Distinct Vaccine Efficacy Rates Among Health Care Workers During a COVID-19 Outbreak in Jordan

BACKGROUND: We aimed to assess the efficacy of 3 COVID-19 vaccines in a population of health care workers at a tertiary cancer center in Amman, Jordan. METHODS: We evaluated the records of 2855 employees who were fully vaccinated with 1 of 3 different vaccines and those of 140 employees who were not vaccinated. We measured the number of SARS-CoV-2 infections that occurred at least 14 days after the second vaccine dose. RESULTS The 100-day cumulative incidence of PCR-confirmed SARS-CoV-2 infections was 19.3% +/- 3.3% for unvaccinated employees and 1.7% +/- 0.27% for fully vaccinated employees. The 100-day cumulative infection rates were 0.7% +/- 0.22% in BNT162b2 vaccine recipients (n = 1714), 3.6% +/- 0.77% in BBIBP-CorV recipients (n = 680), and 2.3% +/- 0.73% in ChAdOx1 recipients (n = 456). We used Cox regression analyses to compare the risks of SARS-CoV-2 infection among the different vaccine recipient groups and found a significantly higher infection risk in BBIBP-CorV (hazard ratio [HR] = 2.9 +/- 0.31) and ChAdOx1 recipients (HR = 3.0 +/- 0.41) compared to BNT162b2 recipients (P = .00039 and .0074, respectively). Vaccinated employees who had no previously confirmed SARS-CoV-2 infections were at a markedly higher risk for breakthrough infections than those who experienced prior infections (HR = 5.7 +/- 0.73, P = .0178). CONCLUSIONS: Our study offers a real-world example of differential vaccine efficacy among a high-risk population during a national outbreak. We also show the important synergism between a previous SARS-CoV-2 infection and vaccination.

Venezuelan Equine Encephalitis Virus V3526 Vaccine RNA-Dependent RNA Polymerase Mutants Increase Vaccine Safety Through Restricted Tissue Tropism in a Mouse Model

Background: Venezuelan equine encephalitis virus (VEEV) is an arbovirus endemic to the Americas, for which no vaccines or antiviral agents have been approved. TC-83 and V3526 are the best-characterized vaccine candidates for VEEV. Both are live-attenuated vaccines and have been associated with safety concerns, although fewer concerns exist for V3526. A previous attempt to improve the TC-83 vaccine focused on further attenuating the vaccine by adding mutations that alter the error-incorporation rate of the RNA-dependent RNA polymerase (RdRp). Methods: The research herein examined the effects of these RdRp mutations in V3526 by cloning the 3X and 4X strains, assessing vaccine efficacy against challenge in adult female CD-1 mice, examining neutralizing-antibody titers, investigating vaccine tissue tropism, and testing the stability of the mutant strains. Results: The V3526 RdRp mutants exhibited less tissue tropism in the spleen and kidney than the wild-type V3526, while maintaining vaccine efficacy. Illumina sequencing indicated that the RdRp mutations reverted to wild-type V3526 after five passages in murine pup brains. Conclusions: The observed genotypic reversion is likely to be of limited concern, because wild-type V3526 remains an effective vaccine capable of providing protection. Our results indicate that the V3526 RdRp mutants may be a safer vaccine design than the original V3526.

Covid-19 disease dynamics with vaccination: The effect of uncertainty

Rate parameters are critical in estimating the covid burden using mathematical models. In the Covid-19 mathematical models, these parameters are assumed to be constant. However, uncertainties in these rate parameters are almost inevitable. In this paper, we study a stochastic epidemic model of the SARS-CoV-2 virus infection in the presence of vaccination in which some parameters fluctuate around its average value. Our analysis shows that if the stochastic basic reproduction number (SBRN) of the system is greater than unity, then there is a stationary distribution, implying the long-time disease persistence. A sufficient condition for disease eradication is also prescribed for which the exposed class goes extinct, followed by the infected class. The disease eradication criterion may not hold if the rate of vaccine-induced immunity loss increases or/and the force of infection increases. Using the Indian Covid-19 data, we estimated the model parameters and showed the future disease progression in the presence of vaccination. The disease extinction time is estimated under various conditions. It is revealed that the mean extinction time is an increasing function of both the force of infection and immunity loss rate and shows the lognormal distribution. We point out that disease eradication might not be possible even at a higher vaccination rate if the vaccine-induced immunity loss rate is high. Our observation thus indicates the endemicity of the disease for the existing vaccine efficacy. The disease eradication is possible only with a higher vaccine efficacy or a reduced infection rate.

SARS-CoV-2 variants genome analysis of Indonesian isolates and their responses to available vaccines

Background SARS-CoV-2 is a virus that initially appeared in Wuhan, China, at the end of 2019. Since then, the virus has spread until to almost all countries resulting in a global pandemic. Over time, this virus continues to mutate and produce several other variants. In Indonesia, there are multiple variants of SARS-CoV-2 identified, as well as various local variants that are not yet considered to be ‘variants of concern’. Therefore, this investigation is intended to understand the prevalence and epidemiology of the virus, along with detecting the mutations that occur in genes associated with whole-genome-sequences (WGS) isolated in Indonesia. Result Analyses were performed to investigate SARS-CoV-2 prevalence in Indonesia using data obtained from GISAID.org. A whole-genome sequencing was performed on the random samples taken from GISAID.org utilizing the BLAST tool from NCBI. The variants identified in Indonesia are Alpha, Beta and Delta variants, as well as local variants B.1.470 and B.1.466.2. As of the end of November, it was found that there are a total of 5.348 cases of the Delta, 78 cases of the Alpha, 22 cases of the Beta, 572 cases of the local variant B.1.470, and 1.833 cases of the local variant B.1.466.2. Other cases include 219 cases of local variant B.1.1.398, 160 cases of local variant B.1.459 and 1.028 cases of the wild type. In total there are 9.260 isolated genomes collected in GISAID that are located in Indonesia. Using BLAST, WGS of Alpha, Delta, Beta, B.1.470 and B.1.466.2 variants isolated in Indonesia was compared with the wild type from Wuhan NC.045512.2. It was found that multiple mutations have occurred in the samples. The mutations identified as are H69del, V70I, N501Y, D614G, A570D, P681H, T716I, S982A, and D1118H in the Alpha variant, T19R, L452R, T478K, D614G, and D950N in the Delta variant, D215G, D614G, A701V, L241-, L242-, K417N in the Beta variant, D614G, L242F, and S12F in the B.1.470 variant and D614G, N439K, and P681R in the B.1.466.2 variant. These mutations had caused alterations in the characteristics of the virus and how it may affect vaccine efficacy. Conclusions The results from whole-genome sequencing of variants isolated in Indonesia have found that multiple mutations have occurred in genes of the SARS-CoV-2 Virus and it caused alterations in the characteristics of the virus and may affect vaccine efficacy. It should be noted that classification from the GISAID website may change overtime. The result in this paper is based on the data taken at the end of November.

How to induce protective humoral immunity against Plasmodium falciparum circumsporozoite protein

The induction of protective humoral immune responses against sporozoite surface proteins of the human parasite Plasmodium falciparum (Pf) is a prime goal in the development of a preerythrocytic malaria vaccine. The most promising antibody target is circumsporozoite protein (CSP). Although PfCSP induces strong humoral immune responses upon vaccination, vaccine efficacy is overall limited and not durable. Here, we review recent efforts to gain a better molecular and cellular understanding of anti-PfCSP B cell responses in humans and discuss ways to overcome limitations in the induction of stable titers of high-affinity antibodies that might help to increase vaccine efficacy and promote long-lived protection.

Finally, an FDA Approval for an Immunization Against COVID-19: Hope on the Horizon

Objective Coronavirus disease 2019 (COVID-19) is a respiratory infection known as severe respiratory acute syndrome coronavirus 2 (SARS-CoV-2). The purpose of this manuscript is to review information leading to the Food and Drug Administration (FDA) approval of the Pfizer-BioNTech COVID-19 Vaccine. Data Sources A literature search was conducted of PubMed and clinicaltrials.gov (August 2018—October 2021) to identify trials related to the FDA approval of Pfizer-BioNTech COVID-19 Vaccine. Study selection and data extraction Trials included are those the FDA deemed significant and accurate enough to be included in the FDA approval process. Information not recognized by the Centers of Disease Control and Prevention (CDC) nor FDA is omitted to not add to further confusion and misinformation. Data synthesis In persons 16 years or older without evidence of prior SARS-CoV-2 infection, a total of 77 COVID-19 cases (0.39%) in the vaccine group from 7 days onward after the second dose vs 833 (4.1%) in the placebo group (Vaccine efficacy 91.1%; 95% confidence interval [CI]: 88.8-93.1). According the CDC definition of severe infection, there were no severe infections in the vaccine group 7 days and onward after the second dose, compared to 31 (0.15%) in the placebo group (Vaccine efficacy 100%; 95% CI: 87.6-100.0). Relevance to Patient Care and Clinical Practice: Reduction of infection by SARS-COV-2 is a top priority in protecting the health of all people and the official approval of the Pfizer-BioNTech vaccination may improve this goal. Conclusions Data available show a high efficacy rate of preventing SARS -CoV-2 with relatively low rates of ADE after full vaccination with Pfizer-BioNTech COVID-19 vaccine.

Modelling COVID-19 Vaccine Breakthrough Infections in Highly Vaccinated Israel - the effects of waning immunity and third vaccination dose

In August 2021, a major wave of the SARS-CoV-2 Delta variant erupted in the highly vaccinated population of Israel. The Delta variant has a transmission advantage over the Alpha variant, and thus replaced it in approximately two months. The outbreak led to an unexpectedly large proportion of breakthrough infections (BTI)-- a phenomenon that received worldwide attention. The BTI proportion amongst cases in the age group of 60+ years reached levels as high as ~85% in August 2021. Most of the Israeli population, especially those 60+ age, received their second dose of the vaccination, four months before the invasion of the Delta variant. Hence, either the vaccine induced immunity dropped significantly or the Delta variant possesses immunity escaping abilities. In this work, we analyzed and model age-structured cases, vaccination coverage, and vaccine BTI data obtained from the Israeli Ministry of Health, to help understand the epidemiological factors involved in the outbreak. We propose a mathematical model which captures a multitude of factors, including age structure, the time varying vaccine efficacy, time varying transmission rate, BTIs, reduced susceptibility and infectivity of vaccinated individuals, protection duration of the vaccine induced immunity, and the vaccine distribution. We fitted our model to the cases among vaccinated and unvaccinated, for <60 and 60+ age groups, to address the aforementioned factors. We found that the transmission rate was driven by multiple factors including the invasion of Delta variant and the mitigation measures. Through a model reconstruction of the reproductive number R0(t), it was found that the peak transmission rate of the Delta variant was 1.96 times larger than the previous Alpha variant. The model estimated that the vaccine efficacy dropped significantly from >90% to ~40% over 6 months, and that the immunity protection duration has a peaked Gamma distribution (rather than exponential). We further performed model simulations quantifying the important role of the third vaccination booster dose in reducing the levels of breakthrough infections. This allowed us to explore "what if" scenarios should the booster not have been rolled out. Application of this framework upon invasion of new pathogens, or variants of concern, can help elucidate important factors in the outbreak dynamics and highlight potential routes of action to mitigate their spread.

The Bovine Tuberculoid Granuloma

The bovine tuberculoid granuloma is the hallmark lesion of bovine tuberculosis (bTB) due to Mycobacterium bovis infection. The pathogenesis of bTB, and thereby the process of bovine tuberculoid granuloma development, involves the recruitment, activation, and maintenance of cells under the influence of antigen, cytokines and chemokines in affected lungs and regional lymph nodes. The granuloma is key to successful control of bTB by preventing pathogen dissemination through containment by cellular and fibrotic layers. Paradoxically, however, it may also provide a niche for bacterial replication. The morphologic and cellular characteristics of granulomas have been used to gauge disease severity in bTB pathogenesis and vaccine efficacy studies. As such, it is critical to understand the complex mechanisms behind granuloma initiation, development, and maintenance.