Vaccine Regimen Research Articles

Antibody response to different COVID-19 vaccine regimes: a review

COVID-19 pandemic initiated a race for the development of vaccines. Different technologies have been used to produce them, including inactivated whole-virus, nucleic acid, and adenovirus vector platforms. COVID-19 vaccination was initiated with two doses called “primary vaccination” which can be homologous (the same vaccine used in the first and second dose) or heterologous (different vaccines used in the first and second dose). Waning of vaccine-induced antibodies over time combined with the emerging SARS-CoV-2 variants of concern (VOCs) suggested the importance and necessity of a “booster shot” of the vaccine. The additional dose can be done with the same vaccine used in the primary vaccination (homologous booster) or vaccines can be mix-and-match (heterologous booster). Immune escape of VOCs raises the question of which is the best combination of COVID-19 vaccines. Therefore, this review summarizes the main findings of humoral response to different SARS-CoV-2 vaccination regimens.

Transplantable Murine Tumors in the Studies of Peptide Antitumor Vaccines.

Numerous studies have shown that antitumor vaccines based on synthetic peptides are safe and can induce both CD8+ and CD4+ tumor-specific T cell responses. However, clinical results are still scarce, and such approach to antitumor treatment has not gained a wide implication, yet. Recently, particular advances have been achieved due to tumor sequencing and the search for immunogenic neoantigens caused by mutations. One of the most important issues for peptide vaccines, along with the choice of optimal adjuvants and vaccination regimens, is the search for effective target antigens. Extensive studies of peptide vaccines, including those on murine models, are required to reveal the effective vaccine constructs. The review presents transplantable murine tumors with the detected peptides that showed antitumor efficacy as a vaccine compound.

Comparison of the Efficacy of Different Schemes for Using Recombinant Vector Vaccines against Ebola Fever, Based on Vaccinia Virus, MVA Strain

The aim of this review was to investigate the use of the vaccines based on vaccinia virus, MVA stain, and adenovirus vectors for the prevention of Ebola virus disease. The recombinant MVA strains expressing antigen determinants of Filoviridae family representatives were assessed as possible candidates for vaccine preparations. Application of this virus as a vaccine vector is conditioned by the absence of herd immunity to smallpox and its safety for healthy adult volunteers, children, adolescents, individuals suffering from tuberculosis, persons aged 56–80 years, people with diagnosed atopic dermatitis, AIDS. Furthermore, immunization with the vaccine on the basis of vaccinia virus, MVA strain, does not cause complications associated with cardiovascular diseases. Preclinical trials on immunogenicity and protective efficiency were carried out on immune-competent and immune-compromised mice; guinea pigs adapted to Ebola virus; rhesus macaques and cynomolgus monkeys. Presented are the results of experiments on the creation of vaccines expressing either only viral glycoprotein or viral glycoprotein and structural protein Vp40. Given that Ebola fever and other filovirus infection outbreaks are hard to predict, multivalent vaccines that would be able to provide protection against all filovirus species were designed. Clinical trials on simultaneous use of the vaccines based on recombinant adenovirus vectors and MVA strain showed more pronounced safety of vaccines on the basis of recombinant MVA strain. Studies of humoral and T-cell immune responses have revealed that this vector is more suitable for booster vaccination in case of heterologous prime/booster immunization scheme. Vaccination regimens for forming strong durable immune responses have been analyzed. Epidemiological modeling provided evidence that preventive immunization leading to long-term immunity in healthy population in areas of high epidemic risk will be of greater benefit in terms of controlling future outbreaks compared to ring immunization that was effective during smallpox eradication campaign. Increased immunity level, induced by prime/booster vaccination, persisting for a long period of time, will have an advantage over accelerated ring immunization; when the duration of protection is more significant than the speed it is formed at.

Absolute quantitation of binding antibodies from clinical samples

The quantitation of antibody responses is a critical requirement for the successful development of vaccines and therapeutics that often relies on the use of standardized reference materials to determine relative quantities within biological samples. The validity of comparing responses across assays using arbitrarily defined reference values is therefore limited. We developed a generalizable method known as MASCALE (Mass Spectrometry Enabled Conversion to Absolute Levels of ELISA Antibodies) for absolute quantitation of antibodies by calibrating ELISA reference sera using mass spectrometry. Levels of proteotypic peptides served as a proxy for human IgG, allowing the conversion of responses from arbitrary values to absolute amounts. Applications include comparison of binding assays at two separate laboratories and evaluation of cross-clade magnitude-breadth responses induced by an investigational HIV-1 vaccine regimen. MASCALE addresses current challenges in the interpretation of immune responses in clinical trials and expands current options available to make suitable comparisons across different settings.

Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Subvariant Neutralization Following a Primary Vaccine Series of NVX-CoV2373 and BNT162b2 Monovalent Booster Vaccine.

We evaluated the immunologic response to a novel vaccine regimen that included 2 doses of NVX-CoV2373 (Novavax) followed by 1 dose of BNT162b2 (Pfizer-BioNTech) monovalent booster vaccine. A durable neutralizing antibody response to Omicron BA.4/BA.5 and BA.1 variants was observed at month 6 after the booster, while immune escape was noted for the XBB.1.5 variant.

Chitosan-Deficient Cryptococcus as Whole-Cell Vaccines.

Creating a safe and effective vaccine against infection by the fungal pathogen Cryptococcus neoformans is an appealing option that complements the discovery of new small molecule antifungals. Recent animal studies have yielded promising results for a variety of vaccines that include live-attenuated and heat-killed whole-cell vaccines, as well as subunit vaccines formulated around recombinant proteins. Some of the recombinantly engineered cryptococcal mutants in the chitosan biosynthesis pathway are avirulent and very effective at conferring protective immunity. Mice vaccinated with these avirulent chitosan-deficient strains are protected from a lethal pulmonary infection with C. neoformans strain KN99. Heat-killed derivatives of the vaccination strains are likewise effective in a murine model of infection. The efficacy of these whole-cell vaccines, however, is dependent on a number of factors, including the inoculation dose, route of vaccination, frequency of vaccination, and the specific mouse strain used in the study. Here, we present detailed methods for identifying and optimizing various factors influencing vaccine potency and efficacy in various inbred mouse strains using a chitosan-deficient cda1Δcda2Δcda3Δ strain as a whole-cell vaccine candidate. This chapter describes the protocols for immunizing three different laboratory mouse strains with vaccination regimens that use intranasal, orotracheal, and subcutaneous vaccination routes after the animals were sedated using two different types of anesthesia.

Lymph node and tumor-associated PD-L1+ macrophages antagonize dendritic cell vaccines by suppressing CD8+ T cells

Current immunotherapies provide limited benefits against Tcell-depleted tumors, calling for therapeutic innovation. Using multi-omics integration of cancer patient data, we predict a type I interferon (IFN) responseHIGH state of dendritic cell (DC) vaccines, with efficacious clinical impact. However, preclinical DC vaccines recapitulating this state by combining immunogenic cancer cell death with induction of type I IFN responses fail to regress mouse tumors lacking Tcell infiltrates. Here, in lymph nodes (LNs), instead of activating CD4+/CD8+ Tcells, DCs stimulate immunosuppressive programmed death-ligand 1-positive (PD-L1+) LN-associated macrophages (LAMs). Moreover, DC vaccines also stimulate PD-L1+ tumor-associated macrophages (TAMs). This creates two anatomically distinct niches of PD-L1+ macrophages that suppress CD8+ Tcells. Accordingly, a combination of PD-L1 blockade with DC vaccines achieves significant tumor regression by depleting PD-L1+ macrophages, suppressing myeloid inflammation, and de-inhibiting effector/stem-like memory Tcells. Importantly, clinical DC vaccines also potentiate Tcell-suppressive PD-L1+ TAMs in glioblastoma patients. We propose that a multimodal immunotherapy and vaccination regimen is mandatory to overcome Tcell-depleted tumors.

The efficacy of simultaneous successive classic and variant infectious bronchitis virus vaccines versus circulating variant II Egyptian field virus.

Being a ubiquitous, highly contagious virus with a continuous mutation and a large number of evolutions worldwide, the infectious bronchitis virus (IBV) continues to wreak problems among Egyptian chickens and generate economic losses. The commonly applied IBV vaccination protocols in broilers include alternatives to classic and/or variant attenuated live virus vaccines. The current study targeted to assess the protective efficacy of concurrent and successive Ma5 and 4/91 vaccine strain regimens against the field variant II IBV strain (IBV-EGY-ZU/Ck-127/2021) in chickens. Commercial broiler chickens were vaccinated with Ma5 and 4/91 strains simultaneously at 1 and 14 days of age. The evaluation parameters included clinical protection and humoral and early innate immunity aspects in the renal tissues of vaccinated and infected birds. The vaccine regimen ameliorated the clinical and histopathological lesions against variant II IBV and enhanced body gain as well as succeeded in preventing tracheal shedding and minimizing cloacal shedding of the field virus. The IL-1β mRNA gene expression was evident as early as 24 hours, with highly significant upregulation at 48 hours post vaccination and 24 hours post challenge (PC) in vaccinated birds. Remarkable upregulation was observed in oligoadenylate synthetases (OAS) expression 48 hours PC in vaccinated and unvaccinated infected birds. The vaccinated birds developed a significant antibody titer of 704.0 ± 111.98 at 28 days of age, with a consistent antibody titer increase after the challenge. Overall, a combination of heterologous protectotype commercial vaccines achieved good protection against the Egyptian variant II IBV strain. This vaccine program could be an effective protocol against the threat posed by IBV viruses circulating in the Egyptian field.

Immunogenicity and real-world effectiveness of COVID-19 vaccines in Lebanon: Insights from primary and booster schemes, variants, infections, and hospitalization.

In this study, we conducted a case-control investigation to assess the immunogenicity and effectiveness of primary and first booster homologous and heterologous COVID-19 vaccination regimens against infection and hospitalization, targeting variants circulating in Lebanon during 2021-2022. The study population comprised active Lebanese military personnel between February 2021 and September 2022. Vaccine effectiveness (VE) against laboratory-confirmed SARS-CoV-2 infection and associated hospitalization was retrospectively determined during different variant-predominant periods using a case-control study design. Vaccines developed by Sinopharm, Pfizer, and AstraZeneca as well as Sputnik V were analyzed. Prospective assessment of humoral immune response, which was measured based on the SARS-CoV-2 antispike receptor binding domain IgG titer, was performed post vaccination at various time points, focusing on Sinopharm and Pfizer vaccines. Statistical analyses were performed using IBM SPSS and GraphPad Prism. COVID-19 VE remained consistently high before the emergence of the Omicron variant, with lower estimates during the Delta wave than those during the Alpha wave for primary vaccination schemes. However, vaccines continued to offer significant protection against infection. VE estimates consistently decreased for the Omicron variant across post-vaccination timeframes and schemes. VE against hospitalization declined over time and was influenced by the variant. No breakthrough infections progressed to critical or fatal COVID-19. Immunogenicity analysis revealed that the homologous Pfizer regimen elicited a stronger humoral response than Sinopharm, while a heterologous Sinopharm/Pfizer regimen yielded comparable results to the Pfizer regimen. Over time, both Sinopharm's and Pfizer's primary vaccination schemes exhibited decreased humoral immunity titers, with Pfizer being a more effective booster than Sinopharm. This study, focusing on healthy young adults, provides insights into VE during different pandemic waves. Continuous research and monitoring are essential for understanding vaccine-mediated immune responses under evolving circumstances.

Immunogenicity and Safety of the Three-Dose COVID-19 Vaccine Regimen in Patients Receiving Renal Replacement Therapy: A Systematic Review and Meta-Analysis

Background: A three-dose regimen is the current standard for COVID-19 vaccination, but systematic data on immunogenicity and safety in chronic kidney disease patients remains limited. Objectives: We conducted a meta-analysis on the immunogenicity and safety of three-dose COVID-19 vaccination in patients on renal replacement therapy (RRT). Methods: Systematic literature search in four electronic databases yielded twenty eligible studies (2,117 patients, 94% of whom received mRNA vaccines) for meta-analysis. Results: The overall seropositivity rate of anti-SARS-CoV-2 was 74.2% (95% CI: 65.0–83.4%) after three-dose COVID-19 vaccination. The seropositivity rate of anti-SARS-CoV-2 in kidney transplant recipients (KTRs) was 64.6% (95% CI: 58.7–70.5%), and 43.5% (95% CI: 38.5–48.6%) of non-responders after second dose became seropositive after third dose. The seropositivity rate of anti-SARS-CoV-2 was 92.9% (95% CI: 89.5–96.2%) in dialysis patients, and 64.6% (95% CI: 46.8–82.3%) of non-responders after second dose became seropositive after third dose. In KTRs, each year increase in transplant vintage was associated with 35.6% increase in anti-SARS-CoV-2 seropositivity (95% CI: 15.9–55.4%, p = 0.01). There were no serious adverse events attributed to vaccination in KTRs, and the commonest local and systemic adverse events were injection site pain and fatigue, respectively. Conclusion: Three-dose COVID-19 vaccination regimen in patients on RRT is associated with reduced immunogenicity, especially in KTRs. There are no adverse events associated with third-dose COVID-19 vaccine in KTRs.

Determination of COVID-19 Late Disorders as Possible Long-COVID and/or Vaccination Consequences.

In this era in which the vast majority of the global population have developed COVID-19 infection and/or got vaccinated against it, identification of the late disorders as the vaccines' side effect or long-COVID manifestation seems essential. This study included the vaccinated individuals of 4 different vaccine regimens including inactivated virus-based, subunit protein, and adenovirus-based vaccines in a follow-up schedule 6-month post the booster shot. All the documented vaccine adverse events were thoroughly assessed considering the cases' medical history by Adverse Events Committee of Pasteur Institute of Iran. Totally 329 individuals who got 3 doses of vaccination were followed 6 months after the booster shots among whom 41 (12.4%) cases with the mean age of 40.9 ± 10.48 years had a type of disorder. Gynecological and osteoarticular involvements were the most common recorded disorders of which 73.1% were possibly linked to vaccination outcomes and the rest were affected by both long-COVID-19 and vaccination. Notably, the average time of symptoms persistence was 155 ± 10.4 days. This study has the advantage of long-term follow-up which presents various forms of late events in each episode of COVID-19 infection and vaccination. About 26.8% of people with persistent complications suffered from both long-COVOD/ vaccination in whom the differentiation between the vaccine side effect and long-COVID manifestation was quite challenging. Long-term follow-up studies in large population seems essential to outline the role of long-COVID and vaccination regarding persistent complications.

Single ChAdOx1 nCoV-19 dose elicits stronger immune response in previously infected individuals than in SARS-CoV2 naive persons.

Current vaccines against COVID-19 effectively reduce morbidity and mortality and are vitally important for controlling the pandemic. Between December 2020 and February 2021, adenoviral vector vaccines such as ChAdOx1 (AstraZeneca-Oxford) were put in use. Recent reports demonstrate robust serological responses to a single dose of messenger RNA vaccines in individuals previously infected with SARS-CoV-2. We aimed to study the association between previous COVID-19 infection and antibody levels after a single dose of ChAdOx1 nCoV-19. This cross-sectional study was conducted on 657 individuals who were either convalescent or SARS-CoV-2 naive and had received one dose of ChAdOx1 (AstraZeneca). A questionnaire was used to collect data on age, sex, and self-reported history of COVID-19 infection. We then compared the average levels of immunoglobulin G (IgG) between the previously infected and COVID-19-naive participants. We compared the antibody responses of individuals with confirmed prior COVID-19 infection with those of individuals without prior evidence of infection. The mean antibody levels in those who reported no history of COVID-19 infection were substantially lower than in those who were previously infected, in both males and females. Sex-related differences were observed when we compared antibody levels between men and women. In males, anti-S IgG antibody levels were higher in those who had been previously infected (156.1 vs. 87.69 AU/mL, p = .009), compared with the same pattern was observed in females (113.5 vs. 90.69 AU/mL, p = .005). Previous COVID-19 infection is associated with higher levels of SARS-CoV-2 antibodies following ChAdOx1 (AstraZeneca) vaccination. Our finding supports the notion that a single dose of ChAdOx1 nCoV-19 administered post-SARS-CoV-2 infection serves as an effective immune booster. This provides a possible rationale for a single-dose vaccine regimen for previously infected individuals.

Cost-effectiveness analysis of single-dose or 2-dose of bivalent, quadrivalent, or nonavalent HPV vaccine in a low/middle-income country setting.

To compare the health impact and economic benefits among individuals who did not receive the human papillomavirus (HPV) vaccine to those who received a single dose, or 2 doses. The comparison was stratified by 4 types of vaccine in conjunction with primary HPV screening in a low/middle-income country setting. A Markov model was employed to simulate HPV infection and cervical cancer in a cohort of 100,000 12-year-old girls free of HPV. The study scrutinized 9 strategies: 1 dose and 2 doses of 2vHPV (Cervarix®), 2vHPV (Cecolin®), 4vHPV (Gardasil®), 9vHPV vaccine (Gardasil9®), and no vaccination. The primary outcome measure was the quality-adjusted life year (QALY) of each strategy. Incremental cost-effectiveness ratios were estimated over a lifetime horizon, accompanied by sensitivity analyses conducted. All vaccination programs yielded 41,298-71,057 QALYs gained accompanied by cost savings of 14,914,186-19,821,655 USD compared to no vaccination. Administering 2 doses of 9vHPV vaccine emerged as the most cost-effective strategy, boasting 406 USD/QALY, within a lower willingness to pay threshold. Sensitivity analysis demonstrated an 80% probability of the cost-effectiveness of the 2 doses of 9vHPV vaccine regimen. Furthermore, uncertainty around the costs of vaccination and vaccine efficacy exerted the most substantial influence on the cost-effectiveness findings. Oping for 2 doses of 9vHPV vaccine in conjunction with a primary HPV screening represents the most cost-effective option for implementing a school-based HPV vaccination program targeting 12-year-old girls in Thailand. Such findings provide valuable insights for policymakers in the realm of cervical cancer prevention.

COVID-19 Vaccine Policy Implementation and Differential Vaccine Uptake Trajectories in Chicago Communities.

Since the onset of the COVID-19 pandemic, multiple public health interventions have been implemented to respond to the rapidly evolving pandemic and community needs. This article describes the scope, timing, and impact of coordinated strategies for COVID-19 vaccine uptake in Chicago for the first year of vaccine distribution. Using a series of interviews with public health officials and leaders of community-based organizations (CBOs) who participated in the implementation of the citywide COVID-19 vaccine outreach initiatives, we constructed a timeline of vaccine outreach initiatives. The timeline was matched to the vaccine uptake rates to explore the impact of the vaccine outreach initiatives by community area. Finally, we discussed the nature of policy initiatives and the level of vaccine uptake in relation to community characteristics. The Chicago Department of Public Health (CDPH) implemented myriad vaccine outreach strategies, including mass vaccination sites, improved access, and community-level vaccine campaigns. Protect Chicago+ was the primary vaccine outreach effort initiated by the CDPH, which identified 15 highly vulnerable community areas. More than 2.7 million (67%) Chicagoans completed the vaccine regimen by December 2021. Black (51.3%) Chicagoans were considerably less likely to be vaccinated than Asian (77.6%), White (69.8%), and Hispanic (63.6%) Chicago residents. In addition, there were significant spatial differences in the rate of COVID-19 vaccine completion: predominantly White and Hispanic communities, compared with Black communities, had higher rates of vaccine completion. The community outreach efforts to improve COVID-19 vaccine uptake in Chicago have shown the importance of community-engaged approaches in pandemic responses. Despite citywide efforts to build community infrastructure, Black communities had relatively lower levels of vaccine uptake than other communities. Broader social restructuring to mitigate disinvestment and residential segregation and to ameliorate medical mistrust will be needed to prepare for future pandemics and disasters.

Monitoring and evaluation of provincial classical swine fever immunization implementation with an E2 subunit vaccine in Jeju Island, South Korea.

Accidental vaccination with a live attenuated low-virulence strain of Miyagi (LOM) vaccine led to the reemergence of classical swine fever virus (CSFV) in Jeju province, South Korea in 2014. To control the continual outbreaks of LOM-derived CSFV, the provincial government launched a provincial mass vaccination project using a CSF-E2 subunit vaccine. We conducted this study to assess the herd immunity level and outcomes of E2 vaccine-based immunization in breeding and growing herds on Jeju Island during 2020-2021. A large-scale vaccination trial using the Bayovac CSF-E2 vaccine investigated its efficacy in breeding and growing herds under farm application conditions (10 CSFV-affected and three CSFV-naïve swine farms). The level of herd immunity in each farm was classified into three (S1-S3) and six (G1-G6) profiles in breeding and growing herds, respectively. Immunity monitoring revealed a remarkable improvement in the herd immunity status in all farms. The majority (10/13) of farms, including CSFV-free farms, showed the S1G1 immunity profile in 2021, indicating the appropriate implementation of the advised vaccination regime. Moreover, there were significant decreases in Erns seropositivity from 100% to 50% and 25.9% to 4.3% at farm and pig levels, respectively. In particular, all farms were confirmed as CSFV free in the growing-finishing herds. Our large-scale trial demonstrated the effectiveness of the E2 subunit vaccine in establishing herd immunity stabilization and eliminating CSFV circulation in the affected farms and highlighted the need for a provincial vaccination policy to regain the CSF-free status on Jeju Island.

Application of Memory Natural Killer Cells in HIV Vaccine

Human immunodeficiency virus (HIV) is a formidable infection targeting the intricate defense mechanisms of the human body, primarily focusing its assault on the vital white blood cells known as CD4 cells. HIV impairs these CD4 cells, reducing resistance to opportunistic infections. In 2022, 630,000 people died from HIV-related causes globally due to the lack of preventative vaccines and effective treatment. The pursuit of an effective HIV vaccine remains a critical endeavor in global health, necessitating innovative strategies that can elicit robust and durable immune responses. Natural killer (NK) cells, renowned for their swift and inherent cytotoxic prowess, constitute a critical element of innate immunity, typically thought to be deficient in memory abilities. Fascinatingly, NK cells have now become the focal point of scientific research due to emerging evidence suggesting the presence of memory-like characteristics within their functional repertoire. Through a comprehensive exploration of NK cell subpopulations and the strategic application of cytokines or other stimuli to induce the development of memory-generating NK cell subpopulations, the potential for enhancing the efficacy of HIV vaccines emerges. This approach holds promise in bolstering the creation of adaptive immunity and advancing the quest for effective HIV immunization strategies. The study offers valuable insights into the potential of NK memory cells as a viable component of future HIV vaccine regimens, suggesting avenues for further research and development in the quest to mitigate the global burden of HIV.

Review on the Economic Impacts of Lumpy Skin Disease of Cattle and Its Prevention and Control Strategies in Ethiopia

Lumpy skin disease (LSD) is an infectious disease of cattle, caused by a Lumpy Skin Disease Virus. It is an economically important viral disease of cattle affecting all ages and breeds that can be prevented by vaccination in endemic regions including Ethiopia. LSD is an OIE listed disease because of considerable financial losses and in Ethiopia due to the endemic nature of LSD; the country is facing serious difficulties in exporting live cattle and their products. In addition, this situation contributes a negative impact on the national economic growth through the loss of meat and milk production and poor quality of skin and hides. Serious economic losses can follow outbreaks that have a high morbidity and high mortality rates of 40 percent or more have been encountered. There is no specific antiviral treatment available for LSD-infected cattle. The disease is now the problem of almost all the regions and agro ecological zones of Ethiopia. Major outbreaks of LSD have been occurred in different regions of Ethiopia. Two vaccines, however, Neethling and Kenya sheep and goat pox virus, have been used widely in Africa with success. Preventing movement the diseased animals along with vector control, regular annual vaccinations and awareness creation for cattle owners play great role in disease prevention and control. The disease outbreak was observed in the cattle regardless of previous vaccination with Kenyan sheep- and goat pox vaccine the occurrence of LSD outbreak scale, despite the use of a vaccination regime, is suggestive of vaccine failure. Apparent emerging vaccine failure is a serious problem for efficient control of LSD, as the disease has been manifested by high morbidity and mortality rates, regardless of vaccination status. Consequently continuous surveillance on the status of the disease and genetic information on circulating field viruses is mandatory in order to take effective measures for the control of the disease in the country.

Long-Term SARS-CoV-2-Specific Humoral and T Cell Responses after the BNT162b2 or BBIBP-CorV Booster and the Incidence of Breakthrough Infections among Healthcare Workers.

The effectiveness of COVID-19 vaccines developed against the original virus strain deteriorated noticeably in efficacy against the Omicron variant (B.1.1.529). Moreover, the immunity developed after vaccination or due to natural infection rapidly waned. In the present study, covering this period, we summarize the incidence of breakthrough infections among healthcare workers (HCWs) with respect to administration of the three vaccine doses. Additionally, we evaluate the long-term SARS-CoV-2-specific humoral and T cell responses at two different time points: six and twelve months after receipt of the third (booster) dose. The spike-protein-specific antibody levels and the quantity of structural-protein-specific T cells were evaluated at these time points and compared with the values measured earlier, 14 days after the booster vaccination. The study participants were categorized into two cohorts: Members of the first cohort received a two-dose BNT162b2 mRNA-based vaccine regimen, followed by an additional BNT162b2 booster six months later. Individuals in the second cohort received an inactivated-virus-based BBIBP-CorV booster six months after the initial two-dose BNT162b2 vaccination. Overall, 64.3% of participants were infected with SARS-CoV-2 confirmed by PCR or antigen test; however, additional subjects from the first cohort (23%) who did not know about their previous infection but had an anti-nucleocapsid T cell response were also considered virus-experienced. According to our results, no statistically significant difference was found between the two cohorts regarding the SARS-CoV-2-specific T cell response, neutralizing anti-RBD IgG, and anti-S IgA serum antibody levels either six or twelve months after receiving the booster, despite the overall higher median values of the first cohort. The only significant difference was the higher anti-S1/S2 IgG antibody level in the first cohort one year after the BNT162b2 booster (p = 0.039). In summary, the BNT162b2 and BBIBP-CorV boosters maintain durable humoral and T cell-mediated immune memory even one year after application. Although the booster provided limited protection against Omicron breakthrough infections, as 73.6% of these infections occurred after the booster vaccination, which means 53.5% cumulative incidence, it still offered excellent protection against severe disease and hospitalization in both cohorts.

Bayesian inference for prediction of survival probability inprime-boost vaccination regimes.

We focus on Bayesian inference for survival probabilities in a prime-boost vaccination regime in the development of an Ebola vaccine. We are interested in the heterologous prime-boost regimen (unmatched vaccine deliverys using the same antigen) due to its demonstrated durable immunity, well-tolerated safety profile, and suitability as a population vaccination strategy. Our research is motivated by the need to estimate the survival probability given the administered dosage. To do so, we establish two key relationships. Firstly, we model the connection between the designed dose concentration and the induced antibody count using a Bayesian response surface model. Secondly, we model the association between the antibody count and the probability of survival when experimental subjects are exposed to the Ebola virus in a controlled setting using a Bayesian probability of survival model. Finally, we employ a combination of the two models with dose concentration as the predictor of the survival probability for a future vaccinated population. We implement our two-level Bayesian model in Stan, and illustrate its use with simulated and real-world data. Performance of this model is evaluated via simulation. Our work offers a new application of drug synergy models to examine prime-boost vaccine efficacy, and does so using a hierarchical Bayesian framework that allows us to use dose concentration to predict survival probability.

Maternally Derived Antibodies to Foot-and-Mouth Disease Virus Modulate the Antigenic Specificity of Humoral Responses in Vaccinated Cattle.

Vaccination is widely used to control foot-and-mouth disease (FMD), but maternal antibodies may interfere with the response to vaccination in calves. This study, conducted on a regularly vaccinated Malaysian dairy farm, aimed to optimise the vaccination regime by measuring the in vitro neutralising virus antibody responses of 51 calves before and after vaccination with a one or two dose vaccination regime starting at 2-7 months old. The presence of maternal antibodies was associated with poor post-vaccination antibody responses after a single dose of vaccine in calves less than 6 months old. However, a second dose of vaccine given three weeks later, improved the antibody responses in all ages of calves. This confirms the view that in regularly vaccinated farms, some combination of delay and revaccination is needed to achieve effective immunization of calves. Sera from cows and pre-vaccinated calves neutralised homologous serotype A vaccine virus more strongly than a heterologous serotype A field virus, but this pattern was reversed in some calves after vaccination. The strength of heterologous responses in calves 49 days after first vaccination correlated to the amount of transferred maternal antibody, suggesting that pre-existing antibodies could have modulated the specificity of these active antibody responses. If confirmed, such an effect by pre-existing antibodies could have wider implications for broadening the coverage of FMD vaccine responses.