Human Vaccine Research Articles

Phylodynamic analysis revealed that human mobility and vaccination were correlated to the local spread of SARS-CoV-2 in Republic of Korea

ABSTRACT Following the global emergence of the SARS-CoV-2 Alpha variant of concern (VOC) in 2020, the Delta variant triggered another wave in 2021. The AY.69 lineage, a Delta VOC, was particularly prevalent in Republic of Korea (South Korea) from May 2021 to January 2022, despite the synchronized implementation of vaccination programmes and non-pharmaceutical interventions (NPIs) such as social distancing. In this study, we used phylogeographic analysis combined with a generalized linear model (GLM) to examine the impact of human movement and vaccination on viral transmission. Our findings indicated that transmission primarily originated in South Korea’s metropolitan areas, and a positive correlation was observed between total human mobility (tracked by GPS on mobile phones and estimated through credit card consumption) and viral spread. The phylodynamic analysis further revealed that non-vaccinated individuals were the primary transmitters of the virus during the study period, even though vaccination programmes had commenced three months prior to the AY.69 outbreak. Our study emphasizes the need to focus on controlling SARS-CoV-2 transmission in metropolitan regions and among unvaccinated populations. Furthermore, the positive correlation between mobility data and viral dissemination could contribute to the development of more accurate predictive models for local spread of pandemics.

Evaluation of Four Adjuvant Combinations, IVAX-1, IVAX-2, CpG-1826+Montanide ISA 720 VG and CpG-1018+Montanide ISA 720 VG, for Safety and for Their Ability to Elicit Protective Immune Responses in Mice against a Respiratory Challenge with Chlamydia muridarum.

There is an urgent need to produce a vaccine for Chlamydia trachomatis infections. Here, using the Chlamydia muridarum major outer membrane protein (MOMP) as an antigen, four adjuvant combinations IVAX-1 (MPLA+CpG-1018+AddaVax), IVAX-2 (MPLA+CpG-1018+AS03), CpG-1826+Montanide ISA 720 VG (CpG-1826+Mont) and CpG-1018+Montanide ISA 720 VG (CpG-1018+Mont), were tested for their local reactogenicity and ability to elicit protection in BALB/c mice against a respiratory challenge with C. muridarum. Immunization with IVAX-1 or IVAX-2 induced no significant local reactogenicity following intramuscular immunization. In contrast, vaccines containing Montanide resulted in the formation of a local granuloma. Based on the IgG2a/IgG1 ratio in serum, the four adjuvant combinations elicited Th1-biased responses. IVAX-1 induced the highest in vitro neutralization titers while CpG-1018+Mont stimulated the lowest. As determined by the levels of IFN-γ produced by T-cells, the most robust cellular immune responses were elicited in mice immunized with CpG-1018+Mont, while the weakest responses were mounted by mice receiving IVAX-1. Following the respiratory challenge, mice immunized with CpG-1018+Mont lost the least amount of body weight and had the lowest number of C. muridarum inclusion-forming units (IFUs) in the lungs, while those receiving IVAX-2 had lost the most weight and had the highest number of IFUs in their lungs. Animals vaccinated with CpG-1826+Mont had the lightest lungs while those immunized using IVAX-2 had the heaviest. To conclude, due to their safety and adjuvanticity, IVAX formulations should be considered for inclusion in human vaccines against Chlamydia.

Side-by-side Comparative Study of the Immunogenicity of the Intramuscular and Intradermal Rabies Post-exposure Prophylaxis Regimens in a Cohort of Suspected Rabies Virus Exposed Individuals.

All World Health Organization (WHO) pre-qualified rabies vaccines for humans are inactivated tissue culture rabies virus formulations produced for intramuscular (IM) administration. Due to costs and vaccine shortage, dose-saving intradermal (ID) administration of rabies post-exposure prophylaxis (PEP) is encouraged by WHO. This study compared the immunogenicity of the ID 2-site, 3-visit Institut Pasteur Cambodge (IPC) PEP regimen to the IM 1-site, 4-visit 4-dose Essen regimen using Verorab vaccine (Sanofi). The development of neutralizing antibodies (nAbs) and T cell response was assessed in 210 patients with a category II or III animal exposure in a rabies-endemic country. At day 28, all participants developed nAbs (≥0.5 IU/mL), irrespective of PEP scheme, age, or administration of rabies immunoglobulin. T cell response and nAb titers were similar for both PEP schemes. This study demonstrated that the 1-week ID IPC regimen is as effective as the 2-week IM 4-dose Essen regimen in inducing an anti-rabies immune response under real-life PEP.

Manejo desde atención primaria de la infección por la viruela del mono (MPOX) en humanos

Monkeypox (MPOX) is a viral zoonosis endemic in West or Central African countries that is sporadically exported to another area. In May 2022, a global outbreak of MPOX smallpox began to occur in several countries in Europe and North America. Most of the reported cases are identified at the outpatient level and mainly affect men who have sex with men (MSM). Transmission is by close contact with lesions, body fluids, respiratory secretions or contaminated material from an infected person or animal. The clinical picture is similar to human smallpox, with less severity. Mild, self-limiting skin involvement predominates after 2-4 weeks. In MSM, atypical skin lesions appear due to the mode of infection. Severe forms or complications may appear in certain risk groups. The case fatality rate is 3%-6% depending on the clade responsible. The diagnosis of suspicion is confirmed by detection of the virus from exudates of lesions or scabs, with nucleic acid amplification techniques by conventional or real-time PCR. Clinical management in most cases is performed in primary care (PC), by monitoring the main symptoms. Between 5-10% require hospital management and there are some specific antiviral treatment options. Human smallpox vaccines protect against MPOX and are used as pre- and post-exposure prophylaxis for persons at risk. Measures to reduce exposure to the virus are the main MPOX prevention strategy. In addition, the role of the family physician is key to controlling the spread of MPOX through active surveillance and early diagnosis of the disease.

Human Papiloma Virus Vaccination: Knowledge, Attitude and Practice Among Medical Students at Tertiary Care Hospital

Abstract Background:Cervical cancer is the leading cause of death in India. HPV virus is a major infectious etiological factor of cervical cancer. It has been proven that HPV vaccine, if taken before initiation of sexual life, is highly effective in HPV and cervical cancer prevention. Despite its availability, deaths due to cervical cancer has increased rapidly. Healthcare workers, especially the young medical students can play a significant role in recommendation of HPV vaccination among people. So, this study was conducted to study the knowledge, attitude and practices of HPV infection and vaccination among medical students. Methodology: A cross -sectional observational study was conducted in medical students of Narendra Modi Medical College. Three hundred medical students were requested to fill a questionnaire which covered demographic details, knowledge, attitude and practice towards HPV vaccination for cervical cancer prevention. Results:82.66% of students were aware about the HPV infection out of which 71% of the participants knew that cervical cancer can be prevented by HPV vaccine, 66.66% of studentes aware of the availability and 35% were well aware about the correct schedule/dosage of vaccination. Conclusion: Though the knowledge and attitude about the HPV infection and its vaccination is good among the medical students, but the practice of vaccination is poor. Keywords: HPV – Human Papilloma Virus, Knowledge, Attitude, Practice, HPV vaccine, medical students

Human Papiloma Virus Vaccination: Knowledge, Attitude and Practice Among Medical Students at Tertiary Care Hospital

Abstract Background: Cervical cancer is the leading cause of death in India. HPV virus is a major infectious etiological factor of cervical cancer. It has been proven that HPV vaccine, if taken before initiation of sexual life, is highly effective in HPV and cervical cancer prevention. Despite its availability, deaths due to cervical cancer has increased rapidly. Healthcare workers, especially the young medical students can play a significant role in recommendation of HPV vaccination among people. So, this study was conducted to study the knowledge, attitude and practices of HPV infection and vaccination among medical students. Methodology: A cross -sectional observational study was conducted in medical students of Narendra Modi Medical College. Three hundred medical students were requested to fill a questionnaire which covered demographic details, knowledge, attitude and practice towards HPV vaccination for cervical cancer prevention. Results:82.66% of students were aware about the HPV infection out of which 71% of the participants knew that cervical cancer can be prevented by HPV vaccine, 66.66% of studentes aware of the availability and 35% were well aware about the correct schedule/dosage of vaccination. Conclusion: Though the knowledge and attitude about the HPV infection and its vaccination is good among the medical students, but the practice of vaccination is poor. Keywords: HPV – Human Papilloma Virus, Knowledge, Attitude, Practice, HPV vaccine, medical students

Knowledge and Attitudes toward Human Papillomavirus and Vaccination: A Survey among Nursing Students in Saudi Arabia.

One of the most prevalent conditions affecting the vaginal organs is the human papilloma virus (HPV). Human papillomavirus (HPV) knowledge and attitudes have been the subject of numerous studies in Saudi Arabia. However, there are only a few studies that have examined university students' attitudes and knowledge of the human papillomavirus and the vaccine that is associated with it. To predict the level of knowledge and attitudes regarding HPV and its related vaccine among undergraduate nursing students. This was descriptive cross-sectional research. After being selected from Princess Nourah bint Abdulrahman University's College of Nursing, 307 nursing students agreed to take part and completed an online survey that was self-administered. The majority of the participants (73.5%) had a low level of knowledge of HPV with a mean score of 2.77 ± 1.78. In addition, more than half of the participating nursing students (57%) had a moderate attitude toward HPV vaccination with a mean score of 51.18 ± 11.16. The study results also verified that there was a highly significant correlation between the nursing students' demographics and their knowledge and attitudes toward HPV (p < 0.001). According to the SEM, nursing students' knowledge regarding HPV accounted for 48% of the variance in students' attitudes. Nursing students' knowledge regarding HPV vaccination is an important predictor of students' attitudes regarding HPV.

Humoral and cellular BNT162b2 mRNA-based booster vaccine-induced immunity in patients with multiple myeloma and persistence of neutralising antibodies: results of a prospective single-centre cohort study.

Currently available messenger ribonucleic acid (mRNA)-based vaccines against coronavirus disease (COVID-19) have been shown to be effective even in highly immunocompromised hosts, including patients with multiple myeloma. However, vaccination failure can be observed in all patient groups. This prospective study longitudinally assessed the humoral and cellular responses to a third booster dose of BNT162b2 mRNA-based vaccine in patients with myeloma (n = 59) and healthy controls (n = 22) by measuring the levels of anti-spike (S) antibodies (electro-chemiluminescence immunoassay) including neutralising antibodies and specific T-cells (enzyme-linked immunospot assay) following booster administration. The third booster dose showed a high immunogenicity on the serological level among the patients with multiple myeloma (median anti-S level = 41 binding antibody units [BAUs]/ml pre-booster vs 3902 BAU/ml post-booster, p <0.001; increase in the median neutralising antibody level from 19.8% to 97%, p <0.0001). Four of five (80%) patients with a complete lack of any serological response (anti-S immunoglobulin level <0.8 BAU/ml) after two vaccine doses developed detectable anti-S antibodies after booster vaccination (median anti-S level = 88 BAU/ml post-booster). T-cell responses were largely preserved among the patients with multiple myeloma with no difference from the healthy controls following baseline vaccination (median spot-forming units [SFU]/106of peripheral blood mononuclear cells = 193 vs 175, p = 0.711); these responses were augmented significantly after booster administration among the patients with multiple myeloma (median SFU/106of peripheral blood mononuclear cells = 235 vs 443, p <0.001). However, the vaccination responses remained highly heterogeneous and diminished over time, with insufficient serological responses occurring even after booster vaccination in a few patients irrespective of the treatment intensity. Our data demonstrate improvements in humoral and cellular immunity following booster vaccination and support the assessment of the humoral vaccine response in patients with multiple myeloma until a threshold for protection against severe COVID-19 is validated. This strategy can allow the identification of patients who might benefit from additional protective measures (e.g. pre-exposure prophylaxis via passive immunisation).

A temperature-dependent virus-binding assay reveals the presence of neutralizing antibodies in human cytomegalovirus gB vaccine recipients' sera.

Human cytomegalovirus (HCMV) remains an important cause of mortality in immune-compromised transplant patients and following congenital infection. Such is the burden, an effective vaccine strategy is considered to be of the highest priority. The most successful vaccines to date have focused on generating immune responses against glycoprotein B (gB) - a protein essential for HCMV fusion and entry. We have previously reported that an important component of the humoral immune response elicited by gB/MF59 vaccination of patients awaiting transplant is the induction of non-neutralizing antibodies that target cell-associated virus with little evidence of concomitant classical neutralizing antibodies. Here we report that a modified neutralization assay that promotes prolonged binding of HCMV to the cell surface reveals the presence of neutralizing antibodies in sera taken from gB-vaccinated patients that cannot be detected using standard assays. We go on to show that this is not a general feature of gB-neutralizing antibodies, suggesting that specific antibody responses induced by vaccination could be important. Although we can find no evidence that these neutralizing antibody responses are a correlate of protection in vivo in transplant recipients their identification demonstrates the utility of the approach in identifying these responses. We hypothesize that further characterization has the potential to aid the identification of functions within gB that are important during the entry process and could potentially improve future vaccine strategies directed against gB if they prove to be effective against HCMV at higher concentrations.

Development of HPV16 mouse and dog models for more accurate prediction of human vaccine efficacy

BackgroundAnimal models are essential to understand the physiopathology of human diseases but also to evaluate new therapies. However, for several diseases there is no appropriate animal model, which complicates the development of effective therapies. HPV infections, responsible for carcinoma cancers, are among these. So far, the lack of relevant animal models has hampered the development of therapeutic vaccines. In this study, we used a candidate therapeutic vaccine named C216, similar to the ProCervix candidate therapeutic vaccine, to validate new mouse and dog HPV preclinical models. ProCervix has shown promising results with classical subcutaneous murine TC-1 cell tumor isografts but has failed in a phase II study.ResultsWe first generated E7/HPV16 syngeneic transgenic mice in which the expression of the E7 antigen could be switched on through the use of Cre–lox recombination. Non-integrative LentiFlash® viral particles were used to locally deliver Cre mRNA, resulting in E7/HPV16 expression and GFP reporter fluorescence. The expression of E7/HPV16 was monitored by in vivo fluorescence using Cellvizio imaging and by local mRNA expression quantification. In the experimental conditions used, we observed no differences in E7 expression between C216 vaccinated and control groups. To mimic the MHC diversity of humans, E7/HPV16 transgenes were locally delivered by injection of lentiviral particles in the muscle of dogs. Vaccination with C216, tested with two different adjuvants, induced a strong immune response in dogs. However, we detected no relationship between the level of cellular response against E7/HPV16 and the elimination of E7-expressing cells, either by fluorescence or by RT-ddPCR analysis.ConclusionsIn this study, we have developed two animal models, with a genetic design that is easily transposable to different antigens, to validate the efficacy of candidate vaccines. Our results indicate that, despite being immunogenic, the C216 candidate vaccine did not induce a sufficiently strong immune response to eliminate infected cells. Our results are in line with the failure of the ProCervix vaccine that was observed at the end of the phase II clinical trial, reinforcing the relevance of appropriate animal models.

Efficacy and safety of combining PD-1 blockage and human papillomavirus vaccine for patients with relapsed/refractory advanced cervical cancer.

5530 Background: The prognosis for patients with relapsed/refractory advanced cervical cancer is dismal with a 5-year survival rate of 17%. Limited treatment options were available including platin based therapy, antiangiogenic therapy and immune therapy. Immune checkpoint blockage with anti-programmed cell death 1 (PD-1) antibodies had an overall response rate of 17% among a minority of patients. Recently a phase II study showed human papillomavirus (HPV) 16 vaccination amplified PD-1 antibodies in incurable HPV16 positive cancer with an ORR of 33%. But the study enrolled majority were oropharyngeal cancer patients (92%). Here, we designed and conducted phase II clinical trial to assess the efficacy and safety of combining anti-PD-1 antibody and HPV vaccination for patients with relapsed/refract cervical cancer. Methods: In this single-arm, single-center phase II clinical trial, patients with relapsed/refract cervical cancer were registered (NCT04096911) and enrolled from Dec, 2019 to Dec, 2022 in Department of Oncology, Northern Jiangsu People's Hospital, Yangzhou, China. All patients received prior radiation therapy and had at least one or more lines of therapies. Duration of follow up for censored patients was 36 months. The recombinant human papillomavirus quadrivalent vaccine (0.5ml) was given subcutaneously on day 0, third month, and 6th month. Anti-PD-1 antibody, 200mg was given intravenously every 3 weeks starting on day 1 for up to 2 years. Results: As of Dec 21, 2022, thirteen patients were enrolled in the trial. The median age was 55 years (range, 52 to 83 years). The overall response rate was 69.2%. Disease control rate was 84.9%. Median duration of response was 7.07 months (95%CI, 1.94 to 15.8 month). Six patients achieved complete response. Median overall survival was 13.96 month. No grade 3 and 4 toxicity occurred. Conclusions: Our study was the first clinical trial using HPV vaccine as therapeutic agent in advance cervical cancer treatment. Up to date, immunotherapy along in cervical cancer had limited response rate less than 20% and the combination therapies was less than 40%. In our study, the overall response of 69.2%, disease control rate of 84.9% and median overall survival of 13.96 months were significantly higher compared with anti-PD-1 antibody alone or any current available regiment combinations in relapsed/refract advance cervical cancer patients. We also found synergistic effect of T cell and B cell plays an important role in our study. It appears neoantigen associated with tumor was easier to initiate immune response in cervical cancer patients. This is the first time to show employing combined immune therapeutic agents only is a novel effective clinical strategy in relapsed/refract advance cervical cancer. Clinical trial information: NCT04096911 .

Eyelid Papilloma

A 69-year-old immunocompetent woman visited the ophthalmology clinic with a pink peduncular mass on the left lower eyelid margin, which was present for > 10 days. On examination, a 2 × 2-mm pink peduncular mass was observed on the left lower lid (A, asterisk). No history of papilloma, human papillomavirus infection vaccination (HPV), or eye injury was reported. The patient declined treatment for papilloma, including oral medications. She subsequently obtained the HPV 9-valent vaccine on her own accord, and after 2 doses of vaccine, (B) the papilloma spontaneously resolved within 2 months. (Magnified version of Figure A-B is available online at www.aaojournal.org).

Genetic variations of Plasmodium falciparum circumsporozoite protein and the impact on interactions with human immunoproteins and malaria vaccine efficacy.

In October 2021, the world's first malaria vaccine RTS,S was endorsed by WHO for broad use in children, despite its low efficacy. This study examined polyclonal infections and the associations of parasite genetic variations with binding affinity to human leukocyte antigen (HLA). Multiplicity of infection was determined by amplicon deep sequencing of PfMSP1. Genetic variations in PfCSP were examined across 88 samples from Ghana and analyzed together with 1655 PfCSP sequences from other African and non-African isolates. Binding interactions of PfCSP peptide variants and HLA were predicted using NetChop and HADDOCK. High polyclonality was detected among infections, with each infection harboring multiple non-3D7 PfCSP variants. Twenty-seven PfCSP haplotypes were detected in the Ghanaian samples, and they broadly represented PfCSP diversity across Africa. The number of genetic differences between 3D7 and non-3D7 PfCSP variants does not influence binding to HLA. However, CSP peptide length after proteolytic degradation significantly affects its molecular weight and binding affinity to HLA. Despite the high diversity of HLA, the majority of the HLAI and II alleles interacted/bound with all Ghana CSP peptides. Multiple non-3D7 strains among P. falciparum infections could impact the effectiveness of RTS,S. Longer peptides of the Th2R/Th3R CSP regions should be considered in future versions of RTS,S.

How Long Will It Take to Launch an Effective Helicobacter pylori Vaccine for Humans?

Helicobacter pylori infection often occurs in early childhood, and can last a lifetime if not treated with medication. H. pylori infection can also cause a variety of stomach diseases, which can only be treated with a combination of antibiotics. Combinations of antibiotics can cure H. pylori infection, but it is easy to relapse and develop drug resistance. Therefore, a vaccine is a promising strategy for prevention and therapy for the infection of H. pylori. After decades of research and development, there has been no appearance of any H. pylori vaccine reaching the market, unfortunately. This review summarizes the aspects of candidate antigens, immunoadjuvants, and delivery systems in the long journey of H. pylori vaccine research, and also introduces some clinical trials that have displayed encouraging or depressing results. Possible reasons for the inability of an H. pylori vaccine to be available over the counter are cautiously discussed and some propositions for the future of H. pylori vaccines are outlined.

EE211 Guidelines for the Economic Evaluation of Vaccination Programs in Canada

Canada’s National Advisory Committee on Immunization (NACI) makes recommendations on the use of human vaccines. Traditionally, NACI reviewed vaccine characteristics and disease burden. With its expanded mandate, NACI now considers cost-effectiveness via economic evaluations; thus, warranting guidelines. Existing guidelines are either not specific to the universal healthcare context, or not specific to vaccination programs.

Humoral vaccine response and breakthrough infections in kidney transplant recipients during the COVID-19 pandemic: a nationwide cohort study.

Kidney transplant recipients (KTRs) experienced reduced SARS-CoV-2 vaccine response and were at increased risk of severe COVID-19. It is unknown if level of vaccine induced anti-receptor binding domain IgG (anti-RBD IgG) correlates with protection from and survival following COVID-19. We aimed to evaluate the effect of vaccine response on risk of breakthrough infections (BTI) and COVID-19 death in KTRs. We performed a nationwide study, examining the competing risk of SARS-CoV-2 infection, COVID-19 related/unrelated death, and vaccine efficacy as assessed by level of anti-RBD IgG response 4-10 weeks after each vaccination. The study included all KTR in Norway alive and with a functioning graft on February 20th, 2020, and events after November 11th, 2022 were right-censored. A pre-pandemic reference-cohort from January 1st 2019 to January 1st 2020 was included to evaluate excess mortality. The study was conducted at Oslo University Hospital, Rikshospitalet, Norway. The study included 3607 KTRs (59 [48-70] years) with a functioning graft at February 20th, 2020, who received (median [IQR]) 4 [3-4] vaccines (range 2-6, 99% mRNA). Anti-RBD IgG was measured in 12701 serum samples provided by 3213 KTRs. Vaccine response was assessed 41 [31-57] days after vaccination. A total of 1090 KTRs were infected with SARS-CoV-2, 1005 (92%) were BTI, and vaccine response did not protect against BTI. The hazard ratio for COVID-19 related death 40 days post-infection was 1.71 (95% CI: 1.14, 2.56) comparing vaccine response levels (≥5 vs. ≥5000 BAU/mL). No excess non-COVID-19 mortality was registered in KTRs surviving SARS-CoV-2 infection compared to a 2019 pre-pandemic reference. Our findings suggested that SARS-CoV-2 mRNA vaccine response did not predict protection against infection, but prevention of fatal disease progression in KTRs and greater vaccine response further reduced the risk of COVID-19 death. No excess non-COVID-19 mortality was seen during the pandemic. CEPI and internal funds.

How to train your myeloid cells: a way forward for helminth vaccines?

Soil-transmitted helminths affect approximately 1.5 billion people worldwide. However, as no vaccine is currently available for humans, the current strategy for elimination as a public health problem relies on preventive chemotherapy. Despite more than 20 years of intense research effort, the development of human helminth vaccines (HHVs) has not yet come to fruition. Current vaccine development focuses on peptide antigens that trigger strong humoral immunity, with the goal of generating neutralizing antibodies against key parasite molecules. Notably, this approach aims to reduce the pathology of infection, not worm burden, with only partial protection observed in laboratory models. In addition to the typical translational hurdles that vaccines struggle to overcome, HHVs face several challenges (1): helminth infections have been associated with poor vaccine responses in endemic countries, probably due to the strong immunomodulation caused by these parasites, and (2) the target population displays pre-existing type 2 immune responses to helminth products, increasing the likelihood of adverse events such as allergy or anaphylaxis. We argue that such traditional vaccines are unlikely to be successful on their own and that, based on laboratory models, mucosal and cellular-based vaccines could be a way to move forward in the fight against helminth infection. Here, we review the evidence for the role of innate immune cells, specifically the myeloid compartment, in controlling helminth infections. We explore how the parasite may reprogram myeloid cells to avoid killing, notably using excretory/secretory (ES) proteins and extracellular vesicles (EVs). Finally, learning from the field of tuberculosis, we will discuss how anti-helminth innate memory could be harnessed in a mucosal-trained immunity-based vaccine.

Impact of human cooperation on vaccination behaviors

This paper studies a dynamic vaccination game model embedded with vaccine cost-effectiveness and dyadic game during an epidemic, assuming the appearance of cooperation among individuals from an evolutionary perspective. The infection dynamics of the individuals' states follow a modified S/VIS (susceptible/vaccinated-infected-susceptible) dynamics. Initially, we assume that the individuals are unsure about their infection status. Thus, they make decisions regarding their options based on their neighbors' perceptions, the prevalence of the disease, and the characteristics of the available vaccines. We then consider the strategy updating process IBRA (individuals-based risk assessment) concerning an individual's committing vaccination based on a neighbor's decision. In the perspective of social dilemma, it presents the idea of social efficiency deficit to find the gap between social optimum and Nash equilibrium point based on dilemma strength by considering vaccine decision. The cost and cooperative behavior depend on disease severity, neighbor's attitude, and vaccine properties to obtain a reduced-order optimal solution to control infectious diseases. Vaccine factors (efficiency, cost, and benefit) are crucial in changing human vaccine decisions and cooperative behavior. It turns out that, even in the prisoner's dilemma case, where all defection attitude occurs, vaccine uptake (cooperation) increases. Finally, extensive numerical studies were presented that illustrate interesting phenomena and investigate the ultimate extent of the epidemic, vaccination coverage, average social benefits, and the social efficiency deficit concerning optimal strategies and the dynamic vaccine attitudes of individuals.PACS numbers.Theory and modeling; computer simulation, 87.15. Aa; Dynamics of evolution, 87.23. Kg.

Addendum: Systems vaccinology of the BNT162b2 mRNA vaccine in humans.

Addendum: Systems vaccinology of the BNT162b2 mRNA vaccine in humans.

A first-in-human germline-targeting HIV nanoparticle vaccine induced broad and publicly targeted helper T cell responses.

The engineered outer domain germline targeting version 8 (eOD-GT8) 60-mer nanoparticle was designed to prime VRC01-class HIV-specific B cells that would need to be matured, through additional heterologous immunizations, into B cells that are able to produce broadly neutralizing antibodies. CD4 T cell help will be critical for the development of such high-affinity neutralizing antibody responses. Thus, we assessed the induction and epitope specificities of the vaccine-specific T cells from the IAVI G001 phase 1 clinical trial that tested immunization with eOD-GT8 60-mer adjuvanted with AS01B. Robust polyfunctional CD4 T cells specific for eOD-GT8 and the lumazine synthase (LumSyn) component of eOD-GT8 60-mer were induced after two vaccinations with either the 20- or 100-microgram dose. Antigen-specific CD4 T helper responses to eOD-GT8 and LumSyn were observed in 84 and 93% of vaccine recipients, respectively. CD4 helper T cell epitope "hotspots" preferentially targeted across participants were identified within both the eOD-GT8 and LumSyn proteins. CD4 T cell responses specific to one of these three LumSyn epitope hotspots were observed in 85% of vaccine recipients. Last, we found that induction of vaccine-specific peripheral CD4 T cells correlated with expansion of eOD-GT8-specific memory B cells. Our findings demonstrate strong human CD4 T cell responses to an HIV vaccine candidate priming immunogen and identify immunodominant CD4 T cell epitopes that might improve human immune responses either to heterologous boost immunogens after this prime vaccination or to other human vaccine immunogens.