Whole-inactivated SARS-CoV-2 vaccines: from fear to hope

Undoubtedly, vaccination can be one of the promising approaches to control infectious diseases such as the COVID-19 pandemic. Inactivated viral vaccines have a history of "vaccine-induced enhanced disease", which may occur when neutralizing antibodies bind to viral antigens without blocking or clearing the infection. This can cause additional inflammation through the mechanisms described for other respiratory pathogens and lead to acute respiratory distress syndrome. Since the structure and function of SARS-CoV-2 glycoproteins are well known, vaccine manufacturers appear to be careful when inactivating the virus to completely inactivate and maintain the viral epitopes necessary for protective immune induction. It seems that caution should be taken in the usage of inactivated vaccines in children to ensure they are safe and efficacious, vaccinated children should be well monitored and any symptoms should be reported immediately.

Efficacy and effectiveness of inactivated vaccines against symptomatic COVID-19, severe COVID-19, and COVID-19 clinical outcomes in the general population: a systematic review and meta-analysis.

Background: Inactivated, whole-virion vaccines have been used extensively in the SARS-CoV-2 pandemic. Its efficacy and effectiveness across regions have not been systematically evaluated. Efficacy refers to how well a vaccine performs in a controlled environment. Effectiveness refers to how well it performs in real world settings. Methods: This systematic review and meta-analysis reviewed published, peer-reviewed evidence on all WHO-approved inactivated vaccines and evaluated their efficacy and effectiveness against SARS-CoV-2 infection, symptomatic infection, severe clinical outcomes, and severe COVID-19. We searched Pubmed (including MEDLINE), EMBASE (via OVID), Web of Science Core Collection, Web of Science Chinese Science Citation Database, and Clinicaltrials.gov. Findings: The final pool included 28 studies representing over 32 million individuals reporting efficacy or effectiveness estimates of complete vaccination using any approved inactivated vaccine between January 1, 2019 and June 27, 2022. Evidence was found for efficacy and effectiveness against symptomatic infection (OR 0.21, 95% CI 0.16-0.27, I2 = 28% and OR 0.32, 95% CI 0.16-0.64, I2 = 98%, respectively) and infection (OR 0.53, 95% CI 0.49-0.57, I2 = 90% and OR 0.31, 95% CI 0.24-0.41, I2 = 0%, respectively) for early SARS-CoV-2 variants of concern (VoCs) (Alpha, Delta), and for waning of vaccine effectiveness with more recent VoCs (Gamma, Omicron). Effectiveness remained robust against COVID-related ICU admission (OR 0.21, 95% CI 0.04-1.08, I2 = 99%) and death (OR 0.08, 95% CI 0.00-2.02, I2 = 96%), although effectiveness estimates against hospitalization (OR 0.44, 95% CI 0.37-0.53, I2 = 0%) were inconsistent. Interpretation: This study showed evidence of efficacy and effectiveness of inactivated vaccines for all outcomes, although inconsistent reporting of key study parameters, high heterogeneity of observational studies, and the small number of studies of particular designs for most outcomes undermined the reliability of the findings. Findings highlight the need for additional research to address these limitations so that more definitive conclusions can be drawn to inform SARS-CoV-2 vaccine development and vaccination policies. Funding: Health and Medical Research Fund on COVID-19, Health Bureau of the Government of the Hong Kong SAR.

Dynamic immunogenicity after primary and booster inactivated SARS-CoV-2 vaccination in people living with HIV: A longitudinal observational study.

People living with HIV (PLWH) have poor outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); vaccination reduces the associated mortality. The humoral immune response dynamics after booster inactivated vaccinations in PLWH remain unclear. In this longitudinal observational study, 100 PLWH after primary inactivated SARS-CoV-2 vaccination were consecutively recruited and followed up. After booster vaccination (BV), neutralizing antibodies (NAbs) were detected at 1 month from all the PLWH, and the titer increased sixfold compared to that associated with the primary vaccination (PV), similar to that in healthy controls after BV. The NAbs titer declined over time after BV, but remained higher at 6 months than after PV. The NAbs response was elevated after BV with CD4 count <200 cells/µL, it was the poorest among the different CD4 cell count subgroups. Similar results were observed for anti-RBD-IgG responses. Moreover, RBD-specific MBCs were significantly elevated after BV in PLWH. No serious AEs were observed after BV in PLWH. In conclusion, booster inactivated SARS-CoV-2 vaccination is well tolerated and can elicit robust and durable humoral responses in PLWH. PLWH may benefit from a third dose of the inactivated vaccine.

Non-spike and spike-specific memory T cell responses after the third dose of inactivated COVID-19 vaccine.

Background: During the COVID-19 epidemic, vaccination has become the most safe and effective way to prevent severe illness and death. Inactivated vaccines are the most widely used type of COVID-19 vaccines in the world. In contrast to spike-based mRNA/protein COVID-19 vaccines, inactivated vaccines generate antibodies and T cell responses against both spike and non-spike antigens. However, the knowledge of inactivated vaccines in inducing non-spike-specific T cell response is very limited. Methods: In this study, eighteen healthcare volunteers received a homogenous booster (third) dose of the CoronaVac vaccine at least 6 months after the second dose. CD4+ and CD8+ T cell responses against a peptide pool from wild-type (WT) non-spike proteins and spike peptide pools from WT, Delta, and Omicron SARS-CoV-2 were examined before and 1-2 weeks after the booster dose. Results: The booster dose elevated cytokine response in CD4+ and CD8+ T cells as well as expression of cytotoxic marker CD107a in CD8+ T cells in response to non-spike and spike antigens. The frequencies of cytokine-secreting non-spike-specific CD4+ and CD8+ T cells correlated well with those of spike-specific from WT, Delta, and Omicron. Activation-induced markers (AIM) assay also revealed that booster vaccination elicited non-spike-specific CD4+ and CD8+ T cell responses. In addition, booster vaccination produced similar spike-specific AIM+CD4+ and AIM+CD8+ T cell responses to WT, Delta, and Omicron, indicting strong cross-reactivity of functional cellular response between WT and variants. Furthermore, booster vaccination induced effector memory phenotypes of spike-specific and non-spike-specific CD4+ and CD8+ T cells. Conclusions: These data suggest that the booster dose of inactive vaccines broadens both non-spike-specific and spike-specific T cell responses against SARS-CoV-2.

No association of vaccination with inactivated COVID-19 vaccines before conception with pregnancy complications and adverse birth outcomes: A cohort study of 5457 Chinese pregnant women.

Data on the safety of inactivated COVID-19 vaccines in pregnant women is limited and monitoring pregnancy outcomes is required. We aimed to examine whether vaccination with inactivated COVID-19 vaccines before conception was associated with pregnancy complications or adverse birth outcomes. We conducted a birth cohort study in Shanghai, China. A total of 7000 healthy pregnant women were enrolled, of whom 5848 were followed up through delivery. Vaccine administration information was obtained from electronic vaccination records. Relative risks (RRs) of gestational diabetes mellitus (GDM), hypertensive disorders in pregnancy (HDP), intrahepatic cholestasis of pregnancy (ICP), preterm birth (PTB), low birth weight (LBW), and macrosomia associated with COVID-19 vaccination were estimated by multivariable-adjusted log-binomial analysis. After exclusion, 5457 participants were included in the final analysis, of whom 2668 (48.9%) received at least two doses of an inactivated vaccine before conception. Compared with unvaccinated women, there was no significant increase in the risks of GDM (RR = 0.80, 95% confidence interval [CI], 0.69, 0.93), HDP (RR = 0.88, 95% CI, 0.70, 1.11), or ICP (RR = 1.61, 95% CI, 0.95, 2.72) in vaccinated women. Similarly, vaccination was not significantly associated with any increased risks of PTB (RR = 0.84, 95% CI, 0.67, 1.04), LBW (RR = 0.85, 95% CI, 0.66, 1.11), or macrosomia (RR = 1.10, 95% CI, 0.86, 1.42). The observed associations remained in all sensitivity analyses. Our findings suggested that vaccination with inactivated COVID-19 vaccines was not significantly associated with an increased risk of pregnancy complications or adverse birth outcomes.

Specific antibodies of 95 health care workers vaccinated with inactivated 2019-nCoV vaccines

OBJECTIVE: To investigate the immune antibodies in blood specimens of 95 health care workers vaccinated with inactivated 2019-nCoV vaccines and explore the rules and characteristics of production of antibodies after vaccination. METHODS: From Oct 2020 to Jul 2021, the venous blood specimens were collected from 95 health care workers of the 305 Hospital of PLA after the injection of 2 doses of 2019-nCoV vaccines fo30 days, 65 days, 91 days, 6 months and 9 months. SARS-CoV-2 immunoglobin(Ig) M, IgG and titers of neutralizing antibodies and total antibodies were detected by chemiluminescence immunoassay, the results of antibody tests were dynamically analyzed, the immune durability of the antibody, influencing factors and correlation were determined. RESULTS: Almost all of the subjects produced IgG, neutralizing antibody and total antibody, some subjects retained high level of IgM titer. Smoking could affect the production of total antibody. The subjects of the low body weight group produced higher level of IgG, and there was no significant difference when the weight was over 60 kg. The titers of the four types of antibodies decreased significantly at the following time points, and the positive rates of all the antibodies were less than 50% except for IgG after the vaccination for 9 months. CONCLUSION: Specific IgM and IgG, neutralizing antibody and total antibody can be produced after the 2-doses vaccination of inactivated 2019-nCoV vaccines. But the titers and positive rates of the antibodies decrease with time, which means the protective effects on the body decrease. Therefore, in order to improve the autoimmunity against novel coronavirus, one booster vaccination of an inactivated 2019-nCoV vaccine will be necessary after the 2 doses of vaccination for 6 months.

Investigation of long-term follow-up results of COVID-19 disease in kidney transplant patients and the effect of inactive COVID-19 vaccine

Objective: We aimed to evaluate the long-term graft functions of kidney transplant recepients (KTR) who have been cured of the COVID-19 and to investigate the role of inactivated COVID-19 vaccine in the clinical course of the disease. Materials and Methods: KTR who had COVID-19 pneumonia between March 2020 and September 2021 were included in the study.. The clinical course of the disease was evaluated in vaccinated patients and compared with those who were not vaccinated. The laboratory information of the patients at the time of admission to the hospital, 6 months and 12 months after the disease was recorded. Results: Of the 83 patients included, 67.5% were male. COVID-19 disease developed in 20 patients after vaccination. Vaccine;it decreased the development of acute kidney injury (AKI) 5.9 fold and hospitalization in the intensive care unit (ICU) 1.4 times fold (p < 0.05). In the follow-up, 10 patients died at the first admission to the hospital and no late death was recorded in the first year. Dialysis treatment was started in 5 patients due to graft loss. Conclusion: In kidney transplant patients, graft dysfunction may develop after COVID-19 infection. However, the inactivated COVID-19 vaccine;it can reduce the risks of hospitalization, AKI, and ICU admission.

Impact of inactivated vaccines on decrease of viral RNA levels in individuals with the SARS-CoV-2 Omicron (BA.2) variant: A retrospective cohort study in Shanghai, China.

Background: SARS-CoV-2 Omicron (BA.2) has stronger infectivity and more vaccine breakthrough capability than previous variants. Few studies have examined the impact of inactivated vaccines on the decrease of viral RNA levels in individuals with the Omicron variant, based on individuals' continuous daily cycle threshold (Ct) values and associated medical information from the infection to hospital discharge on a large population. Methods: We extracted 39,811 individuals from 174,371 Omicron-infected individuals according to data inclusion and exclusion criteria. We performed the survival data analysis and Generalized Estimating Equation to calculate the adjusted relative risk (aRR) to assess the effect of inactivated vaccines on the decrease of viral RNA levels. Results: Negative conversion was achieved in 54.7 and 94.3% of all infected individuals after one and 2 weeks, respectively. aRRs were shown weak effects on turning negative associated with vaccinations in asymptomatic infections and a little effect in mild diseases. Vaccinations had a protective effect on persistent positivity over 2 and 3 weeks. aRRs, attributed to full and booster vaccinations, were both around 0.7 and had no statistical significance in asymptomatic infections, but were both around 0.6 with statistical significance in mild diseases, respectively. Trends of viral RNA levels among vaccination groups were not significant in asymptomatic infections, but were significant between unvaccinated group and three vaccination groups in mild diseases. Conclusion: Inactivated vaccines accelerate the decrease of viral RNA levels in asymptomatic and mild Omicron-infected individuals. Vaccinated individuals have lower viral RNA levels, faster negative conversion, and fewer persisting positive proportions than unvaccinated individuals. The effects are more evident and significant in mild diseases than in asymptomatic infections.

Do different platforms of coronavirus vaccines have different impacts on psoriasis flares?

This study evaluated the impacts on psoriasis flares of 3 vaccine platforms: inactivated, viral vector and mRNA. Respectively, 198 and 96 psoriasis patients with and without COVID-19 vaccination during the study period. Group comparison revealed no increased risk of psoriasis flaring after COVID-19 vaccination. The vaccinated group received 425 doses of vaccine (140 inactivated, 230 viral vector and 55 mRNA). Patients' self-reported symptoms included all three platforms causing psoriasis flare, but the highest was among patients administered with mRNA vaccines. Most flares were mild to moderate, and most patients (89.8%) managed their flare-up lesions without rescue therapy. In conclusion, our study showed that the rate of psoriasis flare was not significantly different between vaccinated and unvaccinated groups. Factors that might explain psoriasis flare include vaccine-related psychological stress and side effects from vaccination. Different platforms of corona vaccines seemed to have different impact of psoriasis flares. Based on our results and the recommendations of several consensus guidelines, the benefits of COVID vaccinations outweigh the risks to patients with psoriasis. Patients with psoriasis should receive a COVID vaccine as soon as one is available.

Humoral responses after primary and booster SARS-CoV-2 inactivated vaccination in patients with chronic hepatitis B virus infection: A longitudinal observational study.

Given the pandemic of severe acute respiratory syndrome coronavirus 2 Omicron variants, booster vaccination (BV) using inactivated virus vaccines (the third dose) has been implemented in China. However, the immune responses after BV, especially those against Omicron, in patients with chronic hepatitis B virus (HBV) infection (CHB) are unclear. In this prospective longitudinal study, 114 patients with CHB and 68 healthy controls (HCs) were recruited after receiving inactivated vaccination. The anti-receptor-binding domain (RBD) immunoglobulin G (IgG), neutralizing antibodies (NAbs), neutralization against Omicron (BA2.12.1, BA.4/5), and specific B/T cells were evaluated. In patients, anti-RBD IgG was elevated significantly after BV; the titers were as high as those in HCs. Similar results were obtained for the NAbs. However, compared with that against wild type (WT), the neutralization against Omicron was compromised after BV. The frequency of RBD+ atypical memory B cells increased, but spike-specific cluster of differentiation 4+ /8+ T cells remained unchanged after BV. Moreover, no serious adverse events or HBV reactivation were observed after BV. These results suggest that BV significantly enhanced antibody responses against WT; however, it resulted in compromised antibody responses against Omicron in patients with CHB. Hence, new all-in-one vaccines and optimal vaccination strategies should be studied promptly.

Omicron variants escape the persistent SARS-CoV-2-specific antibody response in 2-year COVID-19 convalescents regardless of vaccination.

With the ongoing COVID-19 pandemic and the emergence of various SARS-CoV-2 variants, a comprehensive evaluation of long-term efficacy of antibody response in convalescent individuals is urgently needed. Several longitudinal studies had reported the antibody dynamics after SARS-CoV-2 acute infection, but the follow-up was mostly limited to 1 year or 18 months at the maximum. In this study, we investigated the durability, potency, and susceptibility to immune evasion of SARS-CoV-2-specific antibody in COVID-19 convalescents for 2 years after discharge. These results showed the persistent antibody-dependent immunity could protect against the WT and Delta variant to some extent. However, the Omicron variants (BA.1, BA.2, and BA.4/5) largely escaped this preexisting immunity in recovered individuals. Furthermore, we revealed that inactivated vaccines (BBIBP-CorV, CoronaVac, or KCONVAC) could improve the plasma neutralization and help to maintain the broadly neutralizing antibodies at a certain level. Notably, with the time-dependent decline of antibody, 1-dose or 2-dose vaccination strategy seemed not to be enough to provide immune protection against the emerging variants. Overall, these results facilitated our understanding of SARS-CoV-2-induced antibody memory, contributing to the development of immunization strategy against SARS-CoV-2 variants for such a large number of COVID-19 survivors.

Efficacy and Safety of a Booster Vaccination with Two Inactivated SARS-CoV-2 Vaccines on Symptomatic COVID-19 Infection in Adults: Results of a Double-Blind, Randomized, Placebo-Controlled, Phase 3 Trial in Abu Dhabi.

IMPORTANCE: The protective efficacy of COVID-19 vaccinations has declined over time such that booster doses are required. OBJECTIVE: To evaluate the efficacy and adverse events of booster doses of two inactivated COVID-19 vaccines. DESIGN: This is a double-blind, randomized, placebo-controlled phase 3 trial aiming to evaluate the protective efficacy, safety, and immunogenicity of inactivated SARS-CoV-2 vaccine (Vero cells) after inoculation with booster doses of inactivated COVID-19 vaccine. SETTING: Healthy volunteers were recruited in an earlier phase 3 trial of two doses of inactivated vaccine. The participants in Abu Dhabi maintained the blind state of the trial and received a booster dose of vaccine or placebo at least six months after the primary immunization. PARTICIPANTS: Adults aged 18 and older with no history of SARS-CoV, SARS-CoV-2, or Middle East respiratory syndrome infection (via onsite inquiry) were screened for eligibility. INTERVENTIONS: A total of 9370 volunteers were screened and randomly allocated, of which 61 voluntarily withdrew from the screening stage without booster inoculation; 9309 received the booster vaccination, with 3083 in the WIV04 group, 3150 in the HB02 group, and 3076 in the alum-only group. Further, 5µg and 4µg of inactivated SARS-CoV-2 virion was adsorbed into aluminum hydroxide in a 0.5 mL aqueous suspension for WIV04 and HB02 vaccines. MAIN OUTCOMES AND MEASURES: The primary efficacy outcome was the prevention of PCR-confirmed symptomatic COVID-19 from 14 days after the booster vaccine in the per-protocol population. A safety analysis was performed in the intention-to-treat population. RESULTS: Symptomatic COVID-19 was identified in 36 participants in the WIV04 group (9.9 [95% CI, 7.2-13.8] per 1000 person-years), 28 in the HB02 group (7.6 [95% CI, 5.2-11.0] per 1000 person-years), and 193 in the alum-only group (55.2 [95% CI, 47.9-63.5] per 1000 person-years), resulting in a vaccine efficacy of 82.0% (95% CI, 74.2-87.8%) for WIV04 and 86.3% (95% CI, 79.6-91.1%) for HB02. One severe case of COVID-19 occurred in the alum-only group, and none occurred in the vaccine groups. Adverse reactions within seven days after vaccination occurred in 29.4% to 34.3% of participants in the three groups. Serious adverse events were rare and not related to vaccines (WIV04: 17 [0.5%]; HB02: 11 [0.4%]; alum only: 40 [1.3%]). CONCLUSIONS AND RELEVANCE: This study evaluated the safety of the booster dose, which was well tolerated by participants. Booster doses given over six months after the completion of primary immunization can help to provide more-effective protection against COVID-19 in healthy people 18 years of age or older. At the same time, the anti-SARS-CoV-2 antibodies produced by the two groups of experimental vaccines exhibited extensive cross-neutralization against representative SARS-CoV-2 variants. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov (NCT04510207).

Significant neutralizing escapes of Omicron and its sublineages in SARS-CoV-2-infected individuals vaccinated with inactivated vaccines.

In China, most SARS-CoV-2-infected individuals had been vaccinated with inactivated vaccines. However, little is known about their immune resistances to the previous variants of concerns (VOCs) and the current Omicron sublineages. Here, we collected convalescent serum samples from SARS-CoV-2-infected individuals during the ancestral, Delta, and Omicron BA.1 waves, and evaluated their cross-neutralizing antibodies (nAbs) against the previous VOCs and the current Omicron sublineages using VSV-based pseudoviruses. In the convalescents who had been unvaccinated and vaccinated with two doses of inactivated vaccines, we found infections from either the ancestral or the Delta strain elicited moderate cross-nAbs to previous VOCs, but very few cross-nAbs to the Omicron sublineages, including BA.1, BA.2, BA.3, and BA.4/5. The individuals who had been vaccinated with two doses of inactivated vaccines before Omicron BA.1 infection had moderate nAbs to Omicron BA.1, but weak cross-nAbs to the other Omicron sublineages. While three doses of inactivated vaccines followed Omicron BA.1 infection induced elevated and still weak cross-nAbs to other Omicron sublineages. Our results indicate that the Omicron sublineages show significant immune escape in the previously SARS-CoV-2-infected individuals and thus highlights the importance of vaccine boosters in this population.

Clinical characteristics and severity of beta and delta variants of SARS-CoV-2 and the effect of vaccine on delta variants.

Background: The Delta variant of concern (VOC) is rapidly becoming the dominant strain globally. We report the clinical characteristics and severity of hospitalized patients infected with Delta and Beta VOCs during the local outbreak in Harbin, Heilongjiang Province, China, and the effect of vaccines on the Delta variant. Methods: We collected a total of 735 COVID-19 patients from the First Affiliated Hospital of Harbin Medical University, including 96 cases infected with the Delta VOC and 639 cases infected with the Beta VOC. Demographic, clinical characteristic and laboratory findings were collected and compared. Results: Differences in viral shedding, IgG and IgM levels, and the neutrophil-to-lymphocyte ratio were noted between the Delta and Beta VOCs (p < 0.05). Survival analysis of the two groups revealed longer viral shedding of the Delta VOC (p < 0.05). For the Delta VOC, the longer the vaccination period, the lower the IgG and IgM levels. IgM levels were higher in the convalescent plasma group, whereas lymphocyte counts were lower. Conclusions: Delta VOC virus shedding was longer compared with Beta VOC shedding. Vaccination with inactivated vaccines can reduce the severe illness rate of the Delta VOC. IgG and IgM levels are reduced as the time period between the first and second vaccine doses increases.

Immunogenicity profiling and distinct immune response in liver transplant recipients vaccinated with SARS-CoV-2 inactivated vaccines.

SARS-CoV-2 vaccination has been recommended for liver transplant (LT) recipients. However, our understanding of inactivated vaccine stimulation of the immune system in regulating humoral and cellular immunity among LT recipients is inadequate. Forty-six LT recipients who received two-dose inactivated vaccines according to the national vaccination schedule were enrolled. The clinical characteristics, antibody responses, single-cell peripheral immune profiling, and plasma cytokine/chemokine/growth factor levels were recorded. Sixteen (34.78%) LT recipients with positive neutralizing antibody (nAb) were present in the Type 1 group. Fourteen and 16 LT recipients with undetected nAb were present in the Type 2 and Type 3 groups, respectively. Time from transplant and lymphocyte count were different among the three groups. The levels of anti-RBD and anti-S1S2 decreased with decreasing neutralizing inhibition rates. Compared to the Type 2 and Type 3 groups, the Type 1 group had an enhanced innate immune response. The proportions of B, DNT, and CD3+CD19+ cells were increased in the Type 1 group, whereas monocytes and CD4+ T cells were decreased. High CD19, high CD8+CD45RA+ cells, and low effector memory CD4+/naïve CD4+ cells of the T-cell populations were present in the Type 1 group. The Type 1 group had higher concentrations of plasma CXCL10, MIP-1 beta, and TNF-alpha. No severe adverse events were reported in all LT recipients. We identified the immune responses induced by inactivated vaccines among LT recipients and provided insights into the identification of immunotypes associated with the responders.

Durability of antibodies post vaccination with two doses of inactivated BBIBP-CorV vaccine.

BACKGROUND: Breakthrough infections post-COVID-19 vaccination occur with the emerging variants of the SARS-CoV virus which might be either due to the newer variants escaping immune response or the waning of antibodies over time. However, there is lack of long-term follow-up evidence on the waning of immune response following inactivated COVID-19 vaccine. METHODS: A retrospective, observational study was conducted on serum samples of individuals who had received two doses of BBIBP-CorV vaccine. Individual's antibody responses were evaluated based on IgG anti-S and neutralizing antibodies measurements. Antibody samples were categorized into four groups, defined by the time interval from the individual's receipt of the BBIBP-CorV vaccine: <30 days, 30-90 days, 91-180 days and >180 days. RESULTS: A total of 6668 serum samples from inactivated BBIBP-CorV vaccine recipients were analyzed for IgG anti-S and neutralizing antibodies. 571 (8.6%) samples were tested during the first 29 days interval post vaccination, 3642 (54.6%) were tested during 30-90 days interval, 2173 (32.6%) samples were tested during 91 to 180 days interval and 282(4.2%) were tested at >180 days interval post vaccination. We found that more than 50% of the individuals had antibody titers below the average cut-off range at the 91-180 days interval post vaccination. Older age (>60 years), male gender, chronic kidney disease, hypertension, immunodeficiencies and increased interval post vaccination emerged as independent risk factors associated with lower immune response. CONCLUSION: Inactivated BBIBP-CorV vaccine recipients, based on age, gender and associated comorbid conditions might need booster doses at an earlier interval than the currently followed six months interval.

The immunogenicity of an inactivated vaccine against SARS-CoV-2 in healthy individuals: A systematic review and meta-analysis.

OBJECTIVE: Inactivated (killed) vaccines against COVID-19 have been widely used for the control of the pandemic condition. We performed a systematic and meta-analysis review of randomized, double-blind, placebo-controlled trials of the immunogenicity of inactivated vaccines against SARS-CoV-2 in healthy individuals. METHODS: In the present study, all research and evidence were extracted from the available online databases. Two researchers randomly evaluated the assessment of the research sensitivity. Finally, after quality assessment and regarding the specific inclusion and exclusion criteria, the eligible articles were entered for meta-analysis. The heterogeneity between the results of the studies was measured using test statistics (Cochran's Q) and the I2 index. The forest plots illustrated the point and pooled estimates with 95% confidence intervals (crossed lines). All statistical analyses were performed using Comprehensive meta-Analysis V.2 software. RESULTS: This meta-analysis included six primary studies investigating the immunogenicity of inactivated vaccines against SARS-CoV-2 in healthy individuals. According to the pooled prevalence (95% confidence interval), neutralizing antibody responses 28 days after receiving the second dose regarding different ages and micrograms per dose was 95.50% (CI: 93.2-97.1%). Our results showed that antibody levels were higher in the 6 µg group than in other groups. 98.3% (CI: 94.2-99.5%). CONCLUSION: Since the rapid development of vaccinations has sparked widespread public anxiety regarding vaccine efficacy. Governments and unvaccinated individuals, particularly those with vaccination reluctance, will be interested in and benefit from the findings of this systematic study.

Potential COVID -19 therapeutics in clinical trials - a brief review

The severe acute respiratory syndrome coronavirus 2 (SARS - CoV2), the causative viral pathogen of the COVID-19 pandemic belongs to the family of Coronaviruses which are positive single stranded RNA viruses. The scientific fraternity has developed and developing various types of vaccines for prevention against COVID-19, such as inactivated virus vaccines, mRNA vaccines, replicating vector protein subunit vaccines, etc., Out of which ten vaccines namely Novovax, Covovax (protein subunit vaccines), Pfizer BNT16b2, Moderna mRNA 1273 (mRNA vaccines), Johnson & Johnson Ad26, Cov2.S, Astrazeneca AZD1222, Covishield (non-replicating viral vector vaccines), Covaxin, Sinopharm BBIBP-CorV, CoronoVac (inactivated vaccines) have been approved for clinical use by WHO. There is an urgent need for SARS-CoV2 specific therapeutics for the treatment of COVID-19 as there is the emergence of various variants such as Alpha, Beta, Gamma, Delta, Omicron, etc. The emergence of variants that possesses immune evading property and spike protein mutation have increased infectivity and more pathogenicity which impelled the need to develop various therapeutics for the treatment of COVID-19. This review compiles the information about potential antiviral candidates in preclinical trials intended for the treatment of COVID-19. The clinical development of such antivirals will be very crucial for the treatment of COVID-19 and also to curb the spread as the present scenario depends on the development of effective prophylactic vaccines.

A cohort study on the immunogenicity and safety of the inactivated SARS-CoV-2 vaccine (BBIBP-CorV) in patients with breast cancer: does trastuzumab interfere with the outcome?

Background: The COVID-19 pandemic has led to more than 260 million infections and 55 million deaths as of early December 2021, worldwide. Vaccinating people against COVID-19 is considered as he best approach to overcome the pandemic since COVID 19-vaccines are effective and can reduce the risk of getting and spreading the virus. However, their efficacy and safety in patients with underlying disease such as cancers have not been approved yet. Here we report a cohort study on immunogenicity and safety of the inactivated SARS-CoV-2 vaccine (BBIBP-CorV) in patients with breast cancer, who were vaccinated as a part of a national plan for vaccination of patients with special diseases.

Effects of different mucosal adjuvants on the immune responses induced by porcine deltacoronavirus in mice

Objective: The aim of this study is to screen an ideal adjuvant for an inactivated porcine deltacoronavirus(PDCoV) vaccine to induce mucosal immunity and reduce the side effect of the vaccine. We used different mucosal adjuvants to prepare the inactivated PDCoV vaccines. We then used mouse model to evaluate the humoral, cellular and mucosal immune responses induced by the inactivated vaccines via different immunization routes.