Vaccines for 5-11 year olds: FDA meeting cliff notes
Today VRBPAC (an external scientific advisory committee to the FDA) voted in favor of the Pfizer COVID19 vaccine for 5-11 year olds. VRBPAC was the second stop in a long process to get the vaccine authorized for emergency use. This was a much anticipated meeting for two reasons:
Background While Coronavirus disease 2019 (Covid-19) vaccines are highly effective, breakthrough infections are occurring. Booster vaccinations have recently received emergency use authorization (EUA) for certain populations but are restricted to homologous mRNA vaccines. We evaluated homologous and heterologous booster vaccination in persons who had received an EUA Covid-19 vaccine regimen.
Methods In this phase 1/2 open-label clinical trial conducted at ten U.S. sites, adults who received one of three EUA Covid-19 vaccines at least 12 weeks prior to enrollment and had no reported history of SARS-CoV-2 infection received a booster injection with one of three vaccines (Moderna mRNA-1273 100-μg, Janssen Ad26.COV2.S 5×1010 virus particles, or Pfizer-BioNTech BNT162b2 30-μg; nine combinations). The primary outcomes were safety, reactogenicity, and humoral immunogenicity on study days 15 and 29.
Results 458 individuals were enrolled: 154 received mRNA-1273, 150 received Ad26.CoV2.S, and 153 received BNT162b2 booster vaccines. Reactogenicity was similar to that reported for the primary series. Injection site pain, malaise, headache, and myalgia occurred in more than half the participants. Booster vaccines increased the neutralizing activity against a D614G pseudovirus (4.2-76-fold) and binding antibody titers (4.6-56-fold) for all combinations; homologous boost increased neutralizing antibody titers 4.2-20-fold whereas heterologous boost increased titers 6.2-76-fold. Day 15 neutralizing and binding antibody titers varied by 28.7-fold and 20.9-fold, respectively, across the nine prime-boost combinations.
Conclusion Homologous and heterologous booster vaccinations were well-tolerated and immunogenic in adults who completed a primary Covid-19 vaccine regimen at least 12 weeks earlier.
(Funded by National Institute of Allergy and Infectious Diseases; [Clinical Trials.gov][1] number, [NCT04889209][2])
### Competing Interest Statement
RLA, HME, RER, MB, TMB, ACK, DD, CMP, JLA, ABD, SEO, SC, SUN, DS, JZ, CPDI, ERB, MJM, and AE report no competing interests. KEL receives grant awards from the National Institute of Allergy and Infectious Disease (NIAID), and funding from Pfizer Inc COVID-19 vaccine research. LAJ's institution receives grant funding from NIH and CDC for vaccine-related assessments, including those of COVID-19 vaccines. ARB has grant funding from Pfizer, Janssen, Merck and Cyanvac for non-Covid-related work and servesa as a consultant for GSK and Janssen. CAR's institution has received funds to conduct clinical research from the National Institutes of Health, CDC, BioFire Inc, Genentech, GSK, Janssen, MedImmune, Merck, Micron, Moderna, Novavax, PaxVax, Pfizer, Regeneron, Sanofi-Pasteur. She is co-inventor of patented RSV vaccine technology, which has been licensed to Meissa Vaccines, Inc. JMM has served as a consultant for Merck, Sharp and Dohme for non-Covid-related work. CJ receives funding from the Bill and Melinda Gates Foundation, NIH and CDC, consults for Gilead and Abbvie, serves on a DSMB for MedPace, and receives royalties from UpToDate. MJM has laboratory research and clinical trials contracts for vaccines or MAB vs SARS-CoV-2 with Lilly, Pfizer (exclusive of the current work), and Sanofi; personal fees for Scientific Advisory Board service from Merck, Meissa Vaccines, Inc. and Pfizer RCB receives funding for vaccine trials from Path Nipah and Pfizer. RWF receives funding to perform clinical trials from Pfizer, Moderna, Astra Zeneca and Emergent Health, and he serves on advisory boards for Johnson & Johnson, Merck, Sanofi Pasteur and Seqirus. SE receives funding to her institution from Sanofi Pasteur for a non-Dovid vaccine study. MSS is on the Advisory Board of Moderna DCM receives funding from NIH and Moderna for laboratory studies of COVID-19 vaccine antibody responses. KMN holds a grant from Pfizer, without salary support, for a COVID-19 vaccine study, and salary support from the National Institutes of Health (NIH) for work on multiple COVID-19 vaccine trials DSS is supported by grant awards from NIH/NIAID. PCR and JHB report a pending U.S. Patent Application No. 63/025,918 entitled Coronavirus RNA vaccines and methods of use
### Clinical Trial
NCT04889209
### Funding Statement
The trial was sponsored and primarily funded by the Infectious Diseases Clinical Research Consortium through the National Institute for Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH), under award numbers UM1AI48372, UM1AI148373, UM1AI148450, UM1AI148452, UM1AI148573, UM1AI148574, UM1AI148575, UM1AI148576, UM1AI148684, UM1 AI148689 and with support from the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVICs) contract 75N93019C00050 and NIH Vaccine Research Center.
### Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
Advarra Center for IRB Intelligence
I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
Yes
I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.
Yes
All available data produced in the present work are contained in the manuscript
[1]: http://ClinicalTrials.gov
[2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04889209&atom=%2Fmedrxiv%2Fearly%2F2021%2F10%2F15%2F2021.10.10.21264827.atom
(2) Prof. Shane Crotty auf Twitter: "Is it good to mix COVID vaccines? This is a really great clinical study by Lyke et al., reported at the recent FDA meeting. Mix-and-match COVID vaccines https://t.co/emvY6ikgos" / Twitter
Is it good to mix COVID vaccines?
This is a really great clinical study by Lyke et al., reported at the recent FDA meeting.
Mix-and-match COVID vaccines
https://t.co/emvY6ikgos
A high attack rate of 90% of SARS-CoV-2 Delta variant infections in crew personnel on a single navy ship - PubMed
272 soldiers out of the 301 soldiers (90.4%) were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant of concern (VOC) on a single navy ship. This outbreak provides three lessons for the pandemic. This incident clearly demonstrates the transmission characteristic …
Detailed reconstruction of the Iranian COVID-19 epidemic reveals high attack rates of SARS-CoV-2 in several provinces
Since the first cases of COVID-19 were reported in Qom, Iran, almost 19 months ago, the transmission dynamics across the country and the health burden of COVID-19 has remained largely unknown due to the scarcity of epidemiological analyses and lack of provincial data on the number of COVID-19 cases and deaths. For the first time, we reconstruct the epidemic trajectory across the country and assess the level of under-reporting in infections and deaths using province-level age-stratified weekly all-cause mortality data. Our estimates suggest that as of 2021-09-17, only 48% (95% confidence interval 43-55%) of COVID-19 deaths in Iran have been reported. We find that in the most affected provinces such as Qazvin, Qom, and East Azerbaijan approximately 0.4% of the population have died of COVID-19 so far. We also find significant heterogeneity in the estimated attack rates across the country with 11 provinces reaching close to or higher than 100% attack rates. Despite a relatively young age structure in Iran, our analysis reveals that the infection fatality rate gradually increased over time in several provinces and reached levels that are comparable some of the high-income countries with a larger percentage of older adults, suggesting that limited access to medical services, coupled with undercounting of COVID-19-related deaths, can have a significant impact on COVID-19 fatalities. These results also show that despite several waves of infection and high attack rates in many provinces with largely unmitigated epidemics, herd immunity through natural infection has not been achieved.
### Competing Interest Statement
The authors have declared no competing interest.
### Funding Statement
MG is funded by the Biotechnology and Biological Science Research Council (BBSRC), grant number BB/M011224/1.
### Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
This work does not include any clinical trial or prospective interventional study data.
I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
Yes
I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.
Yes
All the data used for the analysis are available online on our GitHub repository (github.com/mg878/Iran\_WeeklyMortality). For regular updates on excess mortality in Iran, you can visit: https://github.com/akarlinsky/world\_mortality.
https://github.com/mg878/Iran_WeeklyMortality
Prevention of host-to-host transmission by SARS-CoV-2 vaccines - ScienceDirect
As the number of individuals vaccinated against SARS-CoV-2 rises worldwide, population-level data regarding the vaccines' ability to reduce infection …
Real-world data show filters clean SARS-CoV-2 from air
Research at a UK hospital suggests that portable filters effectively remove SARS-CoV-2 virus particles from the air — the first such evidence from a real-world setting (A. Conway-Morris et al. Preprint at medRxiv https://doi.org/gm3hkf; 2021).
Earlier experiments that tested air filters’ performance assessed their ability to remove inactive particles in carefully controlled environments. As a result, “what was not known was how effective they would be in a real-world ward setting for clearing SARS-CoV-2”, says study co-author Vilas Navapurkar, a physician at Addenbrooke’s Hospital in Cambridge, UK.
To determine how high-efficiency particulate air (HEPA) filters stand up to real-world conditions, Navapurkar and his co-authors installed them in two fully occupied COVID-19 wards. They collected air samples from the wards during a week when the filters were switched on and two weeks when they were off.
In one ward, the team found SARS-CoV-2 particles in the air when the filter was off, but not when it was on. And on both wards, the filters removed other pathogens, such as Staphylococcus aureus and Escherichia coli. The results, which have not been peer reviewed, indicate that HEPA filters might be an affordable way to reduce COVID-19 transmission in hospitals.
Nature Neuroscience - A novel study led by scientists in Lübeck, Germany, shows that SARS-CoV-2-infected brain endothelial cells undergo cell death due to the cleavage of NEMO by the viral...
Post COVID-19 in children, adolescents, and adults: results of a matched cohort study including more than 150,000 individuals with COVID-19
Background: Long-term health sequelae of the coronavirus disease 2019 (COVID-19) are a major public health concern. However, evidence on post-acute COVID-19 syndrome (post COVID-19) is still limited, particularly for children and adolescents. Utilizing comprehensive healthcare data on more than 45 percent of the German population from January 2019 through December 2020, we investigated post COVID-19 in children/adolescents and adults. Methods: From a total of 38 million individuals, we identified all patients with laboratory confirmed diagnosis of COVID-19 through June 30, 2020. A control cohort was assigned using 1:5 exact matching on age, sex, and propensity score matching on prevalent medical conditions. COVID-19 and control cohorts were followed for incident morbidity outcomes documented at least three months after the date of COVID-19 diagnosis, which was used as the index date for both groups. Overall, 96 pre-defined outcomes were aggregated into 13 diagnosis/symptom complexes and three domains (physical health, mental health, physical/mental overlap domain). We used Poisson regression to estimate incidence rate ratios (IRRs) with 95%-confidence intervals (95%-CI). Results: The study population included 157,134 individuals (11,950 children/adolescents and 145,184 adults) with confirmed COVID-19. COVID-19 and control cohort were well-balanced regarding covariates. For all health outcomes combined, incidence rates (IRs) in the COVID-19 cohort were significantly higher than those in the control cohort in both children/adolescents (IRR=1.30, 95%-CI=[1.25-1.35], IR COVID-19=436.91, IR Control=335.98) and adults (IRR=1.33, 95%-CI=[1.31-1.34], IR COVID-19=615.82, IR Control=464.15). The relative magnitude of increased documented morbidity was similar for the physical, mental, and physical/mental overlap domain. In the COVID-19 cohort, incidence rates were significantly higher in all 13 diagnosis/symptom complexes in adults and in ten diagnosis/symptom complexes in children/adolescents. IRR estimates were similar for the age groups 0-11 and 12-17. Incidence rates in children/adolescents were consistently lower than those in adults. Among the specific outcomes with the highest IRR and an incidence rate of at least 1/100 person-years in the COVID-19 cohort in children and adolescents were malaise/fatigue/exhaustion (IRR=2.28, 95%-CI=[1.71-3.06], IR COVID-19=12.58, IR Control=5.51), cough (IRR=1.74, 95%-CI=[1.48-2.04], IR COVID-19=36.56, IR Control=21.06), and throat/chest pain (IRR=1.72, 95%-CI=[1.39-2.12], IR COVID-19=20.01, IR Control=11.66). In adults, these included dysgeusia (IRR=6.69, 95%-CI=[5.88-7.60], IR COVID-19=12.42, IR Control=1.86), fever (IRR=3.33, 95%-CI=[3.01-3.68], IR COVID-19=11.53, IR Control=3.46), and dyspnea (IRR=2.88, 95%-CI=[2.74-3.02], IR COVID-19=43.91, IR Control=15.27). Conclusions: This large, matched cohort study indicates substantial new-onset post COVID-19 morbidity in pediatric and adult populations based on routine health care documentation. Further investigation is required to assess the persistence and long-term health impact of post COVID-19 conditions, especially in children and adolescents.
### Competing Interest Statement
AV, FT, JJ, JS, JW, MR, MS, and ON report institutional funding for parts of this project from the German BMBF. Unrelated to this study, FT reports payments for lectures from Dresden International University. JA reports grants from the Federal State of Saxony. Unrelated to this study, JS reports grants for investigator-initiated research from the German GBA, the BMG, BMBF, EU, Federal State of Saxony, Novartis, Sanofi, ALK, and Pfizer. He also participated in advisory board meetings for Sanofi, Lilly, and ALK. MB reports payment for data analysis which is presented in this paper from DAK‐Gesundheit. Unrelated to this study, MB reports grants from German GBA and Sanofi Pasteur and consulting fees from Janssen‐Cilag. He participated in an advisory board for GSK. NT is member of the Steering Committee of the German Society for Pediatric Infectious Diseases (DGPI) and is the DGPI-mandated person for the pediatric expert group on long-COVID in children and adolescents. SB is Head of Analytics and Data Science at AOK PLUS, Dresden, Germany. Unrelated to this study, STSCH reports payments for a guest lecture at TU Berlin. The other authors declare that they have no competing interest.
### Funding Statement
AV, FT, JJ, JS, JW, MR, MS, and ON report institutional funding for parts of this project from the German BMBF (grant number: 01KX2021).
### Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
The ethics committee of the TU Dresden approved this study (approval number: BO-EK (COVID)-482102021).
I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
Yes
I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.
Yes
Individual-level data are not publicly available due to legal and data protection restrictions. Aggregate statistics are available upon reasonable request to the authors.
Signal Transduction and Targeted Therapy - <ArticleTitle Language="En" xml:lang="en">SARS-CoV-2 crosses the blood–brain barrier...
(4) Jan Wenzel auf Twitter: "Our finding on #SARSCoV2 and the brain´s microvasculature was published in @NatureNeuro today. We used cells, animal models, and #COVID19 patients samples to show that the virus kills brain endothelial cells, possibly explaining neurological symptoms: https://t.co/ZV9SHqef8V." / Twitter
Our finding on #SARSCoV2 and the brain´s microvasculature was published in @NatureNeuro today. We used cells, animal models, and #COVID19 patients samples to show that the virus kills brain endothelial cells, possibly explaining neurological symptoms: https://t.co/ZV9SHqef8V.
Carsten Watzl auf Twitter: "(1) Nachdem ich mich heute bei der dpa zu Langzeitfolgen bei Impfungen geäußert habe, fühlen sich viele Menschen dazu berufen, mir per Email die 'Wahrheit' mitzuteilen. Daher hier mal ein 🧵 Spoiler: Vor Langzeitfolgen der COVID-19 Impfung muss man keine Angst haben!" / Twitter
(1) Nachdem ich mich heute bei der dpa zu Langzeitfolgen bei Impfungen geäußert habe, fühlen sich viele Menschen dazu berufen, mir per Email die 'Wahrheit' mitzuteilen. Daher hier mal ein 🧵
Spoiler: Vor Langzeitfolgen der COVID-19 Impfung muss man keine Angst haben!
Referent: Herr Prof. Dr. Michael Meyer-Hermann (Helmholtz-Zentrum für Infektionsforschung GmbH in Braunschweig)Thema: Die Rolle mathematischer Vorhersagen i...
Carsten Watzl auf Twitter: "Und die Wirksamkeit? Die Kinder machen auf die 10ug Impfung sogar noch etwas mehr Antikörper als die 12-18J auf die 30ug Impfung! Auch mehr neutralisierende Antikörper gegen Delta! https://t.co/OST94nR5Uk" / Twitter
Und die Wirksamkeit? Die Kinder machen auf die 10ug Impfung sogar noch etwas mehr Antikörper als die 12-18J auf die 30ug Impfung! Auch mehr neutralisierende Antikörper gegen Delta! https://t.co/OST94nR5Uk
Studies show mRNA COVID-19 vaccination does not hinder fertility
COVID-19 vaccination did not impair fertility, early pregnancy outcomes or sperm quality, according to findings from three studies presented at the American Society for Reproductive Medicine Scientific Congress & Expo.“We all know firsthand how the COVID-19 pandemic has changed the landscape of health care,” Devora Aharon, MD, a fellow in reproductive endocrinology and infertility
Eric Feigl-Ding auf Twitter: "BEST BOOSTER? Mix it up — but depends which you had first. Switching vaccine for the booster seems to be the best—Pfizer to Moderna booster, Moderna to Pfizer for booster, and J&J should switch to Moderna / Pfizer booster. HT to @ScientistSwanda. #COVID19 #BoosterShots #vaccinate https://t.co/Yw0R6atC7i" / Twitter
BEST BOOSTER? Mix it up — but depends which you had first. Switching vaccine for the booster seems to be the best—Pfizer to Moderna booster, Moderna to Pfizer for booster, and J&J should switch to Moderna / Pfizer booster. HT to @ScientistSwanda. #COVID19 #BoosterShots #vaccinate https://t.co/Yw0R6atC7i
Assessment of Cognitive Function in Patients After COVID-19 Infection | Dementia and Cognitive Impairment | JAMA Network Open | JAMA Network
This cross-sectional study examines rates of cognitive impairment among patients who survived COVID-19 and whether the care setting was associated with cognitive impairment rates.
(1) Jan Hartmann auf Twitter: "Grandiose neue Daten zu Boost mit 3.Dosis BioNTech. 1. Klinische Daten: Placebokontrollierte Phase 3-Studie zeigt nochmalige (!) 95.6%ige Reduktion von symptomatischer Infektion durch Delta bei 3x Geimpften im Vgl. zu 2x Geimpften. https://t.co/MewlICh9en" / Twitter
Grandiose neue Daten zu Boost mit 3.Dosis BioNTech.
1. Klinische Daten: Placebokontrollierte Phase 3-Studie zeigt nochmalige (!) 95.6%ige Reduktion von symptomatischer Infektion durch Delta bei 3x Geimpften im Vgl. zu 2x Geimpften.
https://t.co/MewlICh9en
(1) Konrad Steinestel auf Twitter: "Die Autoren zeigen, dass Makrophagen (zur Aufnahme von Partikeln fähige Immunzellen) von COVID-Patienten nach Kontakt mit dem Spike-Protein spezielle Zellorganellen (das Inflammasom) bilden, welches einen Botenstoff (IL-1beta) spaltet u freisetzt. https://t.co/eMPMnjOchE" / Twitter
Die Autoren zeigen, dass Makrophagen (zur Aufnahme von Partikeln fähige Immunzellen) von COVID-Patienten nach Kontakt mit dem Spike-Protein spezielle Zellorganellen (das Inflammasom) bilden, welches einen Botenstoff (IL-1beta) spaltet u freisetzt. https://t.co/eMPMnjOchE
New data suggests Canada's 'gamble' on delaying, mixing and matching COVID-19 vaccines paid off | CBC News
New Canadian data suggests the strategy to delay and mix second doses of COVID-19 vaccines led to strong protection from infection, hospitalization and death — even against the highly contagious delta variant — that could provide lessons for the world.
Spätfolgen einer Virus-Myokarditis: Viele sterben binnen 10 Jahre
Die 10-Jahres-Sterblichkeit nach einer durch Viren ausgelösten Myokarditis ist hoch. Deutsche Kardiologen haben nun untersucht, welche Patienten besonders gefährdet sind.
Großangelegte Metaanalyse: Long Covid trifft Hälfte der Genesenen
Auch nach überstandener Covid-19-Erkrankung fühlen sich viele Menschen noch nicht wieder richtig gesund. Forscher wollen wissen, wie viele Genesene von Long Covid betroffen sind und unter welchen Symptomen sie genau leiden und liefern Erkenntnisse.
Differential immunogenicity of homologous versus heterologous boost in Ad26.COV2.S vaccine recipients
Protection offe red by COVID-19 vaccines wanes over time, requi ring an eval uation of
different boos ti ng s trategies to revert suc h a trend and enhance the quanti ty and quality of
Spike-s pecific humoral and cellu lar i mmune responses . T hes e immunolo gic al parameters in
homologous or heterologous vaccination boosts have thus far been studied for mRNA and
ChAdO x1 nCoV-19 vaccines, but knowledge on indi viduals who received a s ingle dose of
Ad26.COV2.S is lacking.
We studied Spike-specific humoral and cellular immun ity in Ad26.CO V2.S vac cinated
individuals (n=55) who were eith er pr imed with Ad26.COV2.S only (n=13), or boosted with a
homologous (Ad26.COV2.S, n=28) or heterol ogous (BNT162b2, n=14) second dose. W e
compared our findings with the res ul ts found in i ndiv iduals vaccinated with a single (n=16)
or double (n=44) dos e of BN T162b2. W e obs erved tha t a strategy of heterologous
vaccination enhanc ed the quanti ty and breadth of b oth, Spike-specific humoral and cellular
immunity in Ad26.CO V2.S vaccinated. In contras t, the impa ct of h omol ogous boost was
quanti tati vely minimal in Ad26.COV2.S vacc inate d and Spike-speci fic antibodies and T cells
were narrowly focus ed to the S1 region. Al though a direct ass ociation between quantity and
quality of immuno logic al parameters and in vivo protec ti on has not been demonstrated, the
immunol og ical features of Spike-spec ifi c humora l and cellular immune r esponses s upport
the utili zation of a heter ologous s trategy of vacc ine boos t in individuals who receiv ed
Ad26.COV2.S vaccination.
Following severe adverse reactions to the AstraZeneca ChAdOx1-S-nCoV-19 vaccine1,2, European health authorities have recommended that patients under the age of 55 who received one dose of ChAdOx1-S-nCoV-19 vaccine receive a second dose of Pfizer BNT162b2 vaccine as a booster. However, the effectiveness and the immunogenicity of this vaccination regimen have not been formally tested. Here, we show that the heterologous ChAdOx1-S-nCoV-19/BNT162b2 combination confers better protection against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection than the homologous BNT162b2/BNT162b2 combination in a real-world observational study of healthcare workers (n=13121). To understand the underlying mechanism, we conducted a longitudinal survey of the anti-spike immunity conferred by each vaccine combination. Both combinations induced strong anti-spike antibody (Ab) responses but sera from heterologous vaccinated individuals displayed a stronger neutralizing activity, regardless of the SARS-CoV-2 variant. This enhanced neutralizing potential was correlated with increased frequencies of switched and activated memory B cells recognizing the SARS-CoV-2 Receptor Binding Domain (RBD). The ChAdOx1-S-nCoV-19 vaccine induced a weaker IgG response but a stronger T cell response than the BNT162b2 vaccine after the priming dose, which could explain the complementarity of both vaccines when used in combination. The heterologous vaccination regimen could therefore be particularly suitable for immune compromised individuals.
Long-term immunogenicity of BNT162b2 vaccination in older people and younger health-care workers
The COVID-19 mRNA vaccine BNT162b2 (Comirnaty) is highly immunogenic and effective
in preventing severe illness.1 Studies have indicated decreasing anti-SARS-CoV-2 antibody
concentrations, but largely stable vaccine efficacy and effectiveness 6 months after
vaccination.2,3 The emergence of variants of concern (VOCs), such as the delta (B.1.617.2)
VOC, has raised concerns about waning protection, particularly in high-risk populations
such as older people, who display lower immune responses to BNT162b2 vaccination than
younger adults.