scholarly journals HIV population-level adaptation can rapidly diminish the impact of a partially effective vaccine

2017 ◽  
Author(s):  
Joshua T. Herbeck ◽  
Kathryn Peebles ◽  
Paul T. Edlefsen ◽  
Morgane Rolland ◽  
James T. Murphy ◽  
...  
Keyword(s):  
Vaccination Coverage ◽  
Vaccine Efficacy ◽  
Vaccine Development ◽  
Vaccine Trial ◽  
Development Program ◽  
Population Level ◽  
Hiv Vaccine ◽  
Effective Vaccine ◽  
Vaccination Programs ◽  
The Impact

AbstractDevelopment of an HIV vaccine is essential to ending the HIV/AIDS pandemic. However, vaccines can result in the emergence and spread of vaccine-resistant strains. Indeed, analyses of breakthrough infections in the HIV vaccine trial RV144 identified HIV genotypes with differential rates of transmission in vaccine and placebo recipients. We hypothesized that, for HIV vaccination programs based on partially effective vaccines similar to RV144, HIV adaptation will diminish the expected vaccine impact. Using two HIV epidemic models, we simulated large-scale vaccination programs and, critically, included HIV strain diversity with respect to the vaccine response. We show here that rapid population-level viral adaptation can lead to decreased overall vaccine efficacy and substantially fewer infections averted by vaccination, when comparing scenarios with and without viral evolution (depending on vaccination coverage, vaccine efficacy against the sensitive allele, and the initial resistant allele frequency). Translating this to the epidemic in South Africa, a scenario with 70% vaccination coverage may result in 250,000 new infections within 10 years of vaccine rollout that are due solely to HIV adaptation, all else being equal. These findings suggest that approaches to HIV vaccine development, program implementation, and epidemic modeling may require attention to viral evolutionary responses to vaccination.

scholarly journals Intention to Be Vaccinated for COVID-19 among Italian Nurses during the Pandemic

Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 500
Author(s):  
Marco Trabucco Aurilio ◽  
Francesco Saverio Mennini ◽  
Simone Gazzillo ◽  
Laura Massini ◽  
Matteo Bolcato ◽  
...  
Keyword(s):  
Vaccine Efficacy ◽  
Online Survey ◽  
Vaccine Development ◽  
Vaccine Coverage ◽  
World Health ◽  
Vaccine Hesitancy ◽  
Effective Vaccine ◽  
Online Questionnaire ◽  
Cross Sectional ◽  
Female Sex

Background: While the COVID-19 pandemic has spread globally, health systems are overwhelmed by both direct and indirect mortality from other treatable conditions. COVID-19 vaccination was crucial to preventing and eliminating the disease, so vaccine development for COVID-19 was fast-tracked worldwide. Despite the fact that vaccination is commonly recognized as the most effective approach, according to the World Health Organization (WHO), vaccine hesitancy is a global health issue. Methods: We conducted a cross-sectional online survey of nurses in four different regions in Italy between 20 and 28 December 2020 to obtain data on the acceptance of the upcoming COVID-19 vaccination in order to plan specific interventions to increase the rate of vaccine coverage. Results: A total of 531 out of the 5000 nurses invited completed the online questionnaire. Most of the nurses enrolled in the study (73.4%) were female. Among the nurses, 91.5% intended to accept vaccination, whereas 2.3% were opposed and 6.2% were undecided. Female sex and confidence in vaccine efficacy represent the main predictors of vaccine intention among the study population using a logistic regression model, while other factors including vaccine safety concerns (side effects) were non-significant. Conclusions: Despite the availability of a safe and effective vaccine, intention to be vaccinated was suboptimal among nurses in our sample. We also found a significant number of people undecided as to whether to accept the vaccine. Contrary to expectations, concerns about the safety of the vaccine were not found to affect the acceptance rate; nurses’ perception of vaccine efficacy and female sex were the main influencing factors on attitudes toward vaccination in our sample. Since the success of the COVID-19 immunization plan depends on the uptake rate, these findings are of great interest for public health policies. Interventions aimed at increasing employee awareness of vaccination efficacy should be promoted among nurses in order to increase the number of vaccinated people.

Effect of COVID-19 on vaccination coverage in Brazil

2021 ◽  
Vol 70 (11) ◽  
Author(s):  
Marcelle Moura Silveira ◽  
Neida Lucia Conrad ◽  
Fábio Pereira Leivas Leite
Keyword(s):  
Vaccination Coverage ◽  
Physical Distance ◽  
Disease Notification ◽  
Notification System ◽  
Vaccination Programs ◽  
Vaccine Preventable Diseases ◽  
Antigen Vaccine ◽  
Restricted Mobility ◽  
Consistent Information ◽  
The Impact

During the COVID-19 pandemic, recommendations for maintaining physical distance, restricted mobility measures, as well as fear of mass transmission by going to health centers have significantly contributed to the general vaccination coverage, which by and large is decreasing worldwide; thus, favoring the potential re-emergence of vaccine-preventable diseases. In this study, we have used the existing data on vaccination coverage during the pre-pandemic (2019) as well as the pandemic (2020) period to evaluate the impact of coronavirus outbreaks during the vaccination drive in Brazil. Furthermore, we have accumulated data since 2015 among the different regions of the country to acquire more consistent information. The various vaccines analyzed in our study were meningococcal C conjugate, Triple antigen vaccine, 10-valent pneumococcal conjugate, and BCG; subsequently, the data were obtained from the National Disease Notification System. This study revealed that the ongoing immunization drive saw a steep decline of around 10 to 20% during the (2019–2020) pandemic period in Brazil. These results provide strong evidence towards the decreasing trends following the vaccination programs during the COVID-19 pandemic period in Brazil. Furthermore, our results also highlight the importance of adopting widespread multi-component interventions to improve vaccination uptake rates.

scholarly journals Mucosal immune stimulation with HSV-2 and polyICLC boosts control of viremia in SIVΔNef vaccinated rhesus macaques with breakthrough SIV infection

2020 ◽  
Author(s):  
Meropi Aravantinou ◽  
Olga Mizenina ◽  
Thilo Brill ◽  
Jessica Kenney ◽  
Christine Timmons ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Immune Activation ◽  
Vaccine Efficacy ◽  
Cd4 T Cells ◽  
Hiv Vaccine ◽  
Live Attenuated Vaccine ◽  
Siv Infection ◽  
The Impact

ABSTRACTDevelopment of an effective human immunodeficiency virus (HIV) vaccine is among the highest priorities in the biomedical research agenda. Adjuvants enhance vaccine efficacy, but in the case of HIV, strong or inappropriate immune activation may undermine protection by increasing HIV susceptibility. Co-infection with immunomodulatory pathogens may also impact vaccine efficacy. In the rhesus macaque rectal SIVΔNef live attenuated vaccine model, we utilized a low virulence HSV-2 infection and the double-stranded RNA viral mimic polyICLC as tools to probe the effects of distinct types of immune activation on HIV vaccine efficacy and explore novel correlates of protection from wild type SIV. Rectally administered HSV-2 and polyICLC impacted the protection conferred by mucosal SIVΔNef vaccination by favoring partial protection in animals with breakthrough infection following virulent SIV challenge (“Controllers”). However, SIVΔNef persistence in blood and tissues did not predict protection in this rectal immunization and challenge model. Non-controllers had similar SIVΔNef viremia as completely protected macaques, and while they tended to have less replication competent SIVΔNef in lymph nodes, controllers had no recoverable virus in the lymph nodes. Non-controllers differed from protected macaques immunologically by having a greater frequency of pro-inflammatory CXCR3+CCR6+ CD4 T cells in blood and a monofunctional IFNγ-dominant CD8 T cell response in lymph nodes. Controller phenotype was associated with heightened IFNα production during acute SIV infection and a greater frequency of CXCR5+ CD4 T cells in blood pre-challenge despite a lower frequency of cells with the T follicular helper (Tfh) cell phenotype in blood and lymph nodes. Our results establish novel correlates of immunological control of SIV infection while reinforcing the potential importance of T cell functionality and location in SIVΔNef efficacy. Moreover, this work highlights that triggering of mucosal immunity can aid mucosal vaccine strategies rather than undermine protection.AUTHOR SUMMARYAn efficacious HIV vaccine is essential to contain the HIV pandemic. Vaccine-mediated protection from HIV may be either enhanced or obstructed by mucosal immune activation; thus, the impact of adjuvants and underlying co-infections that lead to immune activation needs to be evaluated. Using the SIV macaque model, we set out to study the impact of underlying infection with HSV-2 or treatment with the adjuvant polyICLC on rectal immunization with the live attenuated vaccine SIVΔNef. We found that neither stimulus impacted complete protection from SIV; however, the combination of HSV-2 and polyICLC improved control of infection in animals that were not completely protected. Compared with non-controller macaques, controllers had less inflammatory T cells before SIV challenge as well as greater gene expression of IFNα and more functional SIV-specific T cells after infection. The results add to our understanding of the mechanisms of SIVΔNef protection and demonstrate that mucosal immune activation does not necessarily undermine protection in mucosal vaccination against HIV.

scholarly journals V2-Specific Antibodies in HIV-1 Vaccine Research and Natural Infection: Controllers or Surrogate Markers

Animals ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 526 ◽  
Author(s):  
Duerr ◽  
Gorny
Keyword(s):  
Vaccine Efficacy ◽  
Natural Infection ◽  
Vaccine Trial ◽  
Clinical Findings ◽  
Hiv Vaccine ◽  
Model Systems ◽  
Potential Contribution ◽  
Vaccine Research ◽  
Specific Antibodies ◽  
Hiv 1

Most human immunodeficiency virus (HIV) vaccine trials have lacked efficacy and empirical vaccine lead targets are scarce. Thus far, the only independent correlate of reduced risk of HIV-1 acquisition in humans is elevated levels of V2-specific antibodies identified in the modestly protective RV144 vaccine trial. Ten years after RV144, human and non-human primate vaccine studies have reassessed the potential contribution of V2-specific antibodies to vaccine efficacy. In addition, studies of natural HIV-1 infection in humans have provided insight into the development of V1V2-directed antibody responses and their impact on clinical parameters and disease progression. Functionally diverse anti-V2 monoclonal antibodies were isolated and their structurally distinct V2 epitope regions characterized. After RV144, a plethora of research studies were performed using different model systems, immunogens, protocols, and challenge viruses. These diverse studies failed to provide a clear picture regarding the contribution of V2 antibodies to vaccine efficacy. Here, we summarize the biological functions and clinical findings associated with V2-specific antibodies and discuss their impact on HIV vaccine research.

scholarly journals Rectal Acquisition of Simian Immunodeficiency Virus (SIV) SIVmac239 Infection despite Vaccine-Induced Immune Responses against the Entire SIV Proteome

2020 ◽  
Vol 94 (24) ◽  
Author(s):  
Mauricio A. Martins ◽  
Lucas Gonzalez-Nieto ◽  
Michael J. Ricciardi ◽  
Varian K. Bailey ◽  
Christine M. Dang ◽  
...  
Keyword(s):  
T Cells ◽  
Virus Infection ◽  
Immune Responses ◽  
Simian Immunodeficiency Virus ◽  
Vaccine Efficacy ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Hiv Vaccine ◽  
Partial Control ◽  
Immunodeficiency Virus

ABSTRACT Given the complex biology of human immunodeficiency virus (HIV) and its remarkable capacity to evade host immune responses, HIV vaccine efficacy may benefit from the induction of both humoral and cellular immune responses of maximal breadth, potency, and longevity. Guided by this rationale, we set out to develop an immunization protocol aimed at maximizing the induction of anti-Envelope (anti-Env) antibodies and CD8+ T cells targeting non-Env epitopes in rhesus macaques (RMs). Our approach was to deliver the entire simian immunodeficiency virus (SIV) proteome by serial vaccinations. To that end, 12 RMs were vaccinated over 81 weeks with DNA, modified vaccinia Ankara (MVA), vesicular stomatitis virus (VSV), adenovirus type 5 (Ad5), rhesus monkey rhadinovirus (RRV), and DNA again. Both the RRV and the final DNA boosters delivered a near-full-length SIVmac239 genome capable of assembling noninfectious SIV particles and inducing T-cell responses against all nine SIV proteins. Compared to previous SIV vaccine trials, the present DNA-MVA-VSV-Ad5-RRV-DNA regimen resulted in comparable levels of Env-binding antibodies and SIV-specific CD8+ T-cells. Interestingly, one vaccinee developed low titers of neutralizing antibodies (NAbs) against SIVmac239, a tier 3 virus. Following repeated intrarectal marginal-dose challenges with SIVmac239, vaccinees were not protected from SIV acquisition but manifested partial control of viremia. Strikingly, the animal with the low-titer vaccine-induced anti-SIVmac239 NAb response acquired infection after the first SIVmac239 exposure. Collectively, these results highlight the difficulties in eliciting protective immunity against immunodeficiency virus infection. IMPORTANCE Our results are relevant to HIV vaccine development efforts because they suggest that increasing the number of booster immunizations or delivering additional viral antigens may not necessarily improve vaccine efficacy against immunodeficiency virus infection.

scholarly journals Modelling the household-level impact of a maternal respiratory syncytial virus (RSV) vaccine in a high-income setting

BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Patricia T. Campbell ◽  
Nicholas Geard ◽  
Alexandra B. Hogan
Keyword(s):  
Respiratory Syncytial Virus ◽  
Vaccine Trial ◽  
Population Level ◽  
High Income ◽  
Demographic Model ◽  
Model Framework ◽  
Substantial Impact ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
The Impact

Abstract Background Respiratory syncytial virus (RSV) infects almost all children by the age of 2 years, with the risk of hospitalisation highest in the first 6 months of life. Development and licensure of a vaccine to prevent severe RSV illness in infants is a public health priority. A recent phase 3 clinical trial estimated the efficacy of maternal vaccination at 39% over the first 90 days of life. Households play a key role in RSV transmission; however, few estimates of population-level RSV vaccine impact account for household structure. Methods We simulated RSV transmission within a stochastic, individual-based model framework, using an existing demographic model, structured by age and household and parameterised with Australian data, as an exemplar of a high-income country. We modelled vaccination by immunising pregnant women and explicitly linked the immune status of each mother-infant pair. We quantified the impact on children for a range of vaccine properties and uptake levels. Results We found that a maternal immunisation strategy would have the most substantial impact in infants younger than 3 months, reducing RSV infection incidence in this age group by 16.6% at 70% vaccination coverage. In children aged 3–6 months, RSV infection was reduced by 5.3%. Over the first 6 months of life, the incidence rate for infants born to unvaccinated mothers was 1.26 times that of infants born to vaccinated mothers. The impact in older age groups was more modest, with evidence of infections being delayed to the second year of life. Conclusions Our findings show that while individual benefit from maternal RSV vaccination could be substantial, population-level reductions may be more modest. Vaccination impact was sensitive to the extent that vaccination prevented infection, highlighting the need for more vaccine trial data.

Genetically identical primate modelling systems for HIV vaccines

1998 ◽  
Vol 10 (8) ◽  
pp. 651 ◽  
Author(s):  
Stephen J. Kent ◽  
Ian M. Lewis
Keyword(s):  
Immune Responses ◽  
Hiv Infection ◽  
Vaccine Development ◽  
Careful Consideration ◽  
Hiv Vaccine ◽  
Effective Vaccine ◽  
Hiv Vaccines ◽  
Major Step ◽  
Immunodeficiency Virus ◽  
Hiv 1

There is an urgent need for a safe and effective vaccine to prevent human immunodeficiency virus (HIV) infection. Several HIV vaccine candidates have shown promise, but many concerns regarding the safety and efficacy of current vaccines remain. A major hindrance in HIV vaccine development is a poor understanding of precisely what functions HIV vaccines are required to perform in order to protect humans from HIV-1. Only higher primates (i.e. macaques, chimpanzees and humans) are susceptible to HIV-1 or the closely related virus ‘simian immunodeficiency virus’. These species are outbred and there are remarkable genetic differences in both the immune responses to vaccines and their susceptibility to infection. The development of genetically identical macaques would be a major step towards dissecting what immune responses are required to protect from HIV infection. For example, live attenuated HIV-1 vaccines are likely to be highly efficacious, but will induce disease in a substantial proportion of recipients. Defining why a live attenuated vaccine is effective should allow safer vaccines to be developed, retaining only the immunologic properties of an effective vaccine. The reduction in ‘background genetic noise’ obtained by studying genetically identical primates would provide concise answers to critical HIV vaccine issues, by studying a minimal number of animals. Such an approach could potentially be employed in other diseases where non-human primates are the only available model. Small studies can be performed where identical twins are generated by embryo bisection; however, larger studies where multiple immune parameters are simultaneously evaluated would be facilitated by cloning technology. Despite the technical difficulties to be overcome, the potential gains in human health from the development of genetically identical non-human primates are worthy of careful consideration.

scholarly journals Identifying silent COVID-19 infections among children is critical for controlling the pandemic

2021 ◽  
Author(s):  
Seyed M. Moghadas ◽  
Meagan C. Fitzpatrick ◽  
Affan Shoukat ◽  
Kevin Zhang ◽  
Alison P. Galvani
Keyword(s):  
Vaccination Coverage ◽  
Vaccine Efficacy ◽  
The United States ◽  
Sensitivity Analyses ◽  
Transmission Model ◽  
Base Case ◽  
Age Group ◽  
One Year ◽  
The Impact ◽  
Targeted Approach

Importance: A significant proportion of COVID-19 transmission occurs silently during the pre-symptomatic and asymptomatic stages of infection. Children, while being important drivers of silent transmission, are not included in COVID-19 vaccination campaigns given their exclusion from clinical trials thus far. Objective: To investigate the impact of a targeted approach to identifying silent infections among children as a proxy for their vaccination. Design: This study used an age-structured disease transmission model to simulate the synergistic impact of interventions in reducing attack rates over the course of one year. Setting: A synthetic population representative of the demographics of the United States (US). Participants: Six age groups of 0-4, 5-10, 11-18, 19-49, 50-64, 65+ years old, stratified for their population size based on US census data. Exposures: Vaccination of adults, self-isolation of all symptomatic cases within 24 hours of symptom onset, and detection of silent infections. Main Outcomes and Measures: Vaccination of adults was implemented to reach a 40% coverage over the course of one year with a vaccine efficacy of 95% against symptomatic and severe COVID-19. Without vaccination of children, we determined the proportion and speed that would be required for identifying silent infections among this age group to suppress future attack rates below 5%. Results: A targeted approach that identifies 20.6% and 28.6% of silent infections among children within 2 or 3 days post-infection, respectively, would be required to bring attack rates under 5% with vaccination of adults. If silent infections among children remained undetected, achieving the same attack rates would require an unrealistically high vaccination coverage (at least 82%) of this age group, in addition to the base-case 40% vaccination coverage of adults. The results were robust in sensitivity analyses with respect to vaccine efficacy against infection and reduced susceptibility of children to infection. Conclusions and Relevance: In the absence of vaccine availability for children, a targeted approach to rapid identification of silent COVID-19 infections in this age group can significantly mitigate disease burden. Without measures to interrupt transmission chains from silent infections, vaccination of adults is unlikely to contain the outbreaks in the near term.

scholarly journals Impacts of Coronavirus on Farm and Pet Animals

2020 ◽  
Author(s):  
Sachin Subedi ◽  
Sulove Koirala ◽  
Lilong Chai
Keyword(s):  
Infectious Bronchitis Virus ◽  
Vaccine Development ◽  
Rna Virus ◽  
Farm Animals ◽  
Effective Vaccine ◽  
Nasal Discharge ◽  
Infectious Bronchitis ◽  
Gastrointestinal Lesions ◽  
On Farm ◽  
The Impact

Coronaviruses are positive sense RNA virus belonging to the Coronaviridae family, which are further subdivided into four genera: Alpha, Beta, Gamma, and Delta Coronaviruses. Infectious bronchitis virus and SARS-CoV belong to Beta Coronaviridae family. Infectious bronchitis virus causes respiratory and nephritic signs that includes tracheal rales, urate crystals, lethargy and nasal discharge. In livestock and pets, the Coronavirus infection causes mostly gastrointestinal lesions, which may be prevented through vaccination and biosecurity. Recent infections of SARS-CoV-2 (also known as COVID-19) on farm and pet animals were summarized in this study. Besides, zoo animals were reported with infections in some countries/regions. Although the damage of COVID-19 has not been reported as serious as highly pathogenic avian influenza (HPAI) and African Swine Fever (ASF) on farm animals so far, the transmission mechanism of COVID-19 among group animals/farms and its long-term impacts are still not clear. The impact of Coronavirus on animals and potential prevention strategies, such as vaccine development and farm biosecurity measures, were discussed. Prior to the development of the effective vaccine, the biosecurity measures (e.g., conventional disinfection strategies and innovated technologies) may play roles in preventing potential spread of diseases/viruses.

scholarly journals Quantifying the Impact of Public Perceptions on Vaccine Acceptance Using Behavioral Economics

2020 ◽  
Vol 8 ◽  
Author(s):  
Steven R. Hursh ◽  
Justin C. Strickland ◽  
Lindsay P. Schwartz ◽  
Derek D. Reed
Keyword(s):  
Behavioral Economics ◽  
Vaccine Efficacy ◽  
Development Process ◽  
Vaccine Development ◽  
Rapid Development ◽  
Public Perceptions ◽  
Mixed Effect ◽  
Behavioral Economic ◽  
Vaccine Acceptance ◽  
The Impact

This study was conducted to evaluate the impact of public perceptions of vaccine safety and efficacy on intent to seek COVID-19 vaccination using hypothetical vaccine acceptance scenarios. The behavioral economic methodology could be used to inform future public health vaccination campaigns designed to influence public perceptions and improve public acceptance of the vaccine. In June 2020, 534 respondents completed online validated behavioral economic procedures adapted to evaluate COVID-19 vaccine demand in relation to a hypothetical development process and efficacy. An exponential demand function was used to describe the proportion of participants accepting the vaccine at each efficacy. Linear mixed effect models evaluated development process and individual characteristic effects on minimum required vaccine efficacy required for vaccine acceptance. The rapid development process scenario increased the rate of decline in acceptance with reductions in efficacy. At 50% efficacy, 68.8% of respondents would seek the standard vaccine, and 58.8% would seek the rapid developed vaccine. Rapid vaccine development increased the minimum required efficacy for vaccine acceptance by over 9 percentage points, γ = 9.36, p < 0.001. Past-3-year flu vaccination, γ = −23.00, p < 0.001, and male respondents, γ = −4.98, p = 0.037, accepted lower efficacy. Respondents reporting greater conspiracy beliefs, γ = 0.39, p < 0.001, and political conservatism, γ = 0.32, p < 0.001, required higher efficacy. Male, γ = −4.43, p = 0.013, and more conservative, γ = −0.09, p = 0.039, respondents showed smaller changes in minimum required efficacy by development process. Information on the vaccine development process, vaccine efficacy, and individual differences impact the proportion of respondents reporting COVID-19 vaccination intentions. Behavioral economics provides an empirical method to estimate vaccine demand to target subpopulations resistant to vaccination.

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