More than 800 children 0 to 11 years of age have died from COVID-19 in the US (https://covid.cdc.gov/covid-data-tracker/#demographics, accessed on April 22, 2022), and during the fall/winter season COVID-19 wave of 2021/2022, children accounted for over 25% of US instances (Gerber and Offit, 2021). challenge, SARS-CoV-2 replication was undetectable in airways and lung cells of immunized macaques. B/HPIV3/S-6P will become evaluated clinically as pediatric intranasal SARS-CoV-2/parainfluenza computer virus type 3 vaccine. One-Sentence Summary: Intranasal parainfluenza virus-vectored COVID-19 vaccine induces anti-S antibodies, T-cell memory space and safety in macaques. INTRODUCTION Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects and causes disease in all age groups. Although COVID-19 is generally milder in young children than in adults, thousands of children have been hospitalized due to COVID-19 in the US only, including about one-third without preexisting medical conditions (Funk et al., 2022; Rankin et al., 2021). More than 800 children 0 to 11 years of age have died from COVID-19 in the US (https://covid.cdc.gov/covid-data-tracker/#demographics, accessed on April 22, 2022), and during the fall/winter season COVID-19 wave of 2021/2022, children accounted for over 25% of US instances (Gerber and Offit, 2021). In rare cases (~0.03% of infected children), COVID-19 can cause a multisystem inflammatory syndrome in children [MIS-C; (Riphagen et al., 2020; Verdoni et al., 2020)], arising within on the subject of 4 weeks after SARS-CoV-2 exposure. While mRNA-based vaccines are available for children 5 years of age and older, to date, no vaccine has been authorized or recommended for children under 5 years of age. Furthermore, interim results from an ongoing Phase 1/2/3 clinical study suggested that a third 3-g dose of the BNT162b2 mRNA vaccine may be needed to elicit strong immune reactions in children 2 to 5 years of age; accordingly, a 3-dose regimen is being evaluated in children 6 months to 5 years of age (“type”:”clinical-trial”,”attrs”:”text”:”NCT04816643″,”term_id”:”NCT04816643″NCT04816643). One limitation of the current mRNA and additional injectable SARS-CoV-2 vaccines is definitely that they do not directly stimulate immunity in the respiratory tract, the major site of SARS-CoV-2 access, replication, disease, and egress (DiPiazza et al., 2021). Consequently, it is important to evaluate additional vaccine methods that are suitable for pediatric use and stimulate both mucosal and systemic immunity. Ideally, a vaccine should be Deltasonamide 2 (TFA) effective at a single dose, and could become administered topically to the respiratory tract to induce strong systemic and respiratory mucosal immunity that restricts SARS-CoV-2 illness and shedding. Here, we describe the pre-clinical evaluation of the security, immunogenicity, and Deltasonamide 2 (TFA) protecting efficacy of a live intranasal SARS-CoV-2 vaccine candidate, B/HPIV3/S-6P, in rhesus macaques. B/HPIV3/S-6P consists of a live-attenuated chimeric bovine/human being parainfluenza computer virus type-3 (B/HPIV3) that was altered to express the SARS-CoV-2 S-protein trimer stabilized in the prefusion form. The B/HPIV3 vector originally was developed like a pediatric vaccine candidate against human being PIV3 (HPIV3), a single-stranded negative-sense RNA computer virus which is an important cause of respiratory illness, especially in babies and young children under 5 years of age Deltasonamide 2 (TFA) (DeGroote et al., 2020; Howard et al., 2021). Previously, B/HPIV3 was well-tolerated inside a Phase 1 study in babies and young children (Karron et al., 2012). B/HPIV3 also has been used to express the fusion (F) glycoprotein of another human being respiratory pathogen, human being respiratory syncytial computer virus (RSV), providing a bivalent HPIV3/RSV vaccine candidate which was well-tolerated in children 2 months of age [(Bernstein et al., 2012), Clinicaltrials.gov “type”:”clinical-trial”,”attrs”:”text”:”NCT00686075″,”term_id”:”NCT00686075″NCT00686075]. We recently reported that B/HPIV3 expressing a stabilized Deltasonamide 2 (TFA) prefusion form of S efficiently safeguarded hamsters against illness having a vaccine antigen-matched SARS-CoV-2 isolate, avoiding weight loss, lung swelling and efficiently reducing SARS-CoV-2 replication in the top and lower respiratory tract (Liu et al., 2021). In the present study, we evaluated the security and effectiveness of a single intranasal/intratracheal (IN/IT) dose of B/HPIV3/S-6P in rhesus macaques (RM). Immunogenicity evaluations included S-specific mucosal and systemic antibody and T-cell reactions as well as neutralizing antibody reactions to the vaccine-matched SARS-CoV-2 strain and four major variants of concern. In addition, we assessed the protecting effectiveness of B/HPIV3/S-6P against SARS-CoV-2 challenge prior to improving this Rabbit Polyclonal to ARSA candidate to a Phase 1.