ABSTRACT
Successful COVID-19 prevention requires additional measures beyond vaccination, social distancing, and masking. A nasal spray solution containing human IgG1 antibodies against SARS-CoV-2 (COVITRAP) was developed to strengthen other COVID-19 preventive arsenals. Here, we evaluated its pseudovirus neutralization potencies, preclinical and clinical safety profiles, and intranasal SARS-CoV-2 inhibitory effects in healthy volunteers (NCT05358873). COVITRAP exhibited broadly potent neutralizing activities against SARS-CoV-2 with PVNT50 values ranging from 0.0035 to 3.1997 g/ml for the following variants of concern (ranked from lowest to highest): Alpha, Beta, Gamma, Ancestral, Delta, Omicron BA.1, Omicron BA.2, Omicron BA.4/5, and Omicron BA.2.75. It demonstrated satisfactory preclinical safety profiles based on evaluations of in vitro cytotoxicity, skin sensitization, intracutaneous reactivity, and systemic toxicity. Its intranasal administration in rats did not yield any detected circulatory levels of the human IgG1 anti-SARS-CoV-2 antibodies at any time point during the 120 hours of follow-up. A double-blind, randomized, placebo-controlled trial (RCT) was conducted on 36 healthy volunteers who received either COVITRAP or a normal saline nasal spray at a 3:1 ratio. Safety of the thrice-daily intranasal administration for 7 days was assessed using nasal sinuscopy, adverse event recording, and self-reporting questionnaires. COVITRAP was well tolerated, with no significant adverse effects in healthy volunteers for the entire 14 days of the study. The intranasal SARS-CoV-2 inhibitory effects of COVITRAP were evaluated in nasal fluids taken from volunteers pre- and post-administration using a SARS-CoV-2 surrogate virus neutralization test. SARS-CoV-2 inhibitory effects in nasal fluids collected immediately or six hours after COVITRAP application were significantly increased from baseline for all three variants tested, including Ancestral, Delta, and Omicron BA.2. In conclusion, COVITRAP was safe for intranasal use in humans to provide SARS-CoV-2 inhibitory effects in nasal fluids that lasted at least six hours. Therefore, COVITRAP can be considered an integral instrument for COVID-19 prevention.
ABSTRACT
The CoronaVac (Sinovac Biotech) and ChAdOx1(Oxford-AstraZeneca) are two widely used COVID-19 vaccines. We examined the immunogenicity of four COVID-19 booster vaccine: BBIBP-CorV (Sinopharm Biotech), ChAdOx1, 30g-BNT162b2 and 15g-BNT162b2 (Pfizer-BioNTech), in healthy adults who received a two-dose CoronaVac or ChAdOx1 8-12 weeks earlier. Among the 352 participants (179 CoronaVac and 173 ChAdOx1 participants), 285 (81%) were female, and median age was 39(IQR: 31-47) years. 98%(175/179) and 99%(172/173) of Coronavac and ChAdOx1 participants remained seropositive at baseline. Two weeks post-booster, both 30g- and 15g-BNT162b2 induced the highest anti-RBD IgG concentration (BAU/mL); Coronavac-prime: 30g-BNT162b2, 5152.2(95%CI 4491.7-5909.8); 15g-BNT162b2, 3981.1(3397.2-4665.4); ChAdOx1, 1358.0(1141.8-1615.1); BBIBP-CorV, 154.6(92.11-259.47); ChAdOx1-prime: 30g-BNT162b2, 2363.8(2005.6-2786.1; 15g-BNT162b2, 1961.9(1624.6-2369.1); ChAdOx1, 246.4(199.6-304.2); BBIBP-CorV, 128.1(93.5-175.4). Similarly, both 30g- and 15g-BNT162b2 boosting induced the highest neutralizing antibodies (nAb) titres against all variants and highest T-cell response evaluated by interferon gamma released asssays. While all BNT162b2 or heterologous ChAdOx1-boosted participants had nAb against Omicron, these were <50% for BBIBP-CorV and 75% for homologous ChAdOx1-boosted participants. There was significant decrease in nAb (>4-fold) 16-20 weeks post booster. Heterologous boosting with BNT162b2 following CoronaVac or ChAdOx1 primary series is most immunogenic. A lower dose BNT162b2 may be considered as booster in settings with limited vaccine supply.
ABSTRACT
BackgroundResponding to SARS-CoV-2 Delta variants escaped the vaccine-induced immunity and waning immunity from the inactivated whole virus vaccine, Thailand recently proposed a heterologous inactivated whole virus vaccine (CoronaVac) viral vector vaccine (ChAdOx1 nCoV-19) prime-boost vaccine regimen(I/V). This study aims to evaluate the immunogenicity and adverse events of this regimen by comparison with homologous CoronaVac, ChAdOx1 nCoV-19, and convalescent serum. MethodImmunogenicity was evaluated by the level of IgG antibodies against the receptor-binding domain of the SARS-CoV-2 spike protein (S1 subunit) (anti-S RBD). At 2 weeks following the second dosage, a selection of random samples was tested for plaque reduction neutralisation (PRNT) and Pseudotype-Based Microneutralization test (PVNT) against SARS-CoV-2 variants of concern (VOCs). The safety profile of heterologous CoronaVac-ChAdOx1 nCoV-19 prime-boost vaccine regimen was described by interviewing at the 1-month visit. ResultBetween April to August 2021,426 participants were included in the study, with 155 obtaining CoronaVac-ChAdOx1 nCoV-19(I/V),32 obtaining homologous CoronaVac(I/I),47 obtaining homologous ChAdOx1 nCoV-19(V/V),169 with history covid-19 infection. Geometric mean titers (GMTs) of anti-S RBD level in the I/V group compare 2wks and 4 wks (873.9 vs 639,p=0.00114).At 4 wks, GMTs of anti-S RBD level in I/V group was 639, 95% CI 63-726,and natural infection group 177.3, 95% CI 42-221, and V/V group 211.1, 95% CI 77-152, and I/I group 108.2, 95% CI 77-152; all p<0.001).At 2 wks, The GMTs of 50%PRNT of 19 sampling from the I/V group is 434.5, 95% CI 326-579, against wild type and 80.4, 95% CI 56-115, against alpha and 67.4, 95% CI 48-95, against delta and 19.8, 95% CI 14-30, against beta; all p<0.001. At 2 wks, The GMTs of 50%PVNT of 15 sampling from the I/V group is 597.8, 95% CI 368-970, against wild type and 163.9, 95% CI 89-301, against alpha and 157.7, 95% CI 66-378, against delta. The AEs in the I/V schedule were well tolerated and generally unremarkable. ConclusionThe I/V vaccination is a mixed regimen that induced higher immunogenicity and shall be considered for responding to Delta Variants when only inactivated whole virus vaccine and viral vector vaccine was available.
