Nirsevimab, a monoclonal antibody with an extended half-life, is designed to protect infants from respiratory syncytial virus disease after a single intramuscular dose. This placebo-controlled trial ...involving 1447 preterm infants at 164 sites in 23 countries assessed the effectiveness of nirsevimab over 150 days after the dose was administered.
Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine Heath, Paul T; Galiza, Eva P; Baxter, David N ...
New England journal of medicine/The New England journal of medicine,
09/2021, Letnik:
385, Številka:
13
Journal Article
Recenzirano
Odprti dostop
In a phase 3 trial involving more than 15,000 participants, two doses of NVX-CoV2373, a recombinant SARS-CoV-2 nanoparticle vaccine, administered 21 days apart had a vaccine efficacy of 89.7%. ...Reactogenicity was generally mild and transient, and adverse events were infrequent and of low grade.
BACKGROUND:MEDI8897 is a recombinant human monoclonal antibody being developed for prophylaxis of serious respiratory syncytial virus (RSV) disease in all infants.
METHODS:In this phase 1b/2a ...dose-escalation study, healthy preterm infants with a gestational age of 32–35 weeks were randomized to receive a single intramuscular injection of MEDI8897 (10, 25 or 50 mg) or placebo. Safety, pharmacokinetics, RSV-neutralizing antibody and antidrug antibody (ADA) assessments were performed during the 360-day follow-up period. Infants who experienced medically attended lower respiratory tract infections (LRTIs) were tested for RSV.
RESULTS:MEDI8897 serum half-life ranged from 62.5–72.9 days. On day 151, 87% of infants in the 50 mg group had serum concentrations above the 90% effective concentration target level of 6.8 µg/mL, and 90% showed a ≥4-fold rise from baseline in serum RSV-neutralizing antibody levels. Adverse events (AEs) were reported in 17 of 18 (94.4%) placebo and 66 of 71 (93.0%) MEDI8897 recipients. Three MEDI8897 recipients experienced 5 serious AEs (3 LRTIs, 2 febrile seizures). ADA was detected at any time postbaseline in 28.2% of MEDI8897 recipients and at day 361 only in 26.5% of subjects. ADA response was not associated with AEs. Five (7%) MEDI8897 recipients experienced medically attended LRTIs through day 150; 1 tested positive for RSV (10 mg group).
CONCLUSIONS:MEDI8897 had a favorable safety profile in healthy preterm infants. The extended half-life of MEDI8897 and demonstrated RSV-neutralizing activity support protection from RSV for the duration of a typical 5-month season after a single 50 mg intramuscular (IM) dose.
NVX-CoV2373 is a recombinant severe acute respiratory coronavirus 2 (rSARS-CoV-2) nanoparticle vaccine composed of trimeric full-length SARS-CoV-2 spike glycoproteins and Matrix-M1 adjuvant. The ...phase 2 component of our randomized, placebo-controlled, phase 1 to 2 trial was designed to identify which dosing regimen of NVX-CoV2373 should move forward into late-phase studies and was based on immunogenicity and safety data through Day 35 (14 days after the second dose). The trial was conducted at 9 sites in Australia and 8 sites in the United States. Participants in 2 age groups (aged 18 to 59 and 60 to 84 years) were randomly assigned to receive either 1 or 2 intramuscular doses of 5-mug or 25-mug NVX-CoV2373 or placebo, 21 days apart. Primary endpoints were immunoglobulin G (IgG) anti-spike protein response, 7-day solicited reactogenicity, and unsolicited adverse events. A key secondary endpoint was wild-type virus neutralizing antibody response. After enrollment, 1,288 participants were randomly assigned to 1 of 4 vaccine groups or placebo, with 1,283 participants administered at least 1 study treatment. Of these, 45% were older participants 60 to 84 years. Reactogenicity was predominantly mild to moderate in severity and of short duration (median <3 days) after first and second vaccination with NVX-CoV2373, with higher frequencies and intensity after second vaccination and with the higher dose. Reactogenicity occurred less frequently and was of lower intensity in older participants. Both 2-dose regimens of 5-mug and 25-mug NVX-CoV2373 induced robust immune responses in younger and older participants. For the 2-dose regimen of 5 mug, geometric mean titers (GMTs) for IgG anti-spike protein were 65,019 (95% confidence interval (CI) 55,485 to 76,192) and 28,137 (95% CI 21,617 to 36,623) EU/mL and for wild-type virus neutralizing antibody (with an inhibitory concentration of 50%-MN.sub.50%) were 2,201 (95% CI 1,343 to 3,608) and 981 (95% CI 560 to 1,717) titers for younger and older participants, respectively, with seroconversion rates of 100% in both age groups. Neutralizing antibody responses exceeded those seen in a panel of convalescent sera for both age groups. Study limitations include the relatively short duration of safety follow-up to date and current lack of immune persistence data beyond the primary vaccination regimen time point assessments, but these data will accumulate over time. The study confirmed the phase 1 findings that the 2-dose regimen of 5-mug NVX-CoV2373 is highly immunogenic and well tolerated in younger adults. In addition, in older adults, the 2-dose regimen of 5 mug was also well tolerated and showed sufficient immunogenicity to support its use in late-phase efficacy studies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Monovalent SARS-CoV-2 Prototype (Wuhan-Hu-1) and bivalent (Prototype + BA.4/5) COVID-19 vaccines have demonstrated a waning of vaccine-mediated immunity highlighted by lower neutralizing ...antibody responses against SARS-CoV-2 Omicron XBB sub-variants. The reduction of humoral immunity due to the rapid evolution of SARS-CoV-2 has signaled the need for an update to vaccine composition. A strain change for all authorized/approved vaccines to a monovalent composition with Omicron subvariant XBB.1.5 has been supported by the WHO, EMA, and FDA. Here, we demonstrate that immunization with a monovalent recombinant spike protein COVID-19 vaccine (Novavax, Inc.) based on the subvariant XBB.1.5 induces neutralizing antibodies against XBB.1.5, XBB.1.16, XBB.2.3, EG.5.1, and XBB.1.16.6 subvariants, promotes higher pseudovirus neutralizing antibody titers than bivalent (Prototype + XBB.1.5) vaccine, induces SARS-CoV-2 spike-specific Th1-biased CD4 + T-cell responses against XBB subvariants, and robustly boosts antibody responses in mice and nonhuman primates primed with a variety of monovalent and bivalent vaccines. Together, these data support updating the Novavax vaccine to a monovalent XBB.1.5 formulation for the 2023–2024 COVID-19 vaccination campaign.
Highlights ► Influenza B strains from 2 lineages co-circulate, but vaccines contain 1 B strain. ► Q/LAIV (live attenuated influenza vaccine with 2 B strains) was studied in adults. ► The ...immunogenicity of Q/LAIV was noninferior to that of trivalent LAIV. ► The safety profile of Q/LAIV was similar to that of T/LAIV.
Despite substantial morbidity associated with respiratory syncytial virus (RSV) infection, there is no licensed vaccine. MEDI-559 is a live attenuated intranasal vaccine candidate being developed for ...prevention of lower respiratory illness due to RSV in young children. This randomized, placebo-controlled study evaluated safety of MEDI-559 in healthy, RSV-seronegative children. MEDI-559 or placebo was administered on 3 occasions, 2 months apart. Primary safety was based on solicited symptoms (SSs) and adverse events (AEs) collected for 28 days after each dose. Nasal wash samples were collected 3 times after each dose (days 7-10, 12-18, 28-34) and at sick visits. Serum was collected for measuring antibody immune responses to RSV prior to first vaccination and 28 days post final dose. Long-term safety was monitored for 365 days from first dose. SSs were mild and frequent (MEDI-559 84%; placebo 91%); most common SSs were runny/stuffy nose, cough, and irritability/fussiness. AEs occurred in 67% MEDI-559 and 57% placebo recipients: most common AE was upper respiratory tract infection (MEDI-559 35%; placebo 23%). Higher incidence of medically attended lower respiratory illness within 28 days after dosing occurred in the MEDI-559 arm compared to placebo (none associated with vaccine virus shedding). There was no evidence of enhanced RSV disease. Vaccine virus was detected only in MEDI-559 recipients; shedding occurred in 56%subjects, primarily post dose 1. A functional immune response was observed in 59% and 9% MEDI-559 and placebo recipients, respectively, by an RSV microneutralization assay. Vaccine take, assessed by proportion that shed vaccine-type virus or had a seroresponse against RSV, was seen in 95% MEDI-559 subjects. MEDI-559 is therefore biologically active and immunogenic in this seronegative pediatric population. Although the frequency of SSs and AEs was not considered clinically significant, the increase in medically attended lower respiratory illnesses in the vaccine group warrants expanded safety studies.
ClinicalTrials.gov NCT00767416.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUND:Influenza B viruses from 2 lineages cocirculate annually. Because the single B strain contained in trivalent vaccines may not match the major circulating strain, adding a second B virus ...could enhance protection. This study compared the safety and immunogenicity of an investigational quadrivalent Ann Arbor strain live attenuated influenza vaccine (Q/LAIV) with that of 2 trivalent vaccines (T/LAIV), each containing a B strain from a different lineage.
METHODS:This randomized, double-blind study was designed to demonstrate the immunologic noninferiority of Q/LAIV compared with T/LAIV in children 2–17 years of age by comparing postdose geometric mean titers of hemagglutination inhibition antibodies. Children were randomized 3:1:1 to receive Q/LAIV or 1 of 2 T/LAIV vaccines. Those subjects who were 9–17 years of age received 1 dose, and those 2–8 years of age received 2 doses 1 month apart. Serum immune responses were evaluated 1 month after dose 1 (dose 2 for influenza vaccine–naive subjects aged 2–8 years).
RESULTS:Q/LAIV was noninferior to T/LAIVupper bounds for all four 95% confidence intervals for the postdose geometric mean titer ratios (T/LAIV divided by Q/LAIV) were ≤1.5, the predefined noninferiority margin. The overall seroresponse rates (4-fold rise) were comparable between treatment groups. Safety events were comparable, except that fever was more common after dose 1 in Q/LAIV subjects (5.1%) than in T/LAIV subjects (3.1%) 2–8 years of age.
CONCLUSIONS:The immunogenicity of Q/LAIV was noninferior to that of T/LAIV in children aged 2–17 years; safety was also comparable. Q/LAIV may broaden the protection against influenza B strains provided by current trivalent influenza vaccines.
The safety, tolerability, and immunogenicity of a monovalent intranasal 2009 A/H1N1 live attenuated influenza vaccine (LAIV) were evaluated in children and adults.
Two randomized, double-blind, ...placebo-controlled studies were completed in children (2-17 y) and adults (18-49 y). Subjects were assigned 4:1 to receive 2 doses of H1N1 LAIV or placebo 28 days apart. The primary safety endpoint was fever ≥38.3°C during days 1-8 after the first dose; the primary immunogenicity endpoint was the proportion of subjects experiencing a postdose seroresponse. Solicited symptoms and adverse events were recorded for 14 days after each dose and safety data were collected for 180 days post-final dose. In total, 326 children (H1N1 LAIV, n = 261; placebo, n = 65) and 300 adults (H1N1 LAIV, n = 240; placebo, n = 60) were enrolled. After dose 1, fever ≥38.3°C occurred in 4 (1.5%) pediatric vaccine recipients and 1 (1.5%) placebo recipient (rate difference, 0%; 95% CI: -6.4%, 3.1%). No adults experienced fever following dose 1. Seroresponse rates in children (H1N1 LAIV vs. placebo) were 11.1% vs. 6.3% after dose 1 (rate difference, 4.8%; 95% CI: -9.6%, 13.8%) and 32.0% vs. 14.5% after dose 2 (rate difference, 17.5%; 95% CI: 5.5%, 27.1%). Seroresponse rates in adults were 6.1% vs. 0% (rate difference, 6.1%; 95% CI: -5.6%, 12.6%) and 14.9% vs. 5.6% (rate difference, 9.3%; 95% CI: -0.8%, 16.3%) after dose 1 and dose 2, respectively. Solicited symptoms after dose 1 (H1N1 LAIV vs. placebo) occurred in 37.5% vs. 32.3% of children and 41.7% vs. 31.7% of adults. Solicited symptoms occurred less frequently after dose 2 in adults and children. No vaccine-related serious adverse events occurred.
In subjects aged 2 to 49 years, two doses of H1N1 LAIV have a safety and immunogenicity profile similar to other previously studied and efficacious formulations of seasonal trivalent LAIV.
ClinicalTrials.gov NCT00946101, NCT00945893.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Highly purified subunit vaccines require potent adjuvants in order to elicit optimal immune responses. In a previous phase I trial, an alum formulation of ICC-1132, a malaria vaccine candidate ...comprising hepatitis B core (HBc) virus-like particle containing Plasmodium falciparum circumsporozoite (CS) protein epitopes, was shown to elicit Plasmodium falciparum-specific antibody and cellular responses. The present study was designed as a single-blind, escalating-dose phase I trial to evaluate the safety and immunogenicity of single intramuscular doses of ICC-1132 formulated in the more potent water-in-oil adjuvant Montanide ISA 720 (ICC-1132/ISA 720). The vaccine was safe and well tolerated, with transient injection site pain as the most frequent complaint. All vaccinees that received either 20 microg or 50 microg of ICC-1132/ISA 720 developed antiimmunogen and anti-HBc antibodies. The majority of volunteers in these two groups developed sporozoite-specific antibodies, predominantly of opsonizing immunoglobulin G subtypes. Peak titers and persistence of parasite-specific antibody following a single injection of the ISA 720 formulated vaccine were comparable to those obtained following two to three immunizations with alum-adsorbed ICC-1132. Peripheral blood mononuclear cells of ICC-1132/ISA 720 vaccinees proliferated and released cytokines (interleukin 2 and gamma interferon) when stimulated with recombinant P. falciparum CS protein, and CS-specific CD4⁺ T-cell lines were established from volunteers with high levels of antibodies to the repeat region. The promising results obtained with a single dose of ICC-1132 formulated in Montanide ISA 720 encourage further clinical development of this malaria vaccine candidate.
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