A5039562805- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Animal Virus Infections Studies
- SARS-CoV-2 detection and testing
- Viral gastroenteritis research and epidemiology
- Bacillus and Francisella bacterial research
- Infectious Encephalopathies and Encephalitis
- Long-Term Effects of COVID-19
- Immunotherapy and Immune Responses
- Respiratory viral infections research
- Birth, Development, and Health
- Renal Diseases and Glomerulopathies
- Electrolyte and hormonal disorders
- Vitamin D Research Studies
- Bacterial Infections and Vaccines
- Immune responses and vaccinations
- Viral Infections and Immunology Research
- Pregnancy and preeclampsia studies
- Reproductive System and Pregnancy
- Organ Transplantation Techniques and Outcomes
- Pleural and Pulmonary Diseases
- Monoclonal and Polyclonal Antibodies Research
- Effects and risks of endocrine disrupting chemicals
- Renal Transplantation Outcomes and Treatments
- Virus-based gene therapy research
Beth Israel Deaconess Medical Center
2021-2024
Harvard University
2024
Hadassah Medical Center
2023-2024
University of Toronto
2021-2023
NHS Blood and Transplant
1973
Spike-specific neutralizing antibodies (NAbs) are generally considered key correlates of vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Recently, robust prevention disease with SARS-CoV-2 variants that largely escape NAb responses has been reported, suggesting a role for other immune parameters virologic control. However, direct data demonstrating CD8+ T cells in have not yet reported. In this study, we show vaccine-elicited contribute...
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variant BA.2.86 has over 30 mutations in spike compared with BA.2 and XBB.1.5, which raised the possibility that might evade neutralizing antibodies (NAbs) induced by vaccination or infection. In this study, we show NAb titers are substantially lower to but similar slightly higher than other current circulating variants, including EG.5.1, FL.1.5.1. Moreover, against all these variants were vaccinated individuals a history of...
The rapid spread of the SARS-CoV-2 Omicron (B.1.1.529) variant, including in highly vaccinated populations, has raised important questions about efficacy current vaccines. In this study, we show that mRNA-based BNT162b2 vaccine and adenovirus-vector-based Ad26.COV2.S provide robust protection against high-dose challenge with variant cynomolgus macaques. We 30 macaques homologous heterologous prime-boost regimens Ad26.COV2.S. Following challenge, demonstrated control virus bronchoalveolar...
Abstract The SARS-CoV-2 Omicron variant has continued to evolve. XBB is a recombinant between two BA.2 sublineages, XBB.1 includes the G252V mutation, and XBB.1.5 F486P mutations. rapidly increased in frequency become dominant virus New England. bivalent mRNA vaccine boosters have been shown increase neutralizing antibody (NAb) titers multiple variants, but durability of these responses remains be determined. We assessed humoral cellular immune 30 participants who received performed assays...
Abstract A limitation of current SARS-CoV-2 vaccines is that they provide minimal protection against infection with Omicron subvariants 1,2 , although still severe disease. Enhanced mucosal immunity may be required to block and onward transmission. Intranasal administration has proven inconsistent 3–7 suggesting alternative immunization strategies required. Here we show intratracheal boosting a bivalent Ad26-based vaccine results in substantial induction humoral cellular near-complete BQ.1.1...
ABSTRACT The SARS-CoV-2 Omicron variant (B.1.1.529) has three major lineages BA.1, BA.2, and BA.3 1 . BA.1 rapidly became dominant demonstrated substantial escape from neutralizing antibodies (NAbs) induced by vaccination 2-4 BA.2 recently increased in frequency multiple regions of the world, suggesting that a selective advantage over BA.1. share common mutations, but both also have unique mutations ( Fig. 1A ). ability to evade NAbs or infection not yet been reported. We evaluated WA1/2020,...
ABSTRACT The continued evolution of SARS-CoV-2 may lead to evasion vaccine immunity and natural immunity. A highly mutated Omicron variant BA.2.86 has recently been identified with over 30 amino acid changes in Spike compared BA.2 XBB.1.5. As September 4, 2023, 37 sequences from 10 countries, which is likely an underestimate due limited surveillance. ability evade NAbs other currently circulating variants remains unknown. Our data show that NAb responses were lower than but comparable or...
Messenger RNA (mRNA) vaccines were highly effective against the ancestral SARS-CoV-2 strain, but efficacy of bivalent mRNA boosters XBB variants was substantially lower. Here, we show limited durability neutralizing antibody (NAb) responses and isotype switching to immunoglobulin G4 (IgG4) following boosting. Bivalent boosting elicited modest XBB.1-, XBB.1.5-, XBB.1.16-specific NAbs that waned rapidly within 3 months. In contrast, induced more robust sustained WA1/2020 suggesting immune...
Omicron spike (S) encoding vaccines as boosters, are a potential strategy to improve COVID-19 vaccine efficacy against Omicron. Here, macaques (mostly females) previously immunized with Ad26.COV2.S, boosted Ad26.COV2.S.529 (encoding BA.1 S) or 1:1 combination of both vaccines. All booster vaccinations elicit rapid antibody titers increase WA1/2020 and S. BA.2 responses most effectively by including Ad26.COV2.S.529. Independent used, mostly WA1/2020-reactive WA1/2020-Omicron cross-reactive B...
Current COVID-19 vaccines provide robust protection against severe disease but minimal acquisition of infection. Intramuscularly administered induce serum neutralizing antibodies (NAbs), their ability to boost mucosal immune responses remains be determined. In this study, we show that the XBB.1.5 messenger RNA (mRNA) boosters result in increased neutralization multiple acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants humans, including dominant circulating variant JN.1....
Waning immunity following mRNA vaccination and the emergence of SARS-CoV-2 variants has led to reduced vaccine efficacy against both symptomatic infection severe disease. Bivalent boosters expressing Omicron BA.5 ancestral WA1/2020 Spike proteins have been developed approved, because is currently dominant variant substantially evades neutralizing antibodies (NAbs). Our data show that NAb titers were comparable monovalent bivalent boosters.
ABSTRACT Multiple lineages of the SARS-CoV-2 Omicron variant (B.1.1.529) have emerged, and BA.1 BA.2 demonstrated substantial escape from neutralizing antibodies (NAbs). BA.2.12.1 has now become dominant in United States, BA.4 BA.5 South Africa. Our data show that BA.4/BA.5 substantially NAbs induced by both vaccination infection. Moreover, NAb titers, to lesser extent were lower than suggesting continued evolve with increasing neutralization escape. These findings important public health...
Abstract Despite the availability of several effective SARS-CoV-2 vaccines, additional vaccines will be required for optimal global vaccination. In this study, we investigate immunogenicity and protective efficacy GBP510 protein subunit vaccine adjuvanted with AS03, which has recently been authorized marketing in South Korea under trade name SKYCovione TM . The antigen GBP510/AS03 is a two-part recombinant nanoparticle, displays 60 receptor binding domain (RBD) proteins Spike on its surface....
Abstract Background In North America, both messenger RNA (mRNA) vaccines, Pfizer-BioNTech BNT162b2, and Moderna mRNA-1273, each utilizing a 2-dose regimen, have started to be administered individuals. Methods We evaluated the quantitative serologic antibody response following administration of either single dose or doses an mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in cohort 98 participants (88 healthcare workers [HCW] 10 solid organ transplant [SOT]...
ABSTRACT Omicron BA.5 has been the globally dominant SARS-CoV-2 variant and demonstrated substantial neutralization escape compared with prior variants. Additional variants have recently emerged, including BA.4.6, BF.7, BA.2.75.2, BQ.1.1, all of which Spike R346T mutation. In particular, BQ.1.1 rapidly increased in frequency, declined to less than half viruses United States. Our data demonstrate that BA.2.75.2 NAbs induced by infection vaccination more effectively BA.5. NAb titers were lower...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines demonstrate reduced protection against acquisition of BA.5 subvariant but are still effective severe disease. However, immune correlates remain unknown. We report the immunogenicity and protective efficacy vaccine regimens consisting vector-based Ad26.COV2.S adjuvanted spike ferritin nanoparticle (SpFN) a high-dose, mismatched Omicron challenge in macaques. The SpFNx3 Ad26 + SpFNx2 elicit higher antibody responses than...
Abstract The rapid spread of the highly mutated SARS-CoV-2 Omicron variant has raised substantial concerns about protective efficacy currently available vaccines. We assessed Omicron-specific humoral and cellular immune responses in 65 individuals who were vaccinated with two immunizations BNT162b2 boosted after at least 6 months either Ad26.COV2.S (Johnson & Johnson; N=41) or (Pfizer; N=24) (Table S1).
Abstract Background Preeclampsia is a multisystem disorder defined by new onset of hypertension with proteinuria after 20 weeks gestation. In part due to dysregulation pro-angiogenic factors (e.g., placental growth factor [PlGF]) and anti-angiogenic soluble fms-like tyrosine kinase 1 [sFlt-1]), preeclampsia results in decreased perfusion. An increased sFlt-1:PlGF ratio associated risk preeclampsia. this study, we evaluated cutoffs the clinical performance for predicting Methods from 130...
Abstract The COVID-19 pandemic marks the third coronavirus this century (SARS-CoV-1, MERS, SARS-CoV-2), emphasizing need to identify and evaluate conserved immunogens for a pan-sarbecovirus vaccine. Here we investigate potential utility of T-cell vaccine strategy targeting regions sarbecovirus proteome. We identified most proteome as portions RNA-dependent RNA polymerase (RdRp) Helicase proteins, both which are part replication transcription complex (RTC). Fitness constraints suggest that...
Abstract Long Covid, or Post-Acute Sequelae of COVID-19 (PASC), involves a spectrum chronic symptoms following resolution acute SARS-CoV-2 infection. Current hypotheses for the pathogenesis Covid include persistent SARS-CoV-2, activation other viruses, tissue damage, autoimmunity, endocrine insufficiency, immune dysfunction, and complement activation. We evaluated 142 participants, including uninfected controls (N=35), acutely infected individuals (N=54), convalescent (N=25), patients...