Assessment of safety and intranasal neutralizing antibodies of HPMC-based human anti-SARS-CoV-2 IgG1 nasal spray in healthy volunteers.

An HPMC-based nasal spray solution containing human IgG1 antibodies against SARS-CoV-2 (nasal antibody spray or NAS) was developed to strengthen COVID-19 management. NAS exhibited potent broadly neutralizing activities against SARS-CoV-2 with PVNT50 values ranging from 0.0035 to 3.1997 µg/ml for the following variants of concern (ranked from lowest to highest): Alpha, Beta, Gamma, ancestral, Delta, Omicron BA.1, BA.2, BA.4/5, and BA.2.75. Biocompatibility assessment showed no potential biological risks. Intranasal NAS administration in rats showed no circulatory presence of human IgG1 anti-SARS-CoV-2 antibodies within 120 h. A double-blind, randomized, placebo-controlled trial (NCT05358873) was conducted on 36 healthy volunteers who received either NAS or a normal saline nasal spray. Safety of the thrice-daily intranasal administration for 7 days was assessed using nasal sinuscopy, adverse event recording, and self-reporting questionnaires. NAS was well tolerated, with no significant adverse effects during the 14 days of the study. The SARS-CoV-2 neutralizing antibodies were detected based on the signal inhibition percent (SIP) in nasal fluids pre- and post-administration using a SARS-CoV-2 surrogate virus neutralization test. SIP values in nasal fluids collected immediately or 6 h after NAS application were significantly increased from baseline for all three variants tested, including ancestral, Delta, and Omicron BA.2. In conclusion, NAS was safe for intranasal use in humans to increase neutralizing antibodies in nasal fluids that lasted at least 6 h.

Immunogenicity and reactogenicity against the SARS-CoV-2 variants following heterologous primary series involving CoronaVac, ChAdox1 nCov-19 and BNT162b2 plus BNT162b2 booster vaccination: An open-label randomized study in healthy Thai adults.

We evaluated the immunogenicity and reactogenicity of heterologous COVID-19 primary schedules involving BNT162b2 (Pfizer-BioNTech), ChAdOx1 nCoV-19 (AstraZeneca) and CoronaVac (Sinovac) in healthy adults, as well as booster response to BNT162b2 following heterologous CoronaVac and ChAdOx1 nCoV-19 regimens. Participants were randomized to one of seven groups that received two-dose homologous BNT162b2 or heterologous combinations of CoronaVac, ChAdOx1 nCoV-19 and BNT162b2, with 4 weeks interval. A total of 210 participants were enrolled, 30 in each group. Median age of participants was 38 (19-60) years, and 108/210 (51.43%) were female. Overall adverse events after the second dose were mild to moderate. We found that groups that received BNT162b2 as second dose induced the highest anti-receptor binding domain IgG response against the ancestral strain [BNT162b2: geometric mean concentration (GMC) 2133-2249 BAU/mL; ChAdOx1 nCoV-19: 851-1201; CoronaVac: 137-225 BAU/mL], neutralizing antibodies (NAb) against Beta and Delta, and interferon gamma response. All groups induced low to negligible NAb against Omicron after second dose. A BNT162b2 booster (third dose) following heterologous CoronaVac and ChAdOx1 nCoV-19 regimens induced >140-fold increase in NAb titers against Omicron. Our findings indicate that heterologous regimens using BNT162b2 as the second dose may be an alternative schedule to maximize immune response. While heterologous two-dose schedules induced low NAb against Omicron, the use of an mRNA vaccine booster dose substantially increased the Omicron response. These findings are relevant for low-income countries considering heterologous primary and booster COVID-19 vaccine schedules.