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Immunogenicity of NVX-CoV2373 heterologous boost against SARS-CoV-2 variants

Lyke, Kirsten E; Atmar, Robert L; Dominguez Islas, Clara; Posavad, Christine M; Deming, Meagan E; Branche, Angela R; Johnston, Christine; El Sahly, Hana M; Edupuganti, Srilatha; Mulligan, Mark J; Jackson, Lisa A; Rupp, Richard E; Rostad, Christina A; Coler, Rhea N; Bäcker, Martín; Kottkamp, Angelica C; Babu, Tara M; Dobrzynski, David; Martin, Judith M; Brady, Rebecca C; Frenck, Robert W; Rajakumar, Kumaravel; Kotloff, Karen; Rouphael, Nadine; Szydlo, Daniel; PaulChoudhury, Rahul; Archer, Janet I; Crandon, Sonja; Ingersoll, Brian; Eaton, Amanda; Brown, Elizabeth R; McElrath, M Juliana; Neuzil, Kathleen M; Stephens, David S; Post, Diane J; Lin, Bob C; Serebryannyy, Leonid; Beigel, John H; Montefiori, David C; Roberts, Paul C
As part of a multicenter study evaluating homologous and heterologous COVID-19 booster vaccines, we assessed the magnitude, breadth, and short-term durability of binding and pseudovirus-neutralizing antibody (PsVNA) responses following a single booster dose of NVX-CoV2373 in adults primed with either Ad26.COV2.S, mRNA-1273, or BNT162b2 vaccines. NVX-CoV2373 as a heterologous booster was immunogenic and associated with no safety concerns through Day 91. Fold-rises in PsVNA titers from baseline (Day 1) to Day 29 were highest for prototypic D614G variant and lowest for more recent Omicron sub-lineages BQ.1.1 and XBB.1. Peak humoral responses against all SARS-CoV-2 variants were lower in those primed with Ad26.COV2.S than with mRNA vaccines. Prior SARS CoV-2 infection was associated with substantially higher baseline PsVNA titers, which remained elevated relative to previously uninfected participants through Day 91. These data support the use of heterologous protein-based booster vaccines as an acceptable alternative to mRNA or adenoviral-based COVID-19 booster vaccines. This trial was conducted under NCT04889209.
PMID: 37433788
ISSN: 2059-0105
CID: 5537552

The COVID-19 Pandemic Unmasked the Challenges Faced by Early-Stage Faculty in Infectious Diseases: A Call to Action

Scherer, Erin M; Backer, Martin; Carvajal, Karen; Danziger-Isakov, Lara; Frey, Sharon; Howard, Leigh M; Huang, Felicia Scaggs; Kottkamp, Angelica C; Reid, Tara; Rodriguez-Barradas, Maria C; Karita, Helen C Stankiewicz; Teoh, Zheyi; Wald, Anna; Whitaker, Jennifer; Wiley, Zanthia; Ofotokun, Igho; Edwards, Kathryn M
The COVID-19 pandemic and associated increase in family care responsibilities resulted in unsustainable personal and professional workloads for Infectious Diseases (ID) faculty on the front lines. This was especially true for early-stage faculty (ESF), many of whom had caregiving responsibilities. In addition, women faculty, underrepresented in medicine and science faculty, and particularly ESF experienced marked declines in research productivity, which significantly impacts career trajectories. When combined with staffing shortages due to an aging workforce and suboptimal recruitment and retention in ID, these work-life imbalances have brought the field to an inflection point. We propose actionable recommendations and call on ID leaders to act to close the gender, racial, and ethnic gaps to improve the recruitment, retention, and advancement of ESF in ID. By investing in systemic change to make the ID workforce more equitable, we can embody the shared ideals of diversity and inclusion and prepare for the next pandemic.
PMID: 36131321
ISSN: 1537-6591
CID: 5335452


Wang, Shan; Banta, Erin; Backer, Martin; Baltazar, Gerard; Joseph, D\Andrea; Winner, Megan
ISSN: 0090-3493
CID: 5496522

Rapid decline in vaccine-boosted neutralizing antibodies against SARS-CoV-2 Omicron variant

Lyke, Kirsten E; Atmar, Robert L; Islas, Clara Dominguez; Posavad, Christine M; Szydlo, Daniel; Paul Chourdhury, Rahul; Deming, Meagan E; Eaton, Amanda; Jackson, Lisa A; Branche, Angela R; El Sahly, Hana M; Rostad, Christina A; Martin, Judith M; Johnston, Christine; Rupp, Richard E; Mulligan, Mark J; Brady, Rebecca C; Frenck, Robert W; Bäcker, Martín; Kottkamp, Angelica C; Babu, Tara M; Rajakumar, Kumaravel; Edupuganti, Srilatha; Dobrzynski, David; Coler, Rhea N; Archer, Janet I; Crandon, Sonja; Zemanek, Jillian A; Brown, Elizabeth R; Neuzil, Kathleen M; Stephens, David S; Post, Diane J; Nayak, Seema U; Suthar, Mehul S; Roberts, Paul C; Beigel, John H; Montefiori, David C
The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits reduced susceptibility to vaccine-induced neutralizing antibodies, requiring a boost to generate protective immunity. We assess the magnitude and short-term durability of neutralizing antibodies after homologous and heterologous boosting with mRNA and Ad26.COV2.S vaccines. All prime-boost combinations substantially increase the neutralization titers to Omicron, although the boosted titers decline rapidly within 2 months from the peak response compared with boosted titers against the prototypic D614G variant. Boosted Omicron neutralization titers are substantially higher for homologous mRNA vaccine boosting, and for heterologous mRNA and Ad26.COV2.S vaccine boosting, compared with homologous Ad26.COV2.S boosting. Homologous mRNA vaccine boosting generates nearly equivalent neutralizing activity against Omicron sublineages BA.1, BA.2, and BA.3 but modestly reduced neutralizing activity against BA.2.12.1 and BA.4/BA.5 compared with BA.1. These results have implications for boosting requirements to protect against Omicron and future variants of SARS-CoV-2. This trial was conducted under NCT04889209.
PMID: 35798000
ISSN: 2666-3791
CID: 5278372

Children Lagging with COVID-19 Vaccination

Noor, Asif; Backer, Martin; Krilov, Leonard R
Children account for a growing share of coronavirus disease 2019 (COVID-19) infections in the United States. Since the widespread availability of COVID-19 vaccine in adults, there has been an upward trend of cases in children, accounting for approximately 20% of the weekly new cases. The majority (38.3%) reported in high school students age 14 to 17 years. Children are also at risk of a postinflammatory condition, known as multisystem inflammatory syndrome in children, after COVID-19. In addition, infected children could transmit the virus to vulnerable adults, contributing to ongoing pandemic. We believe that children need to be vaccinated against COVID-19 and review the available evidence. [Pediatr Ann. 2022;51(5):e180-e185.].
PMID: 35575538
ISSN: 1938-2359
CID: 5294102

Homologous and Heterologous Covid-19 Booster Vaccinations

Atmar, Robert L; Lyke, Kirsten E; Deming, Meagan E; Jackson, Lisa A; Branche, Angela R; El Sahly, Hana M; Rostad, Christina A; Martin, Judith M; Johnston, Christine; Rupp, Richard E; Mulligan, Mark J; Brady, Rebecca C; Frenck, Robert W; Bäcker, Martín; Kottkamp, Angelica C; Babu, Tara M; Rajakumar, Kumaravel; Edupuganti, Srilatha; Dobrzynski, David; Coler, Rhea N; Posavad, Christine M; Archer, Janet I; Crandon, Sonja; Nayak, Seema U; Szydlo, Daniel; Zemanek, Jillian A; Dominguez Islas, Clara P; Brown, Elizabeth R; Suthar, Mehul S; McElrath, M Juliana; McDermott, Adrian B; O'Connell, Sarah E; Montefiori, David C; Eaton, Amanda; Neuzil, Kathleen M; Stephens, David S; Roberts, Paul C; Beigel, John H
BACKGROUND:Although the three vaccines against coronavirus disease 2019 (Covid-19) that have received emergency use authorization in the United States are highly effective, breakthrough infections are occurring. Data are needed on the serial use of homologous boosters (same as the primary vaccine) and heterologous boosters (different from the primary vaccine) in fully vaccinated recipients. METHODS:virus particles, or BNT162b2 (Pfizer-BioNTech) at a dose of 30 μg. The primary end points were safety, reactogenicity, and humoral immunogenicity on trial days 15 and 29. RESULTS:Of the 458 participants who were enrolled in the trial, 154 received mRNA-1273, 150 received Ad26.COV2.S, and 153 received BNT162b2 as booster vaccines; 1 participant did not receive the assigned vaccine. Reactogenicity was similar to that reported for the primary series. More than half the recipients reported having injection-site pain, malaise, headache, or myalgia. For all combinations, antibody neutralizing titers against a SARS-CoV-2 D614G pseudovirus increased by a factor of 4 to 73, and binding titers increased by a factor of 5 to 55. Homologous boosters increased neutralizing antibody titers by a factor of 4 to 20, whereas heterologous boosters increased titers by a factor of 6 to 73. Spike-specific T-cell responses increased in all but the homologous Ad26.COV2.S-boosted subgroup. CD8+ T-cell levels were more durable in the Ad26.COV2.S-primed recipients, and heterologous boosting with the Ad26.COV2.S vaccine substantially increased spike-specific CD8+ T cells in the mRNA vaccine recipients. CONCLUSIONS:Homologous and heterologous booster vaccines had an acceptable safety profile and were immunogenic in adults who had completed a primary Covid-19 vaccine regimen at least 12 weeks earlier. (Funded by the National Institute of Allergy and Infectious Diseases; DMID 21-0012 number, NCT04889209.).
PMID: 35081293
ISSN: 1533-4406
CID: 5154552

The Coronavirus Disease 2019 Pandemic Unmasked the Challenges Faced by Early-Stage Faculty in Infectious Diseases: A Call to Action

Scherer, Erin M.; Backer, Martin; Carvajal, Karen; Danziger-Isakov, Lara; Frey, Sharon; Howard, Leigh M.; Huang, Felicia Scaggs; Kottkamp, Angelica C.; Reid, Tara; Rodriguez-Barradas, Maria C.; Karita, Helen C. Stankiewicz; Teoh, Zheyi; Wald, Anna; Whitaker, Jennifer; Wiley, Zanthia; Ofotokun, Igho; Edwards, Kathryn M.
ISSN: 1058-4838
CID: 5388632

Treating COVID-19 With Hydroxychloroquine (TEACH): A Multicenter, Double-Blind Randomized Controlled Trial in Hospitalized Patients

Ulrich, Robert J; Troxel, Andrea B; Carmody, Ellie; Eapen, Jaishvi; Bäcker, Martin; DeHovitz, Jack A; Prasad, Prithiv J; Li, Yi; Delgado, Camila; Jrada, Morris; Robbins, Gabriel A; Henderson, Brooklyn; Hrycko, Alexander; Delpachitra, Dinuli; Raabe, Vanessa; Austrian, Jonathan S; Dubrovskaya, Yanina; Mulligan, Mark J
Background/UNASSIGNED:Effective therapies to combat coronavirus 2019 (COVID-19) are urgently needed. Hydroxychloroquine (HCQ) has in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the clinical benefit of HCQ in treating COVID-19 is unclear. Randomized controlled trials are needed to determine the safety and efficacy of HCQ for the treatment of hospitalized patients with COVID-19. Methods/UNASSIGNED:We conducted a multicenter, double-blind randomized clinical trial of HCQ among patients hospitalized with laboratory-confirmed COVID-19. Subjects were randomized in a 1:1 ratio to HCQ or placebo for 5 days and followed for 30 days. The primary efficacy outcome was a severe disease progression composite end point (death, intensive care unit admission, mechanical ventilation, extracorporeal membrane oxygenation, and/or vasopressor use) at day 14. Results/UNASSIGNED: = .350). There were no significant differences in COVID-19 clinical scores, number of oxygen-free days, SARS-CoV-2 clearance, or adverse events between HCQ and placebo. HCQ was associated with a slight increase in mean corrected QT interval, an increased D-dimer, and a trend toward an increased length of stay. Conclusions/UNASSIGNED:In hospitalized patients with COVID-19, our data suggest that HCQ does not prevent severe outcomes or improve clinical scores. However, our conclusions are limited by a relatively small sample size, and larger randomized controlled trials or pooled analyses are needed.
PMID: 33134417
ISSN: 2328-8957
CID: 4655862

Pediatric Fistula Initiative: Reducing Bloodstream Infections in an Outpatient Pediatric Hemodialysis Center

Chotikanatis, Kobkul; Suman, Nisha; Bäcker, Martin; Paudyal, Bandana; Schoeneman, Morris; Kohlhoff, Stephan; Hammerschlag, Margaret R
Bloodstream infection is a major contributor to morbidity and mortality in children on hemodialysis (HD). From January 2009 through April 2011, the incidence of access-related bloodstream infections (ARBs) in pediatric patients on HD at our hospital was 3.45/1000 patient days. Almost all of these children were receiving HD via central line catheters, and none were receiving HD via arteriovenous fistulas (AVFs). In an effort to reduce the rate of infection in children receiving HD at our institution, we introduced the Pediatric Fistula Initiative, a program to increase creation and use of AVFs in children. Thirty-three children on HD were observed, 9 of whom received AVFs during the study period. The incidence of ARBs decreased to 1.30/1000 patient days (P < .001) during the 24-month intervention period from May 2011 through May 2013.
PMID: 26582876
ISSN: 2048-7207
CID: 4591402

Membrane-bound SIV envelope trimers are immunogenic in ferrets after intranasal vaccination with a replication-competent canine distemper virus vector

Zhang, Xinsheng; Wallace, Olivia; Wright, Kevin J; Backer, Martin; Coleman, John W; Koehnke, Rebecca; Frenk, Esther; Domi, Arban; Chiuchiolo, Maria J; DeStefano, Joanne; Narpala, Sandeep; Powell, Rebecca; Morrow, Gavin; Boggiano, Cesar; Zamb, Timothy J; Richter King, C; Parks, Christopher L
We are investigating canine distemper virus (CDV) as a vaccine vector for the delivery of HIV envelope (Env) that closely resembles the native trimeric spike. We selected CDV because it will promote vaccine delivery to lymphoid tissues, and because human exposure is infrequent, reducing potential effects of pre-existing immunity. Using SIV Env as a model, we tested a number of vector and gene insert designs. Vectors containing a gene inserted between the CDV H and L genes, which encoded Env lacking most of its cytoplasmic tail, propagated efficiently in Vero cells, expressed the immunogen on the cell surface, and incorporated the SIV glycoprotein into progeny virus particles. When ferrets were vaccinated intranasally, there were no signs of distress, vector replication was observed in the gut-associated lymphoid tissues, and the animals produced anti-SIV Env antibodies. These data show that live CDV-SIV Env vectors can safely induce anti-Env immune responses following intranasal vaccination.
PMID: 24074564
ISSN: 1096-0341
CID: 4591392