Characteristics of SARS-CoV-2 reinfection with Omicron BA.2.75 subvariants in Thai Adults. (preprint)

Omicron subvariants of SARS-CoV-2 may resist vaccine- or infection-induced immunity thereby increasing the risk of reinfections in previously infected persons. This study aimed to investigate the clinical severity and the average time to the onset of Omicron reinfection. This survey study collected clinical data on Omicron reinfection. Information on time of infection, reinfection interval, overall clinical presentation, and severity of infection was reported. The total prevalence of symptoms among 201 participants was significantly higher in the first infection (risk difference (RD), 9.86%; 95% CI, 7.54-12.19]) compared to the second infection, and the hospitalization rate among all participants was significantly lower for the second infection than the primary infection (odds ratio (OR), 6.25; 95% CI, 2.158-24.71). The prevalence of symptoms compared with the first infection with pre-Omicron variants was similar to that of the first infection with the Omicron variant (RD, 2.56%; 95% CI, -6.14-1.01). However, the hospitalization rate for pre-Omicron primary infection was significantly higher (OR, 6.76; 95% CI, 2.87-15.87]) than that observed with Omicron variants. The severity of the primary infection and of a pre-Omicron variant was greater than that of a secondary infection or with an Omicron variant.

The fourth dose of mRNA COVID-19 vaccine following 12 different three-dose regimens: Safety and immunogenicity to Omicron BA.4/BA.5 (preprint)

Objective: To investigate the reactogenicity and immunogenicity of the fourth dose using mRNA vaccines after different three-dose regimens and to compare the 30 g BNT162b2 and 50 g mRNA-1273 vaccines. Methods: This prospective cohort study was conducted between June and October 2022. The self-recorded reactogenicity was evaluated on the subsequent 7 days after a fourth dose. Binding and neutralizing activity of antibodies against the Omicron BA.4/5 variants were determined. Results: Overall, 292 healthy adults were enrolled and received BNT162b2 or mRNA-1273. Reactogenicity was mild to moderate and well-tolerated after a few days. Sixty-five individuals were excluded. Thus, 227 eligible individuals received a fourth booster dose of BNT162b2 (n=109) and mRNA-1273 (n=118). Most participants, regardless the type of previous three dose regimens, elicited a significantly high level of binding antibodies and neutralizing activity against the Omicron BA.4/5 28 days after a fourth dose. The neutralizing activity against the Omicron BA.4/5 between the BNT162b2 (82.8%) and mRNA-1273 (84.2%) groups was comparable with a median ratio of 1.02. Conclusion: This study found that the BNT162b2 and mRNA-1273 vaccines can be used as a fourth booster dose for individuals who were previously immunized with any prior mix and match three dose COVID-19 vaccine.

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 (preprint)

Objectives: Several 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. Methods: A 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. Results: A 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. Conclusions: The 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.

Safety and immunogenicity of a third dose of COVID-19 protein subunit vaccine (CovovaxTM) after homologous and heterologous two-dose regimens (preprint)

Objective: To report the safety and immunogenicity profile of a protein subunit vaccine (CovovaxTM) given as a third (booster) dose to individuals primed with different primary vaccine regimens. Methods: Individuals primed with two doses of COVID-19 vaccines for at least 3 months were enrolled and assigned to five groups according to their primary vaccine regimens: CoronaVac, BBIBP-CorV, AZD1222, BNT162b2, and CoronaVac/AZD1222. Immunogenicity analysis was performed to determine binding antibodies, neutralizing activity, and the T-cell response. Results: Overall, 215 individuals were enrolled and boosted with the CovovaxTM vaccine. The reactogenicity achieved was mild-to-moderate. Most participants elicited a high level of binding and neutralizing antibody responses against wild type and omicron variants following the booster dose. The 197 participants were classified by anti-N IgG. Of these, 141/197 (71.6%) were a seronegative population, and neutralizing activity and IFN-{gamma} release were further monitored. A booster dose could elicit neutralizing activity to wild type and omicron variants by more than 95% and 70% inhibition at 28 days, respectively. The CovovaxTM vaccine could elicit a cell-mediated immune response. Conclusion: The protein subunit vaccine (CovovaxTM) can be proposed as a booster dose after two different priming dose regimens. It has strong immunogenicity and good safety profiles. Keywords: Severe acute respiratory virus 2 (SARS-CoV-2); Omicron; side effect; CovovaxTM; Novavax; booster dose

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 (preprint)

Objectives: 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. Methods: Participants 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. Results: Total 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. Conclusions: A 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.

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. (preprint)

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.

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

Background The 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. Methods A 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. Results The 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. Conclusions All 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.

Safety and immunogenicity of the third booster dose with inactivated, viral vector, and mRNA COVID-19 vaccines in fully immunized healthy adults with inactivated vaccine (preprint)

The coronavirus disease-2019 (COVID-19) pandemic has become a severe healthcare problem worldwide since the first outbreak in late December 2019. Currently, the COVID-19 vaccine has been used in many countries, but it is still unable to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection despite patients receiving full vaccination doses. Therefore, we aimed to appraise the booster effect of the different platforms of vaccines, including inactivated vaccine (BBIBP), viral vector vaccine (AZD122), and mRNA vaccine (BNT162b2) in healthy adults who received the full dose of inactivated vaccine (CoronaVac). The booster dose was safe with no serious adverse events. Moreover, the immunogenicity indicated that the booster dose with viral vector and mRNA vaccine achieved a significant proportion of Ig anti-receptor binding domain (RBD), IgG anti-RBD, and IgA anti-S1 booster response. In contrast, inactivated vaccine achieved a lower booster response than others. Consequently, the neutralization activity of vaccinated serum had a high inhibition of over 90% against SARS-CoV-2 wild-type and their variants (B.1.1.7–alpha, B.1.351–beta, and B.1.617.2–delta). In addition, IgG anti-nucleocapsid was observed only among the group that received the BBIBP booster. Our study found a significant increase in levels of interferon gamma-secreting T-cell response after the additional viral vector or mRNA booster vaccination. This study showed that administration with either viral vector (AZD1222) or mRNA (BNT162b2) boosters in individuals with a history of two doses of inactivated vaccine (CoronaVac) obtained great immunogenicity with acceptable adverse events.