Trait-Based Vaccination of Individual Meerkats (Suricata suricatta) against Tuberculosis Provides Evidence to Support Targeted Disease Control

Individuals vary in their potential to acquire and transmit infections, but this fact is currently underexploited in disease control strategies. We trialled a trait-based vaccination strategy to reduce tuberculosis in free-living meerkats by targeting high-contact meerkats (socially dominant individuals) in one study arm, and high-susceptibility individuals (young subordinates) in a second arm. We monitored infection within vaccinated groups over two years comparing the results with untreated control groups. Being a member of a high-contact group had a protective effect on individuals’ survival times (Hazard Ratio = 0.5, 95% Confidence Interval, CI: 0.29–0.88, p = 0.02) compared to control groups. Over the study, odds of testing positive for tuberculosis increased more than five-fold in control groups (Odds Ratio = 5.40, 95% CI = 0.94–30.98, p = 0.058); however, no increases were observed in either of the treatment arms. Targeted disease control approaches, such as the one described in this study, allow for reduced numbers of interventions. Here, trait-based vaccination was associated with reduced infection rates and thus has the potential to offer more efficient alternatives to traditional mass-vaccination policies. Such improvements in efficiency warrant further study and could make infectious disease control more practically achievable in both animal (particularly wildlife) and human populations.

Machine learning for emerging infectious disease field responses

Emerging infectious diseases (EIDs), including the latest COVID-19 pandemic, have emerged and raised global public health crises in recent decades. Without existing protective immunity, an EID may spread rapidly and cause mass casualties in a very short time. Therefore, it is imperative to identify cases with risk of disease progression for the optimized allocation of medical resources in case medical facilities are overwhelmed with a flood of patients. This study has aimed to cope with this challenge from the aspect of preventive medicine by exploiting machine learning technologies. The study has been based on 83,227 hospital admissions with influenza-like illness and we analysed the risk effects of 19 comorbidities along with age and gender for severe illness or mortality risk. The experimental results revealed that the decision rules derived from the machine learning based prediction models can provide valuable guidelines for the healthcare policy makers to develop an effective vaccination strategy. Furthermore, in case the healthcare facilities are overwhelmed by patients with EID, which frequently occurred in the recent COVID-19 pandemic, the frontline physicians can incorporate the proposed prediction models to triage patients suffering minor symptoms without laboratory tests, which may become scarce during an EID disaster. In conclusion, our study has demonstrated an effective approach to exploit machine learning technologies to cope with the challenges faced during the outbreak of an EID.

VarLOCK - sequencing independent, rapid detection of SARS-CoV-2 variants of concern for point-of-care testing, qPCR pipelines and national wastewater surveillance

The COVID-19 pandemic continues to pose a threat to the general population. The ongoing vaccination programs provide protection to individuals and facilitate the opening of society and a return to normality. However, emergent and existing SARS-CoV-2 variants capable of evading the immune system endanger the efficacy of the vaccination strategy. To preserve the efficacy of SARS-CoV-2 vaccination globally, aggressive and effective surveillance for known and emerging SARS-CoV-2 Variants of Concern (VOC) is required. Rapid and specific molecular diagnostics can provide speed and coverage advantages compared to genomic sequencing alone, benefitting the public health response and facilitating VOC containment. In this work, we expand the recently developed SARS-CoV-2 CRISPR-Cas detection technology (SHERLOCK) to allow rapid and sensitive discrimination of VOCs, that can be used at point of care and/or implemented in the pipelines of small or large testing facilities, and even determine proportion of VOCs in pooled population-level wastewater samples. This technology aims to complement the ongoing sequencing efforts to allow facile and, crucially, rapid identification of individuals infected with VOCs to help break infection chains. Here, we show the optimisation of our VarLOCK assays (Variant-specific SHERLOCK) for multiple specific mutations in the S gene of SARS-CoV-2 and validation with samples from the Cardiff University Testing Service. We also show the applicability of VarLOCK to national wastewater surveillance of SARS-CoV-2 variants. In addition, we show the rapid adaptability of the technique for new and emerging VOCs such as Omicron.

Acceptance of COVID-19 Vaccine A mong Residents of South India: A Cross-sectional Survey

Background COVID-19 vaccines provide concrete hope of mitigating the spread of the virus and enabling countries worldwide to resume financial and social activities disrupted by the pandemic. Several COVID 19 vaccines have already received approval from regulatory bodies across the world, the vaccine roll out has started and many countries are implementing mass vaccination campaigns. This study aims to evaluate the acceptability of COVID-19 vaccines and its predictors, along with the attitudes towards the vaccines among the general population of South India. Materials and Methods This study was conducted as an online survey during December 2020 and January 2021. A Self-administered pre-tested questionnaire was used for the survey. Excel 2019 and SPPS 24 were used for statistical analysis. Descriptive statistics were used, and a Chi-square test was performed. Results A total of 686 people have participated in this study, with a mean age of 30.4 years. 30.9% of study participants have already been infected with COVID-19. 76.2% responded 'yes' for accepting the COVID-19 vaccine, 69% responded to prefer 'routine' administration of the vaccine, and 50.1% were likely to take the COVID-19 vaccine 'as soon as possible' once available. Conclusion Public health authorities and policymakers need to streamline systematic interventions and awareness campaigns to improve the acceptance of COVID 19 vaccines and reduce vaccine hesitancy levels. Vaccination strategy should be targeted at the specific needs and attitudes of the concerned population. Reviving the trust in the vaccination procedures and outcomes and offering transparent information regarding the vaccines' efficacy and safety seem to be particularly importance for the population of our study.

Seroprevalence Study of Pertussis in Adults at Childbearing Age and Young Infants Reveals the Necessity of Booster Immunizations in Adults in China

In China, the vaccination strategy against pertussis is started from 3 months of age, with no booster dose used after the booster given at two years. Despite a high vaccination coverage, pertussis has been increasingly reported since the last decade. This study evaluates the prevalence of serum anti-pertussis toxin (PT) IgG antibodies in adults at childbearing age and infants before the age of primary immunization in Beijing, China. A total of 1175 serum samples randomly selected from individuals who attended an annual health examination at the Sixth Medical Center of the PLA General Hospital, Beijing, in 2019, was included. The geometric mean concentration (GMC) and median concentration of anti-PT IgG antibodies among adults aged 20–39 years were 3.81 IU/mL and 3.24 IU/mL, and the corresponding concentrations were 1.72 IU/mL and 1.43 IU/mL among infants under 3 months of age. The seroprevalence of PT IgG antibodies ≥ 40 IU/mL in adults and infants was 2.0% (15/735) and 1.1% (5/440). In total, 65.99% (485/735) of adults and 83.41% (367/440) of infants had non-detectable pertussis-specific antibodies (<5 IU/mL). Our results showed that the majority of adults at a reproductive age and young infants are vulnerable to pertussis, suggesting that booster vaccinations in adults should be considered in this country.

Surveillance of SARS-CoV-2 antibodies of patients in the local affected area during Wuhan lockdown

Background Serosurveillance is crucial in estimating the range of SARS-CoV-2 infections, predicting the possibility of another wave, and deciding on a vaccination strategy. To understand the herd immunity after the COVID-19 pandemic, the seroprevalence was measured in 3062 individuals with or without COVID-19 from the clinic. Methods The levels of SARS-CoV-2 antibody IgM and IgG were measured by the immuno-colloidal gold method. A fusion fragment of nucleocapsid and spike protein was detected by a qualitative test kit with sensitivity (89%) and specificity (98%). Results The seroprevalence rate for IgM and IgG in all outpatients was 2.81% and 7.51%, respectively. The sex-related prevalence rate of IgG was significantly higher (P < 0.05) in women than men. The highest positive rate of IgM was observed in individuals < 20 years of age (3.57%), while the highest seroprevalence for IgG was observed in persons > 60 years of age (8.61%). Positive rates of IgM and IgG in the convalescent patients were 31.82% and 77.27%, respectively, which was significantly higher than individuals with suspected syndromes or individuals without any clinical signs (P < 0.01). Seroprevalence for IgG in medical staff was markedly higher than those in residents. No significant difference of seroprevalence was found among patients with different comorbidities (P > 0.05). Conclusions The low positive rate of the SARS-CoV-2 IgM and nucleic acid (NA) test indicated that the SARS-CoV-2 outbreak is subsiding after 3 months, and the possibility of reintroduction of the virus from an unidentified natural reservoir is low. Seroprevalence provides information for humoral immunity and vaccine in the future.

Immunogenicity of a Heterologous Prime-Boost COVID-19 Vaccination with mRNA and Inactivated Virus Vaccines Compared with Homologous Vaccination Strategy against SARS-CoV-2 Variants

The emergence of SARS-CoV-2 variants may impact the effectiveness of vaccines, while heterologous vaccine strategy is considered to provide better protection. The immunogenicity of an mRNA-inactivated virus vaccine against the SARS-CoV-2 wild-type (WT) and variants was evaluated in the study. SARS-CoV-2 naïve adults (n = 123) were recruited and placed in the following groups: BNT162b2, CoronaVac or BNT162b2-CoronaVac (Combo) Group. Blood samples were collected to measure neutralization antibodies (NAb) by a live virus microneutralization assay (vMN) and surrogate NAb test. The day 56 vMN geometric mean titre (GMT) was 26.2 [95% confident interval (CI), [22.3–30.9] for Combo, 136.9 (95% CI, 104.2–179.7) for BNT162b2, and 14.7 (95% CI, 11.6–18.6) for CoronaVac groups. At 6 months post-first dose, the GMT declined to 8.0, 28.8 and 7.1 in the Combo, BNT162b2 and CoronaVac groups, respectively. Three groups showed reduced neutralizing activity against D614G, beta, theta and delta variants. At day 56 GMT (74.6) and month 6 GMT (22.7), the delta variant in the BNT162b2 group was higher than that in the Combo (day 56, 7.4; month 6, 5.5) and CoronaVac groups (day 56, 8.0; month 6, 5) (p < 0.0001). Furthermore, the mean surrogate NAb value on day 56 in the BNT162b2 group was 594.7 AU/mL and higher than 40.5 AU/mL in Combo and 38.8 AU/mL in CoronaVac groups (p < 0.0001). None of the participants developed severe adverse events, and all other adverse events were self-limiting. The Combo vaccination strategy was safe. The overall vaccine immunogenicity at day 56 and 6 months were comparable to the homologous CoronaVac group but inferior to the homologous BNT162b2 group, against both the WT and all variants. Furthermore, the antibody response of vaccines waned at 6 months and thereby, a third dose of the vaccine is needed for these vaccines.

Seven-Month Analysis of Five SARS-CoV-2 Antibody Assay Results after ChAdOx1 nCoV-19 Vaccination: Significant Decrease in SARS-CoV-2 Antibody Titer

We investigated the longevity rates of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after a complete ChAdOx1 nCoV-19 vaccination, which are rare and important to estimate their efficacy and establish a vaccination strategy. We assessed the positivity rates and changes of titers before (T0) and at one month (T1), four months (T2), and seven months (T3) after a ChAdOx1 nCoV-19 vaccination using five SARS-CoV-2 antibody assays. A total of 874 serum samples were obtained from 228 (T0 and T1), 218 (T2), and 200 (T3) healthcare workers. The positive rates for all five assays were 0.0–0.9% at T0, 66.2–92.5% at T1, 98.2–100.0% at T2, and 66.0–100.0% at T3. The positive rates at T3 were decreased compared to those at T2. The median antibody titers of all the assays at T3 were significantly decreased compared to those at T2 (860.5 to 232.0 U/mL for Roche total, 1041.5 to 325.5 AU/mL for Abbott IgG, 10.9 to 2.3 index for Siemens IgG, 99.5% to 94.7% for SD Biosensor V1, and 88.5% to 38.2% for GenScript). A third-dose scheme can be considered based on our data generated from five representative assays. Our findings contribute insights into SARS-CoV-2 antibody assays and appropriate vaccination strategies.

Attenuated replication and pathogenesis of SARS-CoV-2 B.1.1.529 Omicron

SARS-CoV-2 Omicron emerged in November 2021 and is rapidly spreading among the human populations. The variant contains 34 changes in its spike protein including 15 substitutions at the receptor-binding domain (RBD). While recent reports reveal that the Omicron variant can robustly escape from vaccine and therapeutic neutralization antibodies, the pathogenicity of the virus remains unknown. Here, we investigate the virological features and pathogenesis of the Omicron variant using in vitro and in vivo models. Our results demonstrate that the replication of the Omicron variant is dramatically attenuated in Calu3 and Caco2 but not in VeroE6 cells. Further mechanistic investigations reveal that the Omicron variant is deficient in transmembrane serine protease 2 (TMPRSS2) usage in comparison to that of WT, Alpha, Beta, and Delta variant, which explained its inefficient replication in Calu3 and Caco2 cells. Importantly, the replication of the Omicron variant is markedly attenuated in both the upper and lower respiratory tract of infected K18-hACE2 mice in comparison to that of WT and Delta variant, which results in its dramatically ameliorated lung pathology. When compared with SARS-CoV-2 WT, Alpha, Beta, and Delta variant, infection by the Omicron variant causes the least body weight loss and mortality rate. Overall, our study demonstrates that the Omicron variant is significantly attenuated in virus replication and pathogenicity in comparison with WT and previous variants. Our data suggest the current global vaccination strategy has forced SARS-CoV-2 into a new evolutionary trajectory towards reduced replication fitness in exchange of better immune escape. These findings are critical for setting policy in the pandemic control and disease management of COVID-19.