Waning Of Immunity Research Articles

Evaluating vaccine allocation strategies using simulation-assisted causal modeling

We develop a model to retrospectively evaluate age-dependent counterfactual vaccine allocation strategies against the coronavirus disease 2019 (COVID-19) pandemic. To estimate the effect of allocation on the expected severe-case incidence, we employ a simulation-assisted causal modeling approach that combines a compartmental infection-dynamics simulation, a coarse-grained causal model, and literature estimates for immunity waning. We compare Israel's strategy, implemented in 2021, with counterfactual strategies such as no prioritization, prioritization of younger age groups, or a strict risk-ranked approach; we find that Israel's implemented strategy was indeed highly effective. We also study the impact of increasing vaccine uptake for given age groups. Because of its modular structure, our model can easily be adapted to study future pandemics. We demonstrate this by simulating a pandemic with characteristics of the Spanish flu. Our approach helps evaluate vaccination strategies under the complex interplay of core epidemic factors, including age-dependent risk profiles, immunity waning, vaccine availability, and spreading rates.

Accelerated waning of the humoral response to COVID-19 vaccines in obesity

Obesity is associated with an increased risk of severe Coronavirus Disease 2019 (COVID-19) infection and mortality. COVID-19 vaccines reduce the risk of serious COVID-19 outcomes; however, their effectiveness in people with obesity is incompletely understood. We studied the relationship among body mass index (BMI), hospitalization and mortality due to COVID-19 among 3.6 million people in Scotland using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) surveillance platform. We found that vaccinated individuals with severe obesity (BMI > 40 kg/m2) were 76% more likely to experience hospitalization or death from COVID-19 (adjusted rate ratio of 1.76 (95% confidence interval (CI), 1.60–1.94). We also conducted a prospective longitudinal study of a cohort of 28 individuals with severe obesity compared to 41 control individuals with normal BMI (BMI 18.5–24.9 kg/m2). We found that 55% of individuals with severe obesity had unquantifiable titers of neutralizing antibody against authentic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus compared to 12% of individuals with normal BMI (P = 0.0003) 6 months after their second vaccine dose. Furthermore, we observed that, for individuals with severe obesity, at any given anti-spike and anti-receptor-binding domain (RBD) antibody level, neutralizing capacity was lower than that of individuals with a normal BMI. Neutralizing capacity was restored by a third dose of vaccine but again declined more rapidly in people with severe obesity. We demonstrate that waning of COVID-19 vaccine-induced humoral immunity is accelerated in individuals with severe obesity. As obesity is associated with increased hospitalization and mortality from breakthrough infections, our findings have implications for vaccine prioritization policies.

The role of immune boosting and waning in shaping dengue epidemic dynamics.

Abstract Infection with one of the four dengue viruses (DENV1-4) induces both virus-specific and broadly reactive antibodies that may either provide protection or increase the severity of disease during secondary infection. Re-exposure in those with multiple prior DENV infections may boost immunity and reduce dengue risk and transmission; however, longitudinal studies investigating re-exposure and protective immunity for dengue epidemic dynamics are still lacking. For instance, does the interaction between long-term waning of immunity between infections and re-exposure to DENV or Zika virus (ZIKV) contribute to the epidemic periodicity? Since measuring re-exposure in highly immune individuals is difficult, previous studies have explored the role of boosting in protection against dengue disease but not using longitudinal measures of herd immunity. Here, we utilize both a longitudinal dataset of antibody titers to DENV and ZIKV measured annually in a Nicaraguan cohort from 2004–2021 and a mathematical model incorporating individual antibody boosting, antibody-dependent enhancement and waning to study the role of boosting on dengue transmission dynamics. Our results support our hypothesis that boosts in highly immune individuals contribute to herd immunity, delaying their contribution into the susceptibles and lowering the rate of dengue cases in future epidemics. However, as their immunity wanes due to lower transmission intensity, the susceptible fraction builds up until a major epidemic that includes re-infection of those with high titers. Our study highlights the interaction of immune boosting and waning in highly exposed adults in shaping dengue epidemics and inform vaccine efforts to maintain immunity over the life-course. Supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health & by grants from NIH (P01AI106695)

Prevalence and characteristics of COVID-19 vaccine breakthrough infection in Upper Egypt

BackgroundInfection breakthrough after COVID-19 vaccination is a point of conflict in current literature not only because of the estimation of the potential hazards and symptoms severity but also due to establishing a vaccination policy and measuring the extent of immunity after vaccination in addition to the waning of the humoral immunity over time. To our knowledge, this is the first study to stratify the risk of post-COVID-19 vaccination breakthroughs in Upper Egypt.MethodsIn this cross-sectional observational study, we enrolled 369 vaccinated patients registered in our facility either admitted or in out-patient clinic. Patients were interviewed and any proven history of COVID-19 infection after vaccination was recorded.ResultsIn the current study, 18.97% (70 patients) of the 369 subjects enrolled in the study had COVID-19breakthrough infection. Students were the high-risk group representing 18.6% of the study subjects. Hypertension, diabetes, and cardiac disease were the most comorbidities associated with a prevalence of 15.7%, 8.6%, and 4.3% respectively. Prior to COVID-19, confirmed infection was present in 42.9% of the study group. Fever, headache, myalgia, and cough were among the most common symptoms of the post-COVID vaccination breakthrough with a prevalence of 90%, 75.7%, 84.3%, and 74.3% respectively.ConclusionBreakthrough infection after COVID-19 vaccination is not uncommon. Most cases are mild and don’t require hospitalization. All types of vaccines tested in the current study offer adequate immunity and guard against severe COVID-19 infection. We encourage the current global policy of full vaccination.Trial registrationClinicalTrials.gov. NCT05033834. Registered September 5, 2021. COVID-19 Infection in After Vaccination-Full Text View-ClinicalTrials.gov.

Changes in Population Immunity Against Infection and Severe Disease From Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variants in the United States Between December 2021 and November 2022.

Although a substantial fraction of the US population was infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during December 2021-February 2022, the subsequent evolution of population immunity reflects the competing influences of waning protection over time and acquisition or restoration of immunity through additional infections and vaccinations. Using a Bayesian evidence synthesis model of reported coronavirus disease 2019 (COVID-19) data (diagnoses, hospitalizations), vaccinations, and waning patterns for vaccine- and infection-acquired immunity, we estimate population immunity against infection and severe disease from SARS-CoV-2 Omicron variants in the United States, by location (national, state, county) and week. By 9 November 2022, 97% (95%-99%) of the US population were estimated to have prior immunological exposure to SARS-CoV-2. Between 1 December 2021 and 9 November 2022, protection against a new Omicron infection rose from 22% (21%-23%) to 63% (51%-75%) nationally, and protection against an Omicron infection leading to severe disease increased from 61% (59%-64%) to 89% (83%-92%). Increasing first booster uptake to 55% in all states (current US coverage: 34%) and second booster uptake to 22% (current US coverage: 11%) would increase protection against infection by 4.5 percentage points (2.4-7.2) and protection against severe disease by 1.1 percentage points (1.0-1.5). Effective protection against SARS-CoV-2 infection and severe disease in November 2022 was substantially higher than in December 2021. Despite this high level of protection, a more transmissible or immune evading (sub)variant, changes in behavior, or ongoing waning of immunity could lead to a new SARS-CoV-2 wave.

Social dilemma analysis on vaccination game accounting for the effect of immunity waning

A new SEIRS-based ODE (Ordinary Differential Equation) model is built, where asymptomatic and symptomatic infectious compartments, hospitalized state and immune state are additionally introduced, which is dovetailed with a behavior model that defines the vaccination rate as time-variable. We also apply Social Efficiency Deficit; SED, to quantitatively identify whether or not social dilemma taking place behind the model dynamics. Numerical results prove that, depending on the fraction of asymptomatic infected individuals and the discount ratio of infected force for asymptomatic state compared with that for symptomatic one, whether or not social dilemma appearing is different, which is also substantially affected by the vaccination cost and the immunity waning rate. The behavior model tends to incur a slight social dilemma brought by wasting vaccination even in the region of disease free, identified by R0<1. Meanwhile, a relatively strong social dilemma is indicated in the parameter region where the behavior model shows less amount of vaccinated population while the social optimal state needs much more vaccinated for complete remission of disease.

A nested model with boosting and waning of immunity from Tilapia Lake Virus infection with distributed resistance to pathogens carrier-state.

This paper proposes and analyzes an immune-structured population model of tilapia subject to Tilapia Lake Virus (TiLV) disease. The model incorporates within-host dynamics, used to describe the interaction between the pathogen, the immune system and the waning of immunity. Individuals infected with a low dose acquire a low immunity level and those infected with a high dose acquire a high level of immunity. Since individuals' immune status plays an important role in the spread of infectious diseases at the population level, the within-host dynamics are connected to the between-host dynamics in the population. We define an explicit formula for the reproductive number [Formula: see text] and show that the disease-free equilibrium is locally asymptotically stable when [Formula: see text], while it is unstable when [Formula: see text]. Furthermore, we prove that an endemic equilibrium exists. We also study the influence of the initial distribution of host resistance on the spread of the disease, and find that hosts' initial resistance plays a crucial role in the disease dynamics. This suggests that the genetic selection aiming to improve hosts' initial resistance to TiLV could help fight the disease. The results also point out the crucial role played by the inoculum size. We find that the higher the initial inoculum size, the faster the dynamics of infection. Moreover, if the initial inoculum size is below a certain threshold, it may not result in an outbreak at the between-host level. Finally, the model shows that there is a strong negative correlation between heterogeneity and the probability of pathogen invasion.

Monkeypox (Mpox) outbreak during COVID-19 pandemic-Past and the future.

Monkeypox infection (Mpox) is caused by the Orthopoxvirus (OPXV) genus of the Poxviridae family, closely resembling its more famous sibling smallpox. Recently World Health Organization (WHO), have renamed monkeypox as Mpox citing racial concerns, so we will be referring to monkeypox as Mpox. There has been a recent outbreak in May 2022 when Mpox cases were identified in all six WHO regions. On July 23, 2022, WHO declared it a public health emergency. Before the current outbreak, Mpox had been reported in people from several parts of central and west African countries; and almost all Mpox cases in people outside of Africa were linked to international travel to countries where the disease commonly occurs or through imported animals. With the waning of smallpox vaccine-induced immunity, Mpox can spread in the global population. Though the virus generally does not cause high mortality in immunocompetent individuals, however, severe disease and mortality may result if the virus spreads to immunocompromised individuals, children, elderly individuals, pregnant women, and individuals living with comorbidities such as diabetes. The current transmission was suspected to have occurred through sexual activity in 95% of the persons with infection. It was found that 98% of the persons with infection were either gay or bisexual men, with 41% suffering from HIV infection. The reasons behind this current epidemiological behavior have to be studied further to formulate a hypothesis that, is it the homosexuals who need to be more concerned or is it a global concern, and is monkeypox changing its behaviour toa sexually transmitted infection? The rash, along with associated lymphadenopathy, is a clue toward Mpox infection, but polymerase chain reaction is needed for the confirmative diagnosis. With the discovery of a vaccine, repurposed antivirals, and precautionary steps to prevent the spread of infection, it might help in the containment of the virus. In addition, what we already know about Mpox has to be re-evaluated, because most of the information gathered is from low-resource settings in Africa. The world at large and health care agencies specifically needs to galvanize a well-funded global plan and research initiatives to contain the spread of Mpox. In this article, we have attempted to make the readers aware of the biology, etiopathogenesis including the changes at the cellular level the virus is causing, the changing trends of the virus transmission, and the clinical manifestations. We have also attempted to elaborate on the potential challenges and the need for early diagnosis and containment of this Mpox outbreak. This could be achieved by effectieve use of vaccination and taking social safety measures, especially by the communities at risk.

A Sensitive Public Health Issue-The Vaccine Acceptancy and the Anti-Pertussis Immune Status of Pregnant Women from a Romanian Metropolitan Area.

(1) Background: Immunization of pregnant women (PWs) against Bordetella pertussis infection is still a challenging health matter. (2) Methods: We gathered questionnaire data from 180 PWs regarding their expectancies and current opinion on infectious disease prevention. For the group of PWs who agreed to further investigations, the serum levels of Ig G anti-B. pertussis antibodies (IgG-PT) titer were measured and analyzed. (3) Results: A total of 180 PWs completed the questionnaire and 98 (54.44%, study group) accepted to perform the laboratory tests. During the first two pregnancy trimesters, PWs were found to be more willing (compared with the control group) to test for identifying high-risk situations that could affect themselves and their future infant (p < 0.001). Most of the participating PWs (91, 91.9%) had low levels of anti-pertussis antibodies (values < 40 IU/mL). Declared vaccine coverage of the PWs newborn infants for DTaP-1 and Prevenar 13 (at 2 months) and DTaP-2 and Prevenar 13 (at 4 months) vaccination reached 100% in the study group, while in the control group only 30/82 (36.59%) PWs accepted to be vaccinated during pregnancy, none of them providing data on their infants' vaccine coverage. (4) Conclusions: Enrolled PWs faced a waning immunity against the B. pertussis infection. By raising maternal confidence in the protective role of vaccines against infectious diseases, better vaccine acceptance and better infant vaccine coverage can be achieved.

Computer-Aided Discovery of Potent Broad-Spectrum Vaccine Adjuvants.

Adjuvants stimulate the immune system to vigorously respond to a vaccine. While current adjuvants such as aluminum salts and oil-in-water emulsions have been used for decades, they do not generate broad and long-lasting responses in many vaccines. Consequently, more potent adjuvants are needed. Here, using computer-aided molecule design and machine learning, we discovered 2 new, broad-spectrum adjuvants that can boost vaccine responses. Our library containing 46 toll-like receptor (TLR)-targeting agonist ligands were assembled on Au nanoparticles. Comprehensive in vitro, ex vivo and in vivo studies showed both leads promoted dendritic cell activation via multiple TLRs and enhanced antigen presentation to T cells. When used together with tumor-specific antigens to immunize mice against B16-OVA melanoma and 4T1-PD1 breast cancer, both adjuvants unleashed strong immune responses that suppressed tumor growth and lung metastases. Our results show computer-aided design and screening can rapidly uncover potent adjuvants for tackling waning immunity in current vaccines.

Computer‐Aided Discovery of Potent Broad‐Spectrum Vaccine Adjuvants

AbstractAdjuvants stimulate the immune system to vigorously respond to a vaccine. While current adjuvants such as aluminum salts and oil‐in‐water emulsions have been used for decades, they do not generate broad and long‐lasting responses in many vaccines. Consequently, more potent adjuvants are needed. Here, using computer‐aided molecule design and machine learning, we discovered 2 new, broad‐spectrum adjuvants that can boost vaccine responses. Our library containing 46 toll‐like receptor (TLR)‐targeting agonist ligands were assembled on Au nanoparticles. Comprehensive in vitro, ex vivo and in vivo studies showed both leads promoted dendritic cell activation via multiple TLRs and enhanced antigen presentation to T cells. When used together with tumor‐specific antigens to immunize mice against B16‐OVA melanoma and 4T1‐PD1 breast cancer, both adjuvants unleashed strong immune responses that suppressed tumor growth and lung metastases. Our results show computer‐aided design and screening can rapidly uncover potent adjuvants for tackling waning immunity in current vaccines.

Protective immunity of SARS-CoV-2 infection and vaccines against medically attended symptomatic omicron BA.4, BA.5, and XBB reinfections in Singapore: a national cohort study

Despite a large proportion of the population having been vaccinated and infected, Singapore had SARS-CoV-2 waves driven by the BA.5 and XBB sublineages of the omicron (B.1.1.529) variant. Data on the protective immunity against medically attended, symptomatic reinfections with omicron BA.4, BA.5, and XBB conferred by previous SARS-CoV-2 infections and vaccinations are scarce. We therefore aimed to derive information from Singapore's experience as one of the first countries with an XBB-driven wave. For this retrospective national cohort study, we used information from official databases of the Ministry of Health of Singapore to assess hybrid immunity (obtained from previous infection and vaccination) against medically attended, symptomatic BA.4 and BA.5 reinfections from Oct 1, 2022, to Nov 1, 2022, and medically attended, symptomatic XBB reinfections from Oct 18, 2022, to Nov 1, 2022, among Singapore citizens and permanent residents aged at least 18 years. All individuals with acute respiratory symptoms who presented at any health-care facility in Singapore between the stated dates were tested for SARS-CoV-2. Individuals were grouped into SARS-CoV-2-naive, pre-omicron, omicron BA.1, and omicron BA.2 groups according to their previous infection status. Data were also stratified by time from first infection to analyse the waning of immunity. Incidence rate ratios (IRRs) were measured by generalised linear Poisson regressions, with SARS-CoV-2-naive individuals as the reference group, and protective immunity was calculated as one minus the risk ratio multiplied by 100. 2 456 791 individuals were included in the study, contributing 53·1 million person-days of observation for the SARS-CoV-2-naive group, 3·4 million person-days for the pre-omicron group, 6·6 million person-days for the BA.1 group, and 13·7 million person-days for the BA.2 group between Oct 1, 2022, and Nov 1, 2022. Compared with SARS-CoV-2-naive individuals, first infections with pre-omicron variants did not confer protection against reinfection with BA.4 or BA.5 (IRR 0·87 [95% CI 0·73-1·05] for pre-omicron infection with booster vaccination) or XBB (IRR 1·29 [1·23-1·35] for pre-omicron infection with booster vaccination). Previous BA.2 infection with booster provided the greatest protection against reinfection, but this was lower against reinfection with XBB (protective immunity 51%; 95% CI 49-53) than against reinfection with BA.4 or BA.5 (78%; 74-82). Protection conferred by previous BA.2 infection against XBB reinfection waned faster over time from first infection (from 74% [72-75] at 3-6 months to 49% [47-52] at 7-8 months) than protection against BA.4 or BA.5 reinfection (from 87% [82-90] at 3-6 months to 74% [66-80] at 7-8 months). Protection against XBB reinfection conferred by a previous omicron infection with vaccination was lower and waned faster than protection against BA.4 or BA.5 reinfection, which is indicative of the greater immune evasiveness of the XBB sublineage. Although severe COVID-19 is uncommon, populations remain vulnerable to future reinfection waves from emerging SARS-CoV-2 variants despite high rates of vaccination and infection, as reflected by substantially higher reinfection rates during Singapore's XBB wave than during the previous BA.5-driven wave. Policy makers could consider emerging public health interventions, such as omicron-adapted bivalent vaccines, to maintain population immunity against COVID-19. None.

A bifurcation analysis and model of Covid-19 transmission dynamics with post-vaccination infection impact

SARS COV-2 (Covid-19) has imposed a monumental socio-economic burden worldwide, and its impact still lingers. We propose a deterministic model to describe the transmission dynamics of Covid-19, emphasizing the effects of vaccination on the prevailing epidemic. The proposed model incorporates current information on Covid-19, such as reinfection, waning of immunity derived from the vaccine, and infectiousness of the pre-symptomatic individuals into the disease dynamics. Moreover, the model analysis reveals that it exhibits the phenomenon of backward bifurcation, thus suggesting that driving the model reproduction number below unity may not suffice to drive the epidemic toward extinction. The model is fitted to real-life data to estimate values for some of the unknown parameters. In addition, the model epidemic threshold and equilibria are determined while the criteria for the stability of each equilibrium solution are established using the Metzler approach. A sensitivity analysis of the model is performed based on the Latin Hypercube Sampling (LHS) and Partial Rank Correlation Coefficients (PRCCs) approaches to illustrate the impact of the various model parameters and explore the dependency of control reproduction number on its constituents parameters, which invariably gives insight on what needs to be done to contain the pandemic effectively. The foregoing notwithstanding, the contour plots of the control reproduction number concerning some of the salient parameters indicate that increasing vaccination coverage and decreasing vaccine waning rate would remarkably reduce the value of the reproduction number below unity, thus facilitating the possible elimination of the disease from the population. Finally, the model is solved numerically and simulated for different scenarios of disease outbreaks with the findings discussed.

An Age of Infection Kernel, an R Formula, and Further Results for Arino–Brauer A, B Matrix Epidemic Models with Varying Populations, Waning Immunity, and Disease and Vaccination Fatalities

In this work, we first introduce a class of deterministic epidemic models with varying populations inspired by Arino et al. (2007), the parameterization of two matrices, demography, the waning of immunity, and vaccination parameters. Similar models have been focused on by Julien Arino, Fred Brauer, Odo Diekmann, and their coauthors, but mostly in the case of “closed populations” (models with varying populations have been studied in the past only in particular cases, due to the difficulty of this endeavor). Our Arino–Brauer models contain SIR–PH models of Riano (2020), which are characterized by the phase-type distribution (α→,A), modeling transitions in “disease/infectious compartments”. The A matrix is simply the Metzler/sub-generator matrix intervening in the linear system obtained by making all new infectious terms 0. The simplest way to define the probability row vector α→ is to restrict it to the case where there is only one susceptible class s, and when matrix B (given by the part of the new infection matrix, with respect to s) is of rank one, with B=bα→. For this case, the first result we obtained was an explicit formula (12) for the replacement number (not surprisingly, accounting for varying demography, waning immunity and vaccinations led to several nontrivial modifications of the Arino et al. (2007) formula). The analysis of (A,B) Arino–Brauer models is very challenging. As obtaining further general results seems very hard, we propose studying them at three levels: (A) the exact model, where only a few results are available—see Proposition 2; and (B) a “first approximation” (FA) of our model, which is related to the usually closed population model often studied in the literature. Notably, for this approximation, an associated renewal function is obtained in (7); this is related to the previous works of Breda, Diekmann, Graaf, Pugliese, Vermiglio, Champredon, Dushoff, and Earn. (C) Finally, we propose studying a second heuristic “intermediate approximation” (IA). Perhaps our main contribution is to draw attention to the importance of (A,B) Arino–Brauer models and that the FA approximation is not the only way to tackle them. As for the practical importance of our results, this is evident, once we observe that the (A,B) Arino–Brauer models include a large number of epidemic models (COVID, ILI, influenza, illnesses, etc.).

Clinical features and severe outcome predictors of COVID-19 vaccine breakthrough infection among hospitalized patients: results from Egypt severe acute respiratory infections sentinel surveillance, 2021–2022

BackgroundCOVID-19 vaccines are effective against infections and outcomes; however, breakthrough infections (VBT) are increasingly reported, possibly due to waning of vaccine-induced immunity or emerging variants. Most studies have focused on determining VBT rate based on antibody levels. This study aims at describing clinical features, risks, time trends, and outcomes of COVID-19 VBT among hospitalized patients in Egypt.MethodsData of SARS-CoV-2 confirmed patients hospitalized in 16 hospitals was obtained from the severe acute respiratory infections surveillance database, September 2021-April 2022. Data includes patients’ demographics, clinical picture, and outcomes. Descriptive analysis was performed and patients with VBT were compared to not fully vaccinated (UPV). Bivariate and multivariate analyses were performed using Epi Info7 with a significance level < 0.05 to identify VBT risk factors.ResultsOverall, 1,297 patients enrolled, their mean age 56.7 ± 17.0 years, 41.5% were males, 64.7% received inactivated, 25.% viral vector, and 7.7% mRNA vaccine. VBT was identified in 156(12.0%) patients with an increasing trend over time. VBT significantly was higher in (16–35 years) age, males, in those who received inactivated vaccine compared to corresponding groups of UPV (14.1 vs. 9.0%, p < 0.05 and 57.1 vs. 39.4%, p < 0.001 and 64.7 vs. 45.1, p < 0.01 respectively). Whereas receiving mRNA vaccine was significantly protective against VBT (7.7 vs. 21.6%, p < 001). VBT patients tend to have shorter hospital stays and lower case fatality (mean hospital days = 6.6 ± 5.5 vs. 7.9 ± 5.9, p < 0.01 and CFR = 28.2 vs. 33.1, p < 0.01 respectively). MVA identified younger ages, male gender, and inactivated vaccines as risks for VBT.ConclusionThe study indicated that COVID-19 vaccines significantly reduce hospital days and fatality. VBT trend is on the rise and males, young ages, and inactivated vaccine receivers are at higher risk. Caution regarding relaxation of personal preventive measures in areas with higher or increasing incidences of COVID-19, particularly for the at-risk group even if they are vaccinated. The vaccination strategy should be revised to reduce VBT rate and increase vaccine effectiveness.

Review and future perspectives on the integration characteristics for equine lentivirus in the host genome.

Despite over 40 years of research on the human immunodeficiency virus type 1 (HIV-1) vaccine, we still lack a considerable progress. Equine infectious anemia virus (EIAV) is a lentivirus in the Retroviridae family, akin to HIV-1 in genome structure and antigenicity. EIA is an important infectious disease in equids, characterized by anemia, persistent infection, and repeated fevers. The EIAV attenuated vaccine in China is the only lentiviral vaccine used on a large scale. Elucidating the mechanism of waning and induction of protective immunity from this attenuated vaccine strain will provide a critical theoretical basis and reference point for vaccine research, particularly in the development of lentivirus vaccines, with far-reaching scientific value and social significance. In this paper, we summarize the information related to EIAV integration site selection, particularly for the Chinese EIAV attenuated vaccine strains on the equine genome. This may improve our mechanistic understanding of EIAV virulence reduction at the host genome level. The obtained data may help elucidate the biological characteristics of EIAV, particularly the Chinese attenuated EIAV vaccine strain, and provide valuable information regarding retroviral infections, particularly lentiviral infection and associated therapeutic vectors.

A mathematical model for COVID-19 considering waning immunity, vaccination and control measures

In this work we define a modified SEIR model that accounts for the spread of infection during the latent period, infections from asymptomatic or pauci-symptomatic infected individuals, potential loss of acquired immunity, people’s increasing awareness of social distancing and the use of vaccination as well as non-pharmaceutical interventions like social confinement. We estimate model parameters in three different scenarios—in Italy, where there is a growing number of cases and re-emergence of the epidemic, in India, where there are significant number of cases post confinement period and in Victoria, Australia where a re-emergence has been controlled with severe social confinement program. Our result shows the benefit of long term confinement of 50% or above population and extensive testing. With respect to loss of acquired immunity, our model suggests higher impact for Italy. We also show that a reasonably effective vaccine with mass vaccination program are successful measures in significantly controlling the size of infected population. We show that for a country like India, a reduction in contact rate by 50% compared to a reduction of 10% reduces death from 0.0268 to 0.0141% of population. Similarly, for a country like Italy we show that reducing contact rate by half can reduce a potential peak infection of 15% population to less than 1.5% of population, and potential deaths from 0.48 to 0.04%. With respect to vaccination, we show that even a 75% efficient vaccine administered to 50% population can reduce the peak number of infected population by nearly 50% in Italy. Similarly, for India, a 0.056% of population would die without vaccination, while 93.75% efficient vaccine given to 30% population would bring this down to 0.036% of population, and 93.75% efficient vaccine given to 70% population would bring this down to 0.034%.

Design of a stabilized RBD enables potently neutralizing SARS-CoV-2 single-component nanoparticle vaccines

Waning immunity and emerging variants necessitate continued vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Improvements in vaccine safety, tolerability, and ease of manufacturing would benefit these efforts. Here, we develop a potent and easily manufactured nanoparticle vaccine displaying the spike receptor-binding domain (RBD). Computational design to stabilize the RBD, eliminate glycosylation, and focus the immune response to neutralizing epitopes results in an RBD immunogen that resolves issues hindering the efficient nanoparticle display of the native RBD. This non-glycosylated RBD can be genetically fused to diverse single-component nanoparticle platforms, maximizing manufacturing ease and flexibility. All engineered RBD nanoparticles elicit potently neutralizing antibodies in mice that far exceed monomeric RBDs. A 60-copy particle (noNAG-RBD-E2p) also elicits potently neutralizing antibodies in non-human primates. The neutralizing antibody titers elicited by noNAG-RBD-E2p are comparable to a benchmark stabilized spike antigen and reach levels against Omicron BA.5 that suggest that it would provide protection against emerging variants.

Cost effectiveness of fractional doses of COVID-19 vaccine boosters in India.

Coronavirus disease 2019 (COVID-19) continues to be a major global public health crisis that exacts significant human and economic costs. Booster vaccination of individuals can improve waning immunity and reduce the impact of community epidemics. Using an epidemiological model that incorporates population-level severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and waning of vaccine-derived immunity, we identify the hypothetical potential of mass vaccination with fractionated vaccine doses specific to ChAdOx1 nCoV-19 (AZD1222 [Covishield]; AstraZeneca) as an optimal and cost-effective strategy in India's Omicron outbreak. We find that the optimal strategy is 1/8 fractional dosing under mild (Re ∼ 1.2) and rapid (Re ∼ 5) transmission scenarios, leading to an estimated $6 (95% confidence interval [CI]: -13, 26) billion and $2 (95% CI: -26, 30) billion in health-related net monetary benefit over 200days, respectively. Rapid and broad use of fractional dosing for boosters, together with delivery costs divided by fractionation, could substantially gain more net monetary benefit by $11 (95% CI: -10, 33) and $2 (95% CI: -23, 28) billion, respectively, under the mild and rapid transmission scenarios. Mass vaccination with fractional doses of COVID-19 vaccines to boost immunity in a vaccinated population could be a cost-effective strategy for mitigating the public health costs of resurgences caused by vaccine-evasive variants, and fractional dosing deserves further clinical and regulatory evaluation. Financial support was provided by the AIR@InnoHK Program from Innovation and Technology Commission of the Government of the Hong Kong Special Administrative Region.

Immunisation against COVID-19 in Pregnancy and of Women Planning Pregnancy

Following reports of the first human SARS-CoV2 infection in December 2019 from Wuhan Province, China, there was such rapid spread that by March 2021, the World Health Organization (WHO) had declared a pandemic. Over 6.5 million people have died from this infection worldwide, although this is most likely an underestimate. Until vaccines became available, mortality and severe morbidity were costly in terms of life lost as well as the cost of supporting the severely and acutely ill. Vaccination changed the landscape, and following worldwide adoption, life has gradually been returning to normal. The speed of production of the vaccines was unprecedented and undoubtedly ushered in a new era in the science of fighting infections. The developed vaccines were on the already known platforms for vaccine delivery: inactivated virus, virus vector, virus-like particles (VLP) subunit, DNA and mRNA. The mRNA platform was used for the first time to deliver vaccines to humans. An understanding of these platforms and the pros and cons of each are important for clinicians who are often challenged by the recipients on the advantages and risks of these vaccines. These vaccines have so far and reassuringly been shown to be safe in reproduction (with no effect on gametes) and pregnancy (not associated with congenital malformations). However, safety remains paramount and continuing vigilance is critical, especially against rare fatal complications such as vaccine-induced thrombocytopenia and myocarditis. Finally, the waning immunity months after vaccination means repeated immunisation is likely to be ongoing, but just how often and how many such revaccinations should be recommended remains uncertain. Research into other vaccines and alternate delivery methods should continue as this infection is likely to be around for a long time.