A single intranasal dose of a live-attenuated parainfluenza virus-vectored SARS-CoV-2 vaccine is protective in hamsters

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 118; no. 50; pp. 1 - 11
• Main Authors: Liu, Xueqiao, Luongo, Cindy, Matsuokaa, Yumiko, Park, Hong-Su, Santos, Celia, Yang, Lijuan, Moore, Ian N., Afroz, Sharmin, Johnson, Reed F., Lafont, Bernard A. P., Martens, Craig, Best, Sonja M., Munster, Vincent J., Hollý, Jaroslav, Yewdell, Jonathan W., Le Nouën, Cyril, Munir, Shirin, Buchholz, Ursula J.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 14.12.2021
• Subjects: Administration, Intranasal; Animals; Antibodies; Antibodies, Viral - blood; Antigens; Biological Sciences; Children; Coronaviruses; COVID-19; COVID-19 - prevention & control; COVID-19 vaccines; COVID-19 Vaccines - administration & dosage; COVID-19 Vaccines - genetics; COVID-19 Vaccines - immunology; Cricetinae; Genetic Vectors; Hamsters; Immunization; Immunoglobulin A; Immunoglobulin G; Infants; Lungs; Neutralization; Neutralizing; Parainfluenza; Parainfluenza Virus 3, Bovine - genetics; Parainfluenza Virus 3, Human - genetics; Protein folding; Proteins; Replication; Respiratory tract; SARS-CoV-2 - immunology; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - immunology; Spike protein; Tissue culture; Vaccines; Vaccines, Attenuated - administration & dosage; Vaccines, Attenuated - genetics; Vaccines, Attenuated - immunology; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - genetics; Vaccines, Synthetic - immunology; Viruses; Weight loss; COVID-19; SARS-CoV-2; vaccine vector; intranasal immunization; parainfluenza virus vaccines
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.2109744118

Single-dose vaccines with the ability to restrict SARS-CoV-2 replication in the respiratory tract are needed for all age groups, aiding efforts toward control of COVID-19. We developed a live intranasal vector vaccine for infants and children against COVID-19 based on replication-competent chimeric bovine/human parainfluenza virus type 3 (B/HPIV3) that express the native (S) or prefusion-stabilized (S-2P) SARS-CoV-2 S spike protein, the major protective and neutralization antigen of SARS-CoV-2. B/HPIV3/S and B/HPIV3/S-2P replicated as efficiently as B/HPIV3 in vitro and stably expressed SARS-CoV-2 S. Prefusion stabilization increased S expression by B/HPIV3 in vitro. In hamsters, a single intranasal dose of B/HPIV3/S-2P induced significantly higher titers compared to B/HPIV3/S of serum SARS-CoV-2–neutralizing antibodies (12-fold higher), serum IgA and IgG to SARS-CoV-2 S protein (5-fold and 13-fold), and IgG to the receptor binding domain (10-fold). Antibodies exhibited broad neutralizing activity against SARS-CoV-2 of lineages A, B.1.1.7, and B.1.351. Four weeks after immunization, hamsters were challenged intranasally with 104.5 50% tissue-culture infectious-dose (TCID50) of SARS-CoV-2. In B/HPIV3 empty vector-immunized hamsters, SARS-CoV-2 replicated to mean titers of 106.6 TCID50/g in lungs and 10⁷ TCID50/g in nasal tissues and induced moderate weight loss. In B/HPIV3/S-immunized hamsters, SARS-CoV-2 challenge virus was reduced 20-fold in nasal tissues and undetectable in lungs. In B/HPIV3/S-2P–immunized hamsters, infectious challenge virus was undetectable in nasal tissues and lungs; B/HPIV3/S and B/HPIV3/S-2P completely protected against weight loss after SARS-CoV-2 challenge. B/HPIV3/S-2P is a promising vaccine candidate to protect infants and young children against HPIV3 and SARS-CoV-2.