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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.

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.

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.

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-[mu]g or 25-[mu]g 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-[mu]g and 25-[mu]g NVX-CoV2373 induced robust immune responses in younger and older participants. For the 2-dose regimen of 5 [mu]g, 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-[mu]g NVX-CoV2373 is highly immunogenic and well tolerated in younger adults. In addition, in older adults, the 2-dose regimen of 5 [mu]g was also well tolerated and showed sufficient immunogenicity to support its use in late-phase efficacy studies.

With the recent rise in cases of highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b infection in humans and animals, there is an associated increase in the risk of human-to-human transmission. In this study, we characterize a recombinant A(H5N1) A/American Wigeon/South Carolina/22/000345-001/2021 (A/AW/SC/2021) clade 2.3.4.4b vaccine. Purified recombinant A/AW/SC/2021 HA trimers formulated with Matrix-M ® adjuvant, saponin-cholesterol-phospholipid combination arranged in cage-like particles, are found to non-covalently anchor to the vertices of the Matrix-M and form A(H5N1) HA – Matrix-M nanoparticles (H5-MNPs). In naïve female mice, two intranasal (IN) or intramuscular (IM) doses of A/AW/SC/2021 H5-MNP vaccine induces robust antibody- and cell-mediated immune responses, including neutralizing antibodies against A(H5N1). In non-human primates (NHPs) primed with seasonal influenza vaccine, a single IM or IN dose of the A/AW/SC/2021 H5-MNP vaccine induces geometric mean serum A(H5N1) clade 2.3.4.4b pseudovirus neutralizing titers of 1:1160 and 1:54, respectively; above the generally accepted seroconverting neutralizing titer of 1:40. Immunization with H5-MNP vaccine induces antibody responses against conserved epitopes in the A(H5N1) HA stem, vestigial esterase subdomain, and receptor binding site. This A(H5N1) H5-MNP IN and IM vaccine is immunogenic in female rodents and NHPs as a potential A(H5N1) pandemic single-dose vaccine. The rise in highly pathogenic avian influenza cases elevates the risk of human-to-human transmission. Here, the authors develop an adjuvanted protein-based vaccine that elicits robust antibody- and cell-mediated immune responses in mice and non-human primates, suggesting its potential to induce protective immunity in humans.

► 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. Trivalent seasonal influenza vaccines contain 2 A strains and 1 B strain. B strains of 2 antigenically distinct lineages, Yamagata and Victoria, have been co-circulating annually, and the B strain included in vaccines often has not been a lineage match to the major circulating strain. Thus, a vaccine containing B strains from both lineages could broaden protection against influenza. Quadrivalent live attenuated influenza vaccine (Q/LAIV) is an investigational 4-strain formulation of LAIV that contains 2 A strains, A/H1N1 and A/H3N2, and 2 B strains, 1 from each lineage. A randomized, double-blind, active-controlled study of Q/LAIV was conducted in 1800 adults aged 18–49 years to compare the immunogenicity and safety of Q/LAIV to trivalent LAIV (T/LAIV). Subjects were randomized 4:1:1 to receive an intranasal dose of Q/LAIV (n=1200) or 1 of 2 matching T/LAIV vaccines, each containing 1 of the B strains included in Q/LAIV (n=600 total). The primary endpoint was the comparison of the post-vaccination strain-specific geometric mean titers (GMT) of hemagglutination inhibition antibody in Q/LAIV recipients to those in T/LAIV recipients, with immunologic noninferiority of Q/LAIV to be demonstrated if the upper bound of the 2-sided 95% confidence interval (CI) for the ratio of the GMTs [T/LAIV divided by Q/LAIV] was ≤1.5 for all strains. Q/LAIV met the criteria for noninferiority: the ratios of the GMTs for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria strains were 1.09 (95% CI, 1.01–1.18), 1.05 (95% CI, 0.96–1.14), 1.10 (95% CI, 0.97–1.25), and 0.92 (95% CI, 0.82–1.03), respectively. Solicited symptoms and adverse events were similar in the Q/LAIV and T/LAIV arms. Q/LAIV may confer increased protection against influenza by targeting B strains from both lineages.

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.

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.

A randomized, phase 2 trial compared the NVX-CoV2373 nanoparticle vaccine with placebo in participants in South Africa, including 30% who were seropositive at baseline. Overall vaccine efficacy was 49.4%, with the B.1.351 variant identified in more than 90% of isolates.

NVX-CoV2373 is a vaccine containing a full-length stabilized recombinant spike protein trimer that is administered in two doses 3 weeks apart along with a saponin-based adjuvant. In a randomized trial, approximately 20,000 participants received the vaccine and 10,000 a placebo. Vaccine efficacy against infection was 90%, and reactogenicity was similar to that of other Covid-19 vaccines.