Immunogenicity and durability against Omicron BA.1, BA.2 and BA.4/5 variants at 3 to 4 months after a heterologous COVID-19 booster vaccine in healthy adults with a two-doses CoronaVac vaccination

ObjectivesSeveral countries have authorized a booster vaccine campaign to combat the spread of COVID-19. Data on persistence of booster vaccine-induced immunity against new Omicron subvariants are still limited. Therefore, our study aimed to determine the serological immune response of COVID-19 booster after CoronaVac-priming. MethodsA total of 187 CoronaVac-primed participants were enrolled and received an inactivated (BBIBP), viral vector (AZD1222) or mRNA vaccine (full-/half-dose BNT162B2, full-/half-dose mRNA-1273) as a booster dose. The persistence of humoral immunity both binding and neutralizing antibodies against wild-type and Omicron was determined on day 90- 120 after booster. ResultsA waning of total RBD immunoglobulin (Ig) levels, anti-RBD IgG, and neutralizing antibodies against Omicron BA.1, BA.2, and BA.4/5 variants was observed 90-120 days after booster vaccination. Participants who received mRNA-1273 had the highest persistence of the immunogenicity response, followed by BNT162b2, AZD1222, and BBIBP-CorV. The responses between full and half doses of mRNA-1273 were comparable. The percentage reduction of binding antibody ranged from 50% to 75% among all booster vaccine. ConclusionsThe antibody response substantially waned after 90-120 days post-booster dose. The heterologous mRNA and the viral vector booster demonstrated higher detectable rate of humoral immune responses against the Omicron variant compared to the inactivated BBIBP booster. Nevertheless, an additional fourth dose is recommended to maintain immune response against infection. HighlightsO_LIThe persistence of antibody responses is different among three vaccine platforms. C_LIO_LIHighly remained antibody levels were observed with the mRNA and viral vector booster. C_LIO_LIThe half-dose mRNA-1273 can be used interchangeably with the full-dose mRNA-1273. C_LIO_LIThe neutralizing activity against BA.5 was lower than wild type and BA.2 subvariant. C_LIO_LIA fourth dose is recommended for individuals who received an inactivated booster. C_LI

Safety and Immunogenicity of Intradermal Administration of Fractional Dose CoronaVac(R), ChAdOx1 nCoV-19 and BNT162b2 as Primary Series Vaccination

There is a limited supply of COVID-19 vaccines, with less than 20% of eligible populations in low-income countries having received one dose. Intradermal delivery of fractional dose vaccines is one way to improve global vaccine access, but no studies have reported data on intradermal delivery of COVID-19 primary series vaccination. We conducted a pilot study to examine the safety and immunogenicity of three intradermal primary series regimens - heterologous regimen of CoronaVac and ChAdOx1 (CoronaVac-ChAdOx1), homologous regimen of ChAdOx1 (ChAdOx1-ChAdOx1), and homologous regimen of BNT162b2 (BNT162b2-BNT162b2). Each dose was 1/5th or 1/6th of the standard dose. Two additional exploratory arms of intradermal vaccination for the second dose following an intramuscular first dose of ChAdOx1 and BNT162b2 were included. Intradermal vaccination was found to be immunogenic and safe. The antibody responses generated by the intradermal primary series were highest in the BNT162b2 arms. The anti-receptor binding domain (anti-RBD) IgG concentration following fractional dose intradermal vaccination was similar to that of standard dose intramuscular vaccination of the same regimen, except for BNT162b2. The BNT162b2 intradermal series generated a lower antibody concentration than the reference intramuscular series, despite generating the highest antibody concentration of all three intradermal primary series regimens. Neutralizing antibody responses against the SARS-CoV-2 ancestral strain were consistent with what was observed for anti-RBD IgG, with lower titers for SARS-CoV-2 variants. The FRNT50 titers were lowest against the omicron variant, being undetectable (GMT[≤]10) in about a quarter of study participants. T-cell responses against spike- and nucleocapsid-membrane-open reading frame proteins were also detected following intradermal vaccination. Adverse effects following intradermal vaccination were generally comparable with post-intramuscular vaccination effects. Taken together, our data suggest that intradermal vaccination using 1/5th or 1/6th of standard COVID-19 intramuscular vaccination dosing generates similar immune responses with tendency of lower systemic adverse reactions than intramuscular vaccination. Our findings have implications in settings where COVID-19 vaccines are in shortage.

Strong correlations between the binding antibodies against wild type and neutralizing antibodies against omicron BA.1 and BA.2 variants of SARS-CoV-2 in individuals following booster (third dose) vaccination

This study examined the neutralizing activity and receptor binding domain (RBD) antibody levels against wild-type and omicron BA.1 and BA.2 variants in individuals who received three doses of COVID-19 vaccination. The relationship between the SARS-CoV-2 RBD antibody against wild-type and live virus neutralizing antibody titers against omicron BA.1 and BA.2 variants was examined. In total, 310 sera samples from individuals after booster vaccination (third dose) vaccination were tested for specific IgG wild-type SARS-CoV-2 RBD and the omicron BA.1 surrogate virus neutralization test (sVNT). The live virus neutralization assay against omicron BA.1 and BA.2 was performed using the foci-reduction neutralization test (FRNT50). The anti-RBD IgG strongly correlated with FRNT50 titers against BA.1 and BA.2. Non-linear regression showed that anti-RBD IgG with [≥]148 BAU/mL and [≥]138 BAU/mL were related to detectable FRNT50 titers ([≥]1:20) against BA.1 and BA.2, respectively. A moderate correlation was observed between the sVNT and FRNT50 titers. At detectable FRNT50 titers ([≥]1:20), the predicted sVNT for BA.1 and BA.2 were [≥]10.57% and [≥]11.52%, respectively. The study identified anti-RBD IgG and sVNT levels that predict detectable neutralizing antibodies against omicron variants. Assessment and monitoring of protective immunity support vaccine policies and will help identify optimal timing for booster vaccination.

Persistence of immunity against omicron BA.1 and BA.2 following homologous and heterologous COVID-19 booster vaccines in healthy adults after a two-doses AZD1222 vaccination

ObjectivesThe SARS-CoV-2 Omicron variant presents numerous mutations potentially able to evade neutralizing antibodies (NAbs) elicited by COVID-19 vaccines. Therefore, this study aimed to provide evidence on a heterologous booster strategy to overcome the waning immunity against Omicron variants. MethodsParticipants who completed Oxford/AstraZeneca (hereafter AZD1222) for 5-7 months were enrolled. The reactogenicity and persistence of immunogenicity in both humoral and cellular response after a homologous or heterologous booster with the AZD1222 and mRNA vaccines (BNT162B2, full or half-dose mRNA-1273) administered six months after primary vaccination were determined. ResultsTotal 229 individuals enrolled, a waning of immunity was observed 5-7 months after the AZD1222-primed. Total RBD immunoglobulin (Ig) levels, anti-RBD IgG and focus reduction neutralization test against Omicron BA.1 and BA.2 and T cell response peaked 14-28 days after booster vaccination. Both the full and half dose of mRNA-1273 induced the highest response, followed by BNT162b2 and AZD1222. At 90 days, the persistence of immunogenicity was observed among all mRNA-boosted individuals. Adverse events were acceptable and well tolerated for all vaccines. ConclusionsA heterologous mRNA booster provided a significantly superior boost of binding and NAbs levels against the Omicron variant compared to a homologous booster in individuals with AZD1222-primed vaccinations.

Effects of boosted mRNA and adenoviral-vectored vaccines on immune responses to omicron BA.1 and BA.2 following the heterologous CoronaVac/AZD1222 vaccination

BackgroundThe coronavirus 2019 omicron variant has surged rapidly and raises concerns about immune evasion because it harbors mutations even in individuals with complete vaccination. Here, we examine the capability of the booster vaccination to induce neutralizing antibodies (NAbs) against omicron (BA.1 and BA.2) and T-cell responses. MethodsA total of 167 participants primed with heterologous CoronaVac/AZD1222 were enrolled to receive AZD1222, BNT162b2, or mRNA-1273 as a booster dose. Reactogenicity was recorded. Binding antibody, neutralizing antibody (NAb) titers against omicron BA.1 and BA.2, and total interferon gamma (IFN-{gamma}) post-booster responses were measured. ResultsA substantial loss in neutralizing potency to omicron variant was found at 4 to 5 months after receiving the heterologous CoronaVac/AZD1222. Following booster vaccination, a significant increase in binding antibodies and neutralizing activities toward delta and omicron variants was observed. Neutralization to omicron BA.1 and BA.2 were comparable, showing the highest titers after boosted mRNA-1273 followed by BNT162b2 and AZD1222. Notably, boosted individuals with mRNA vaccines could induce T cell response. Reactogenicity was mild to moderate without serious adverse events. ConclusionsOur findings highlight that the booster vaccination could overcome immunity wanes and provide adequate NAbs coverage against omicron BA.1 and BA.2.

Comparison of the reactogenicity and immunogenicity of a reduced and standard booster dose of the mRNA COVID-19 vaccine in healthy adults after two doses of inactivated vaccine.

The coronavirus disease 2019 (COVID-19) pandemic has been a serious healthcare problem worldwide since December 2019. The third dose of heterologous vaccine was recently approved by World Health Organization. The present study compared the reactogenicity and immunogenicity of the reduced and standard third booster dose of the BNT162b2 and mRNA-1273 vaccine in adults who previously received the two-dose CoronaVac vaccine. Results showed that headache, joint pain, and diarrhea were more frequent in the 15 g-than the 30 g-BNT162b2 groups, whereas joint pain and chilling were more frequent in the 100 g-than the 50 g-mRNA-1273 groups. No significant differences in immunogenicity were detected. These findings demonstrate that the reduced dose of the mRNA vaccines elicited antibody responses against the SARS-CoV-2 delta and omicron variants that were comparable to the standard dose. The reduced dose could be used to increase vaccine coverage in situations of limited global vaccine supply. HighlightsO_LIThe 15 g- and 30 g-BNT162b2, and 50 g- and 100 g-mRNA-1273 booster doses were compared C_LIO_LIBooster vaccination with the mRNA vaccine elicits high Ig and IgG anti-RBD in CoronaVac-vaccinated adults C_LIO_LINo differences were observed in antibody responses after the reduced or standard booster dose of the mRNA vaccine in CoronaVac-vaccinated adults C_LIO_LINeutralizing antibodies against the delta and omicron variants were significantly higher after the booster dose C_LIO_LINeutralizing antibody titers were lower against the omicron variant than the delta variant in all vaccinated adults C_LI

Neutralizing Activities against the Omicron Variant after a Heterologous Booster in Healthy Adults Receiving Two Doses of CoronaVac Vaccination

BackgroundThe use of an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (CoronaVac) against SARS-CoV-2 is implemented worldwide. However, waning immunity and breakthrough infections have been observed. Therefore, we hypothesized that the heterologous booster might improve the protection against the delta and omicron variants. MethodsA total of 224 individuals who completed the two-dose CoronaVac for six months were included. We studied reactogenicity and immunogenicity following a heterologous booster with the inactivated vaccine (BBIBP), the viral vector vaccine (AZD1222), and the mRNA vaccine (both BNT162B2 and mRNA-1273). We also determined immunogenicity at 3- and 6-months boosting intervals. ResultsThe solicited adverse events (AEs) were mild to moderate and well-tolerated. Total RBD immunoglobulin (Ig), anti-RBD IgG, focus reduction neutralization test (FRNT50) against delta and omicron variants, and T cell response were highest in the mRNA-1273 group followed by the BNT162b2, AZD1222 and BBIBP groups, respectively. We also witnessed a higher total Ig anti-RBD in the long-interval than in the short-interval groups. ConclusionsAll four booster vaccines significantly increased binding and NAbs in individuals immunized with two doses of CoronaVac. The present evidence may benefit vaccine strategies development to thwart variants of concern, including the omicron variant.

COVID-19 breakthrough infection after inactivated vaccine induced robust antibody responses and cross-neutralization of SARS-CoV-2 variants, but less immunity against omicron

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the waning of immunity in vaccinated individuals is resulting in increased numbers of SARS-CoV-2 breakthrough infections. This study investigated binding antibody responses and neutralizing activities against SARS-CoV-2 variants in patients with COVID-19 who had been fully vaccinated with CoronaVac (n = 78), individuals who had been fully vaccinated with CoronaVac but had not contracted COVID-19 (n = 170), and individuals who had received AZD1222 as a third vaccination (n = 210). Breakthrough infection was generally detected approximately 88 days after the second CoronaVac vaccination (interquartile range 68-100) days. Blood samples were collected at median of 34 days after infection. Binding antibody levels in sera from patients with breakthrough infection were significantly higher than those in individuals who had received AZD1222 as a third vaccination. However, neutralizing activities against wild-type and variants including alpha (B.1.1.7), beta (B.1.351), and delta (B.1.617.2) were comparable in patients with breakthrough infections and individuals who received a third vaccination with AZD1222, which activities are exceeding 90%. Omicron (B.1.1.529) was neutralized less effectively by serum from breakthrough infection patients, with a 6.3-fold reduction compared to delta variants. The study suggests that breakthrough infection after two doses of an inactivated vaccine can induce neutralizing antibody against omicron. Further investigation is needed to assess the long-term persistence of antibody against omicron variant.