SARS-CoV-2 Seroprevalence in Unvaccinated Adults in Thailand in November 2021.

Between the first case of COVID-19 in January 2020 and the end of 2021, Thailand experienced four waves of the epidemic. The third and fourth waves were caused by the alpha and delta strains from April 2021 to November 2021. Serosurveillance studies provide snapshots of the true scale of the outbreak, including the asymptomatic infections that could not be fully captured by a hospital-based case detection system. We aimed to investigate the distribution of SARs-CoV-2 seroprevalence in unvaccinated adults after the delta wave outbreak. From November to December 2021, we conducted a cross-sectional survey study in 12 public health areas (PHAs) across Thailand. A total of 26,717 blood samples were collected and tested for SARs-CoV-2 antibodies (anti-S IgG) using a qualitative immunoassay. The results showed that seropositive prevalence in this cohort was 1.4% (95% CI: 1.24 to 1.52). The lowest prevalence was in the northern region (PHA 1) and in central Thailand (PHA 3) at 0.4% (95% CI: 0.15 to 0.95), while the highest was in the southern region of Thailand (PHA 12) at 5.8% (95% CI: 4.48 to 7.29). This seropositive prevalence was strikingly lower than the reports from other countries. Our serosurveillance results suggest that the vaccination of unvaccinated groups should be accelerated, especially in the public health areas with the lowest seroprevalence.

The Pilot Study of Immunogenicity and Adverse Events of a COVID-19 Vaccine Regimen: Priming with Inactivated Whole SARS-CoV-2 Vaccine (CoronaVac) and Boosting with the Adenoviral Vector (ChAdOx1 nCoV-19) Vaccine.

In response to the SARS-CoV-2 Delta variant, which partially escaped the vaccine-induced immunity provided by two doses of vaccination with CoronaVac (Sinovac), the National Vaccine Committee recommended the heterologous CoronaVac-ChAdOx1 (Oxford−AstraZeneca), a prime−boost vaccine regimen. This pilot study aimed to describe the immunogenicity and adverse events of the heterologous CoronaVac-ChAdOx1 regimen, in comparison with homologous CoronaVac, and homologous ChAdOx1. Between May and August 2021, we recruited a total of 354 participants from four vaccination groups: the CoronaVac-ChAdOx1 vaccinee (n = 155), the homologous CoronaVac vaccinee (n = 32), the homologous ChAdOx1 vaccinee (n = 47), and control group of COVID-19 patients (n = 120). Immunogenicity was evaluated by measuring the level of IgG antibodies against the receptor-binding domain (anti-SRBD) of the SARS-CoV-2 spike protein S1 subunit and the level of neutralizing antibodies (NAbs) against variants of concern (VOCs) using the plaque reduction neutralization test (PRNT) and pseudovirus neutralization test (pVNT). The safety profile was recorded by interviewing at the 1-month visit after vaccination. The anti-SRBD level after the second booster dose of the CoronaVac-ChAdOx1 group at 2 weeks was higher than 4 weeks. At 4 weeks after the second booster dose, the anti-SRBD level in the CoronaVac-ChAdOx1 group was significantly higher than either homologous CoronaVac, the homologous ChAdOx1 group, and Control group (p < 0.001). In the CoronaVac-ChAdOx1 group, the PRNT50 level against the wild-type (434.5 BAU/mL) was the highest; followed by Alpha variant (80.4), Delta variant (67.4), and Beta variant (19.8). The PVNT50 level was also found to be at its highest against the wild-type (432.1); followed by Delta variants (178.3), Alpha variants (163.9), and Beta variant (42.2), respectively. The AEs in the CoronaVac-ChAdOx1 group were well tolerated and generally unremarkable. The CoronaVac-ChAdOx1 heterologous regimen induced higher immunogenicity and a tolerable safety profile. In a situation when only CoronaVac-ChAdOx1 vaccines are available, they should be considered for use in responding to the Delta variant.

Prime-boost immunization of codon optimized HIV-1 CRF01_AE Gag in BCG with recombinant vaccinia virus elicits MHC class I and II immune responses in mice.

The HIV-1 CRF01_AE gag gene was modified by codon restriction for Mycobacterium spp. and transformed into BCG; and it was designated as rBCG/codon optimized gagE. This produced 11 fold higher HIV-1 gag protein expression than the recombinant native gene rBCG/HIV-1gagE. In mice, CTL activity could be induced either by a single immunization of the codon optimized construct or by using it as a priming antigen in the prime-boost modality with recombinant Vaccinia virus expressing native HIV-1 gag. Specific secreted cytokine responses were also investigated. Only when rBCG gag was codon optimized did the prime-boost immunization produce significantly enhanced IFN-gamma and IL-2 secretion indicating recognition via CD4+ and CD8+ T cells, and these responses seemed to be codon optimized immunogen dose-responsive. On contrary, the prime-boost vaccination using an equal amount of native rBCG/HIV-1gagE instead, or a single rBCG/codon optimized gagE immunization, had no similar effect on the cytokine secretion. These findings suggest that the use of recombinant codon BCG construct with recombinant Vaccinia virus encoding CRF01_AE gag as the prime-boost HIV vaccine candidate, will induce CD4+ Th1 and CD8+ T cell cytokine secretions in addition to enhancing CD8+ CTL response.

Enhancement of cell-mediated immune response in mice by whole HIV-1 gag in Mycobacterium bovis BCG as a live vaccine candidate.

In this study, we employed a recombinant Mycobacterium bovis Bacille Calmette-Guerin (BCG) harboring whole HIV-1 CRF01_AE gag DNA as a candidate vaccine to investigate specific cell-mediated immunity in BALB/c mice. Construction of the stable expression recombinant BCG was achieved by demonstrating by Western blot detection of protein of approximately 55 kDa. By a single injection of 0.1 mg of the recombinant HIV-1 gag protein expressing BCG subcutaneously into mice, after 2 weeks various specific cytotoxic T-lymphocyte (CTL) responses were exhibited against a single gag epitope of amino acid positions 294-304, and also against various peptide regions along the entire gag protein with moderate CTL activities (10-35% specific cell lysis), which increased to relatively high levels (50-68%) after one month. However, after two months activities were 3-3.7 fold lower. On the other hand, gag-specific lymphocyte proliferation was detected 9.3 fold higher than that of non-immunized mouse spleen cells. Our results indicate that in mice, BCG can be used as a recombinant live vector to induce cellular immune responses to HIV-1 gag antigen.

Prime-boost vaccination using recombinant Mycobacterium bovis BCG and recombinant vaccinia virus DIs harboring HIV-1 CRF01_AE gag in mice: influence of immunization routes.

We have previously reported that live vector-based HIV-1 gag vaccine candidate using BCG as a vector was achievable in BALB/c mice. Although the gag-specific CTL induced by this live candidate vaccine is significantly high, persistence of CTL remains unclear. Thus, efforts were made to explore the potential of recombinant Vaccinia virus DIs strain harboring the same HIV-1 CRF01_AE gag gene (rVaccinia/ HIV-1gagE) present in the BCG construct, using different immunization routes. After one month following a single subcutaneous (s.c.) injection of rBCG/HIV-1gagE, higher CTL responses were recognized against various peptide epitopes along the whole gag protein compared to that by intradermal (i.d.) route. A prime-boost regimen having only rDIs/HIV-1gagE injected i.d. induced very low CTL levels. However, within two months, by priming with rBCG/HIV-1gagE s.c. and boosting with rVaccinia/HIV-1gagE intravenously (i.v.), CTL levels were greater (20-68% specific cell lysis) than those obtained by priming and boosting both i.d. (18-35%). After seven months, both prime-boost immunization with rBCG/HIV-lgagE s.c. and with rVaccinia/HIV-1gagE either i.v. or i.d. sustained similar CTL levels. Our studies exhibit that the prime-boost vaccination of rBCG/HIV-1gagE following by rVaccinia/HIV-1gagE i.d. could be used to elicit prolonged CTL responses as well as memory T-cells in mice, which might be more practical than using i.v. route.