Search

Numerous studies have largely focused on short-term immunogenicity in recovered individuals post mRNA vaccination. However, understanding the long-term durability, particularly in inactivated and adenoviral vectored vaccines, remains limited. We evaluated antibody responses, omicron variant neutralization, and IFN-γ responses in 119 previously infected individuals vaccinated with CoronaVac or ChAdOx1 up to six months post-vaccination. Both vaccines elicited robust immune responses in recovered individuals, surpassing those who were infection-naïve, and these persisted above pre-vaccination levels for six months. However, antibody levels declined over time (geometric mean ratio (GMR) = 0.52 for both vaccines). Notably, neutralizing activities against omicron declined faster in ChAdOx1 (GMR = 0.6) compared to CoronaVac recipients (GMR = 1.03). While the first dose of ChAdOx1 adequately induced immune responses in recovered individuals, a second dose demonstrated advantages in omicron variant neutralization and slower decline. Although both vaccines induced T cell responses, the median IFN-γ level at six months returned to pre-vaccination levels. However, more individuals exhibited reactive T cell responses. Extending the interval (13–15 months) between infection and vaccination could enhance antibody levels and broaden neutralization. Together, these findings demonstrate a robust humoral and cellular response that was sustained for at least six months after vaccination, thus guiding optimal vaccination strategies based on prior infection and vaccine platforms. [ABSTRACT FROM AUTHOR]

To compare the reactogenicity and immunogenicity between the two‐dose mRNA COVID‐19 vaccine regimen and one or two doses of inactivated vaccine followed by an mRNA vaccine regimen in healthy children between 5 and 11 years of age, a prospective cohort study was performed at King Chulalongkorn Memorial Hospital in Thailand between March to June 2022. Healthy children between 5 and 11 years of age were enrolled and received the two‐dose mRNA COVID‐19 vaccine (BNT162b2) regimen or the inactivated (CoronaVac) vaccine followed by the BNT162b2 vaccine regimen. In addition, healthy children who received two doses of BBIBP‐CorV between 1 and 3 months prior were enrolled to receive a heterologous BNT162b2 as a third dose (booster). Reactogenicity was assessed by a self‐reported online questionnaire. Immunogenicity analysis was performed to determine binding antibodies to wild‐type SARS‐CoV‐2. Neutralizing antibodies to Omicron variants (BA.2 and BA.5) were tested using the focus reduction neutralization test. Overall, 166 eligible children were enrolled. Local and systemic adverse events which occurred within 7 days after vaccination were mild to moderate and well‐tolerated. The two‐dose BNT162b2, CoronaVac followed by BNT162b2, and two‐dose BBIBP‐CorV followed by BNT162b2 groups elicited similar levels of anti‐receptor‐binding domain (RBD) IgG. However, the two‐dose BNT162b2 and two‐dose BBIBP‐CorV followed by BNT162b2 groups elicited higher neutralizing activities against the Omicron BA.2 and BA.5 variant than the CoronaVac followed by BNT162b2 group. The CoronaVac followed by BNT162b2 group elicited low neutralizing activities against the Omicron BA.2 and BA.5 variant. A third dose (booster) mRNA vaccine should be prioritized for this group. [ABSTRACT FROM AUTHOR]

The coronavirus 2019 omicron variant has surged rapidly and raises concerns about immune evasion even in individuals with complete vaccination, because it harbors mutations. Here we examine the capability of booster vaccination following CoronaVac/AZD1222 prime to induce neutralizing antibodies (NAbs) against omicron (BA.1 and BA.2) and T‐cell responses. A total of 167 participants primed with heterologous CoronaVac/AZD1222 for 4–5 months were enrolled, to receive AZD1222, BNT162b2, or mRNA‐1273 as a third dose. Reactogenicity was recorded. Immunogenicity analyses of severe acute respiratory syndrome coronavirus 2‐binding antibodies were measured using enzyme‐linked immunosorbent assay. The NAb titers against omicron BA.1 and BA.2 were determined using the focus reduction neutralization test (FRNT50) and total interferon‐γ responses were measured to observe the T‐cell activation. A substantial loss in neutralizing potency to omicron variant was found at 4–5 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. In addition, individuals boosted with messenger RNA (mRNA) vaccines develop a T‐cell response to spike protein, whereas those boosted with AZD1222 did not. Reactogenicity was mild to moderate without serious adverse events. Our findings demonstrated that mRNA booster vaccination is able to overcome waning immunity to provide antibodies that neutralize omicron BA.1 and BA.2, as well as a T‐cell response. [ABSTRACT FROM AUTHOR]

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 anti-RBD IgG 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) 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 at the cut-off value ≥148 BAU/mL and ≥138 BAU/mL were related to the threshold for FRNT50 titers ≥20 against BA.1 and BA.2, respectively. A moderate correlation was observed between the sVNT and FRNT50 titers. At FRNT50 titers ≥20, the predicted sVNT for BA.1 and BA.2 was ≥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. [ABSTRACT FROM AUTHOR]

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 = 77), 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 a 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 exceeds 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 antibodies against omicron. Further investigation is needed to assess the long-term persistence of antibodies against the omicron variant. [ABSTRACT FROM AUTHOR]

• One-dose vaccination or pre-Omicron-infected sera failed to neutralize Omicron BA.5. • Omicron convalescent sera had detectable cross-reactive neutralizing antibody (nAb), but the titer was low. • Two-dose vaccination exhibited similar nAb titers compared with Omicron-infected sera. • Hybrid immunity showed the highest nAb, followed by vaccination and convalescent sera. To assess the binding antibody response and strength of neutralization against Omicron BA.5 in serum samples from children with different antigen exposures (infection/vaccination) and hybrid immunity. This study recruited children aged 5-7 years. All samples were tested for anti-nucleocapsid immunoglobulin (Ig)G, anti-receptor binding domain (RBD) IgG, and total anti-RBD Ig. Neutralizing antibodies (nAbs) against Omicron BA.5 were determined using a focus reduction neutralization test. A total of 196 serum samples from unvaccinated children with infection (n = 57), vaccination alone (n = 71), and hybrid immunity (n = 68). Our results showed that 90% of the samples from children with hybrid immunity, 62.2% from two-dose vaccination, and 48% from Omicron infection alone had detectable nAbs against Omicron BA.5. The highest neutralizing titer was observed in infection plus two-dose vaccination, which reached 6.3-fold increase, whereas nAb titers in two-dose vaccination was comparable to Omicron-infected sera. However, sera from pre-Omicron infection and single-dose vaccination failed to neutralize Omicron BA.5; although, the total anti-RBD Ig were comparable with Omicron-infected sera. This result highlights that hybrid immunity provided cross-reactive antibodies to neutralize Omicron BA.5 compared with either vaccination or infection alone. The finding emphasizes the importance of vaccination in unvaccinated children who are infected with pre-Omicron or Omicron variants. [ABSTRACT FROM AUTHOR]

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 μg- than the 30 μg-BNT162b2 groups, whereas joint pain and chilling were more frequent in the 100 μg- than the 50 μg-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. [ABSTRACT FROM AUTHOR]

• The messenger RNA (mRNA) booster produced a high cross-neutralization level against the Omicron variant. • The half-dose mRNA-1273 elicited total immunoglobulin (Ig) and anti-receptor-binding domain IgG equal to the full dose. • The neutralizing activity thwarting the BA.1 and BA.2 variants was comparable in the mRNA booster. • Clusters of differentiation (CD), CD4+ and CD8+ T cell responses were restored after the mRNA booster vaccination. • The additional fourth dose should be implemented for AZD1222-boosted individuals. The 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. Participants who completed the Oxford/AstraZeneca (hereafter AZD1222) vaccine dose 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 messenger RNA (mRNA) vaccines (BNT162b2, full, or half-dose mRNA-1273) administered 6 months after primary vaccination were determined. A total of 229 individuals enrolled, and waning of immunity was observed 5-7 months after the AZD1222-primed vaccinations. Total receptor-binding domain (RBD) immunoglobulin (Ig) levels, anti-RBD IgG, and focus reduction neutralization test against Omicron BA.1 and BA.2 variants and T cell response peaked at 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 for all vaccines. A heterologous mRNA booster provided a significantly superior boost of binding and NAbs levels against the Omicron variant compared with a homologous booster in individuals with AZD1222-primed vaccinations. [ABSTRACT FROM AUTHOR]