Real-World Study: Hybrid Immunity against SARS-CoV-2 Influences the Antibody Levels and Persistency Lasting More than One Year.

This study investigated the impact of hybrid immunity on antibody responses in the participants who received two to seven doses of the COVID-19 vaccine. The study was conducted between April and June 2023. Out of 771 serum samples analyzed, 71.7% exhibited hybrid immunity (positive for total anti-N Ig), while 28.3% showed vaccine-induced immunity (negative for total anti-N Ig). Participants were categorized based on the number of vaccine doses: 2, 3, 4, and ≥5. The findings highlight a trend where a higher number of vaccine doses received was associated with a lower infection rate. There was no significant difference in total RBD Ig levels between those who received 3, 4, or ≥5 doses in both the hybrid immunity and vaccination alone groups across all observed durations as follows: <6 months, 6 to <9 months, 9 to <12 months, and ≥12 months. Hybrid immunity consistently maintained higher total RBD Ig levels and durability compared to vaccination alone, with estimated half-lives (T1/2) of 189.5 days versus 106.8 days for vaccine alone. This investigation underscored the potential benefit of hybrid immunity and raised questions about the optimal strategies for further vaccine dosing.

SARS-CoV-2 Antibody Dynamics after COVID-19 Vaccination and Infection: A Real-World Cross-Sectional Analysis.

The Coronavirus disease 2019 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), continues to surge despite the widespread use of vaccination. In Thailand, more than 77% and 39% of the population received two doses and three doses of COVID-19 vaccines as of December 2022, respectively. In addition, during the Omicron predominant period in 2022, more than 70% of Thai individuals have been infected. To gain comprehensive insight into SARS-CoV-2 antibody dynamics following vaccination or following vaccination and infection (hybrid immunity), we performed a cross-sectional analysis of sera samples from individuals who received COVID-19 vaccination and/or have been infected with COVID-19 in Thailand between January 2021 and December 2022. A total of 4126 samples were collected. Humoral immunity was evaluated by quantifying the immunoglobulin (including IgG, IgM, and IgA isotypes) specific to the SARS-CoV-2 receptor-binding domain (RBD) or Ig anti-RBD. The results showed that individuals who received two-dose vaccination alone had lower levels of Ig anti-RBD, which rapidly waned over time. To restore the waning antibody, a third dose vaccination is recommended for uninfected individuals who have only received 2 doses.

Immunogenicity of heterologous inactivated and adenoviral-vectored COVID-19 vaccine: Real-world data.

Limited data are available on the responses to heterologous vaccine regimens for SARS-CoV-2, especially among countries using inactivated and adenoviral-vectored vaccines. A total of 77 participants who received heterologous inactivated COVID-19 vaccine (CoronaVac) and adenoviral-vectored vaccine (AZD1222) were enrolled in our study. There were two comparison groups vaccinated with the homologous CoronaVac (N = 79) and AZD1222 (N = 78) regimen. All sera samples were tested for anti-receptor-binding-domain IgG (anti-RBD IgG) using a chemiluminescent microparticle immunoassay (CMIA). The neutralizing activity in a subset of serum samples was tested against the original Wuhan strain and variants of concern, B.1.1.7, B.1.617.2 and B.1.351, using an enzyme-linked immunosorbent assay (ELISA)-based surrogate virus neutralization test (sVNT). The heterologous CoronaVac/AZD1222 vaccine induced higher levels of anti-RBD IgG than that of two-dose homologous CoronaVac or AZD1222 vaccines (p < 0.001). Sera samples of the CoronaVac/AZD1222 vaccine recipients elicited higher neutralizing antibody activity against the original Wuhan and all variants of concern than in the recipients of the two-dose CoronaVac. The heterologous CoronaVac followed by AZD1222 is an alternative regimen to combat with the SARS-CoV-2 variants in case of vaccine shortage with improved immunogenicity compared to the homologous CoronaVac regimen.

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 = 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.

Immunogenicity of a third dose viral-vectored COVID-19 vaccine after receiving two-dose inactivated vaccines in healthy adults.

In June 2021, Thailand was hit by the delta variant of SARS-CoV-2 resulting in the biggest wave of COVID-19. Due to the widespread delta variant, more than 600 healthcare workers had COVID-19 despite completion of two-dose CoronaVac. The Ministry of Public Health recommended that healthcare workers received a third dose of AZD1222 to increase level of protection against SARS-CoV-2. However, immune response after the AZD1222 booster in individuals who completed the two-dose CoronaVac vaccine are limited. In this study, sera from those who received a booster of AZD1222 in June-July 2021 were tested for SARS-CoV-2 spike receptor-binding-domain (RBD) IgG, anti-RBD total immunoglobulins and anti-spike protein 1 (S1) IgA. The neutralizing activities in a subset of serum samples were tested against the wild type and variants of concern (B.1.1.7, B.1.617.2, and B.1.351) using an enzyme-linked immunosorbent assay-based surrogate virus neutralization test. Participants who received the booster of AZD1222 possessed higher levels of spike RBD-specific IgG, total immunoglobulins, and anti-S1 IgA than the two-dose vaccinees (p < 0.001). They also elicited higher neutralizing activity against the wild type and all variants of concern than the recipients of the two-dose vaccines. This study demonstrated a high immunogenicity of the AZD1222 booster in individuals who completed the two-dose inactivated vaccines.

Prevalence of antibodies against seasonal influenza A and B viruses among older adults in rural Thailand: A cross-sectional study.

Assessing the seroprevalence of the high-risk individuals against the influenza virus is essential to evaluate the progress of vaccine implementation programs and establish influenza virus interventions. Herein, we identified the pre-existing cross-protection of the circulating seasonal influenza viruses among the older-aged population. A cross-sectional study was performed base on the 176 residual sera samples collected from older adults aged 60 to 95 years without a history of vaccination in rural Thailand in 2015. Sera antibody titers against influenza A and B viruses circulating between 2016 and 2019 were determined by hemagglutination inhibition assay. These findings indicated the low titers of pre-existing antibodies to circulating influenza subtypes and showed age-independent antibody titers among the old adults. Moderate seropositive rates (HAI ≥ 1:40) were observed in influenza A viruses (65.9%A(H3N2), 50.0% for A(H1N1) pdm09), and found comparatively lower rates in influenza B viruses (14% B/Yam2, 21% B/Yam3 and 25% B/Vic). Only 5% of individuals possessed broadly protective antibodies against both seasonal influenza A and B virus in this region. Our findings highlighted the low pre-existing antibodies to circulating influenza strains in the following season observed in older adults. The serological study will help inform policy-makers for health care planning and guide control measures concerning vaccination programs.