Vaccine Dose ◽

Infection Risk ◽

Vaccine Effectiveness ◽

Training Environment ◽

Fold Reduction ◽

University Setting

Beginning in early March 2021 and continuing through May 2021, the USAF Academy began vaccinating cadets for protection against the SARS-CoV-2 virus with the BNT162b2 (Pfizer-BioNTech) mRNA vaccine. During this period, vaccination of the almost 4200 cadet population increased from 3% to 85% and prevalence of COVID-19 in the cadet population was constant at approximately 0.4% as indicated by weekly surveillance testing. In this study, vaccine effectiveness at preventing infection is estimated by comparing infection risk as a function of time since vaccination. A statistically significant four-fold reduction in infection risk was observed 14 days after the first vaccine dose and an eleven-fold reduction in infection risk was observed in fully vaccinated cadets. Overall, the Pfizer-BioNTech vaccine was 91% (95% confidence interval = 55-99%) effective at preventing infection in healthy young adults (17-26 years of age) in a university setting and military training environment.

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Impact of prior SARS-CoV-2 infection on post-vaccination SARS-CoV-2 spike IgG antibodies in a longitudinal cohort of healthcare workers

10.1101/2021.09.16.21263576 ◽

2021 ◽

Author(s):

Diana Zhong ◽

Shaoming Xiao ◽

Amanda K Debes ◽

Emily R Egbert ◽

Patrizio Caturegli ◽

...

Keyword(s):

Serum Sample ◽

Healthcare Workers ◽

Natural Infection ◽

Vaccine Dose ◽

Igg Antibodies ◽

Linear Regression Models ◽

Post Vaccination ◽

Longitudinal Cohort ◽

Vaccine Type ◽

Antibody Levels

Waning serum antibodies against SARS-CoV-2 have sparked discussions about long-term immunity and need for vaccine boosters. We examined SARS-CoV-2 spike IgG antibodies in a longitudinal cohort, comparing antibody decay in individuals who received an mRNA SARS-CoV-2 vaccine, with and without prior SARS-CoV-2 infection. We completed a longitudinal cohort of healthcare workers (HWs) between June 2020 and September 2021. HWs were included if they had a serum sample collected after SARS-CoV-2 infection and/or a serum sample collected ≥ 14 days after second dose of an mRNA SARS-CoV-2 vaccine. Linear regression models adjusting for vaccine type, age, and sex were used to compare post-vaccination antibody levels between 1) HWs with and without prior SARS-CoV-2 infection and 2) HWs with prior SARS-CoV-2 infection ≤ 90 days and > 90 days prior to first vaccine. Serum was collected from 98 HWs after SARS-CoV-2 infection and before vaccine, and 1960 HWs ≥ 14 days following second vaccine dose. Serum spike antibody levels were higher after vaccination than after natural infection. Compared to SARS-CoV-2 naïve individuals, those with prior infection maintained higher post-vaccination mean spike IgG values at 1, 3, and 6 months, after adjusting for age, sex, and vaccine type. Individuals with PCR-confirmed infection > 90 days before vaccination had higher post-vaccination antibody levels than individuals infected ≤ 90 days before vaccination. Individuals with three exposures to spike protein maintain the highest antibody levels particularly when first and second exposures were greater than 90 days apart. A booster dose provides a third exposure and may similarly induce a more durable antibody response.

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Comprehensive assessment of humoral response after Pfizer BNT162b2 mRNA Covid-19 vaccination: a three-case series

10.1101/2021.03.19.21253989 ◽

2021 ◽

Author(s):

Elisa Danese ◽

Martina Montagnana ◽

Gian Luca Salvagno ◽

Matteo Gelati ◽

Denise Peserico ◽

...

Keyword(s):

Immune Response ◽

Neutralizing Antibodies ◽

Healthcare Workers ◽

Protein Concentration ◽

Venous Blood ◽

Case Series ◽

Vaccine Dose ◽

Humoral Response ◽

Post Vaccination ◽

Humoral Immune

Background. Since universal vaccination is a pillar against coronavirus disease 2019 (COVID-19), monitoring anti-SARS-CoV-2 neutralizing antibodies is essential for deciphering post-vaccination immune response. Methods. Three healthcare workers received 30 μg BNT162b2 mRNA Covid-19 Vaccine, followed by a second identical dose, 21 days afterwards. Venous blood was drawn at baseline and at serial intervals, up to 63 days afterwards, for assessing total immunoglobulins (Ig) anti-RBD (receptor binding domain), IgG anti-S1/S2, IgG anti-RBD, IgM anti-RBD, IgM anti-N/S1 and IgA anti-S1. Results. All subjects were SARS-CoV-2 seronegative at baseline. Total Ig anti-RBD, IgG anti-S1/S2 and IgG anti-RBD levels increased between 91-368 folds until 21 days after the first vaccine dose, then reached a plateau. The levels raised further after the second dose (by ~30-, ~8- and ~8-fold, respectively), peaking at day 35, but then slightly declining and stabilizing ~50 days after the first dose. IgA anti-S1 levels increased between 7-11 days after the first dose, slightly declined before the second dose, after which levels augmented by ~24-fold from baseline. The anti-RBD and anti-N/S1 IgM kinetics were similar to that of anti-S1 IgA, though displaying substantially weaker increases and modest peaks, only 4 to 7-fold higher than baseline. Highly significant inter-correlation was noted between total Ig anti-RBD, anti-S1/S2 and anti-RBD IgG (all r=0.99), whilst other anti-SARS-CoV-2 antibodies displayed lower, though still significant, correlations. Serum spike protein concentration was undetectable at all time points. Conclusions. BNT162b2 mRNA vaccination generates a robust humoral immune response, especially involving IgG and IgA, magnified by the second vaccine dose.

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Effectiveness of mRNA-1273 against delta, mu, and other emerging variants of SARS-CoV-2: test negative case-control study

BMJ ◽

10.1136/bmj-2021-068848 ◽

2021 ◽

pp. e068848

Author(s):

Katia J Bruxvoort ◽

Lina S Sy ◽

Lei Qian ◽

Bradley K Ackerson ◽

Yi Luo ◽

...

Keyword(s):

Hospital Admission ◽

Case Control Study ◽

Conditional Logistic Regression ◽

Case Control ◽

Vaccine Effectiveness ◽

Specimen Collection ◽

Negative Case ◽

Delta Infection ◽

Control Study ◽

Dose Vaccine

Abstract Objectives To evaluate the effectiveness of the mRNA-1273 vaccine against SARS-CoV-2 variants and assess its effectiveness against the delta variant by time since vaccination. Design Test negative case-control study. Setting Kaiser Permanente Southern California (KPSC), an integrated healthcare system. Participants Adult KPSC members with a SARS-CoV-2 positive test sent for whole genome sequencing or a negative test from 1 March 2021 to 27 July 2021. Interventions Two dose or one dose vaccination with mRNA-1273 (Moderna covid-19 vaccine) ≥14 days before specimen collection versus no covid-19 vaccination. Main outcome measures Outcomes included infection with SARS-CoV-2 and hospital admission with covid-19. In pre-specified analyses for each variant type, test positive cases were matched 1:5 to test negative controls on age, sex, race/ethnicity, and specimen collection date. Conditional logistic regression was used to compare odds of vaccination among cases versus controls, with adjustment for confounders. Vaccine effectiveness was calculated as (1–odds ratio)×100%. Results The study included 8153 cases and their matched controls. Two dose vaccine effectiveness was 86.7% (95% confidence interval 84.3% to 88.7%) against infection with the delta variant, 98.4% (96.9% to 99.1%) against alpha, 90.4% (73.9% to 96.5%) against mu, 96-98% against other identified variants, and 79.9% (76.9% to 82.5%) against unidentified variants (that is, specimens that failed sequencing). Vaccine effectiveness against hospital admission with the delta variant was 97.5% (92.7% to 99.2%). Vaccine effectiveness against infection with the delta variant declined from 94.1% (90.5% to 96.3%) 14-60 days after vaccination to 80.0% (70.2% to 86.6%) 151-180 days after vaccination. Waning was less pronounced for non-delta variants. Vaccine effectiveness against delta infection was lower among people aged ≥65 years (75.2%, 59.6% to 84.8%) than those aged 18-64 years (87.9%, 85.5% to 89.9%). One dose vaccine effectiveness was 77.0% (60.7% to 86.5%) against infection with delta. Conclusions Two doses of mRNA-1273 were highly effective against all SARS-CoV-2 variants, especially against hospital admission with covid-19. However, vaccine effectiveness against infection with the delta variant moderately declined with increasing time since vaccination.

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Hepatitis B revaccination for healthcare workers who are anti-HBs-negative after receiving a primary vaccination series

Revista da Sociedade Brasileira de Medicina Tropical ◽

10.1590/s0037-86822012000500018 ◽

2012 ◽

Vol 45 (5) ◽

pp. 639-642 ◽

Cited By ~ 1

Author(s):

Marta Heloisa Lopes ◽

Ana Marli Christovam Sartori ◽

Tatiany Viviany Gonçalves Souza ◽

Melissa Mascheretti ◽

Tânia do Socorro Souza Chaves

Keyword(s):

Hepatitis B ◽

Surface Antigen ◽

Healthcare Workers ◽

Vaccine Dose ◽

Primary Vaccination ◽

Practical Approach ◽

Post Vaccination ◽

Hb Vaccine

INTRODUCTION: This study aimed to evaluate the response to hepatitis B (HB) revaccination of healthcare workers (HCW) who are negative for antibodies to HB surface antigen (anti-HBs) after a complete vaccination series. METHODS: HCW whose anti-HBs test was performed > 90 days after a HB vaccination course were given a 4th dose. A post-vaccination test was done within 30 to 90 days. RESULTS: One hundred and seventy HCW were enrolled: 126 (74.1%) were anti-HBs-positive after the 4th dose. CONCLUSIONS: Rechecking anti-HBs after the 4th HB vaccine dose is a practical approach in case of post-vaccination tests performed >90 days after the full vaccination course.

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