Perceptions and Acceptance of a Prophylactic Vaccine for Human Immunodeficiency Virus (HIV): A Qualitative Study.

BACKGROUND: Despite advances in human immunodeficiency virus (HIV) prevention methods, such as the advent of pre-exposure prophylaxis (PrEP), the number of people with newly acquired HIV remains high, particularly in at-risk groups. A prophylactic HIV vaccine could contribute to reduced disease prevalence and future transmission and address limitations of existing options, such as suboptimal long-term adherence to PrEPs. METHODS: This qualitative study aimed to capture perceptions towards and acceptance of prophylactic HIV vaccination in three adult populations in the United States: the general population, 'at-risk' individuals (e.g. men who have sex with men, transgender individuals, gender-nonconforming individuals, and individuals in a sexual relationship with a person living with HIV), and parents/caregivers of children aged 9-17 years. Interviews were conducted with 55 participants to explore key drivers and barriers to HIV vaccine uptake, and a conceptual model was developed. RESULTS: The sample was diverse; participants were 51% female, aged 20-57 years (mean 37 years), 33% with high school diploma as highest education level, and identified as White (42%), Black or African American (35%), of Hispanic, Latino, or Spanish origin (22%), or other races/ethnicities (8%) [groupings are not mutually exclusive]. Perceptions were influenced by individual, interpersonal, community, institutional, and structural factors. Overall, 98% of participants thought vaccination would be beneficial in preventing HIV. Key considerations/barriers included perceived susceptibility, i.e. whether participants felt there was a risk of contracting HIV (discussed by 90%); the clinical profile of the vaccine (e.g. the adverse effect profile [98%], and vaccine efficacy [85%], cost [73%] and administration schedule [88%]); and concerns around potential vaccine-induced seropositivity (VISP; 62%). Stigma was not found to be an important barrier, with a general view that vaccination status was personal. Participants in the 'at-risk' group were the most likely to accept an HIV vaccine (70%). Unique concerns in the subgroups included how a potential vaccine's clinical profile compared with PrEP, voiced by those receiving/considering PrEP, and considerations of children's views on the topic, voiced by parents/caregivers. CONCLUSIONS: Understanding these factors could help develop HIV vaccine research strategies and contribute toward public health messaging to support future HIV vaccination programs.

HIV Diagnostics and Vaccines: It Takes Two to Tango.

Current serological tests for HIV screening and confirmation of infection present challenges to the adoption of HIV vaccines. The detection of vaccine-induced HIV-1 antibodies in the absence of HIV-1 infection, referred to as vaccine-induced seropositivity/seroreactivity, confounds the interpretation of test results, causing misclassification of HIV-1 status with potential affiliated stigmatization. For HIV vaccines to be widely adopted with high community confidence and uptake, tests that are agnostic to vaccination status (i.e., only positive for true HIV-1 infection) of tested individuals are needed. Successful development and deployment of such tests will require HIV vaccine developers to work in concert with diagnostic developers. Such tests will need to match today's high-performance standards (accuracy, cost-effectiveness, simplicity) for use in both vaccinated and unvaccinated populations, especially in low- and middle-income countries with high HIV burden. Herein, we discuss the challenges and strategies for developing modified serological HIV tests for concurrent deployment with HIV vaccines.

Geographic and Population Distributions of Human Immunodeficiency Virus (HIV)-1 and HIV-2 Circulating Subtypes: A Systematic Literature Review and Meta-analysis (2010-2021).

BACKGROUND: HIV poses significant challenges for vaccine development due to its high genetic mutation and recombination rates. Understanding the distribution of HIV subtypes (clades) across regions and populations is crucial. In this study, a systematic review of the past decade was conducted to characterize HIV-1/HIV-2 subtypes. METHODS: A comprehensive search was performed in PubMed, EMBASE, and CABI Global Health, yielding 454 studies from 91 countries. RESULTS: Globally, circulating recombinant forms (CRFs)/unique recombinant forms (URFs) accounted for 29% of HIV-1 strains, followed by subtype C (23%) and subtype A (17%). Among studies reporting subtype breakdowns in key populations, 62% of HIV infections among men who have sex with men (MSM) and 38% among people who inject drugs (PWIDs) were CRF/URFs. Latin America and the Caribbean exhibited a 25% increase in other CRFs (excluding CRF01_AE or CRF02_AG) prevalence between 2010-2015 and 2016-2021. CONCLUSIONS: This review underscores the global distribution of HIV subtypes, with an increasing prevalence of CRFs and a lower prevalence of subtype C. Data on HIV-2 were limited. Understanding subtype diversity is crucial for vaccine development, which need to elicit immune responses capable of targeting various subtypes. Further research is needed to enhance our knowledge and address the challenges posed by HIV subtype diversity.

Towards Novel HIV-1 Serodiagnostic Tests without Vaccine-Induced Seroreactivity.

Vaccine-induced seroreactivity/positivity (VISR/P) poses a significant and common challenge to HIV vaccine implementation, as up to 95% of vaccine recipients may be misclassified as having HIV infection by current HIV screening and confirmatory serological assays. We investigated whether internal HIV proteins could be used to overcome VISR and discovered a set of 4 antigens (gp41 endodomain, p31 integrase, p17 matrix protein, and Nef) that are recognized by antibodies produced in individuals with HIV infection but not in vaccinated individuals. When evaluated in a multiplex double-antigen bridging ELISA, this antigen combination had specificities of 98.1% prevaccination and 97.1% postvaccination, demonstrating the assay is minimally impacted by vaccine-induced antibodies. The sensitivity was 98.5%, further increasing to 99.7% when p24 antigen testing was included. Results were similar across HIV-1 clades. Although more technical advancements will be desired, this research provides the groundwork for the development of new fourth-generation HIV tests unaffected by VISR. IMPORTANCE While the detection of HIV infection is accomplished by several methods, the most common are serological tests that detect host antibodies produced in response to viral infection. However, the use of current serological tests may present a significant challenge to the adoption of an HIV vaccine in the future because the antibodies to HIV antigens detected in currently available tests also tend to be included as antigens in the HIV vaccines in development. The use of these serological tests may thus result in the misclassification of vaccinated HIV-negative individuals, which can have potential for significant harms for individuals and could prevent the widespread adoption and implementation of HIV vaccines. Our study aimed to identify and evaluate target antigens for inclusion in new serological tests that can be used to identify HIV infections without interference from vaccine-induced antibodies but also fit within existing platforms for HIV diagnostics.

Macroeconomic impact of Ebola outbreaks in Sub-Saharan Africa and potential mitigation of GDP loss with prophylactic Ebola vaccination programs.

INTRODUCTION: Decisions about prevention of and response to Ebola outbreaks require an understanding of the macroeconomic implications of these interventions. Prophylactic vaccines hold promise to mitigate the negative economic impacts of infectious disease outbreaks. The objective of this study was to evaluate the relationship between outbreak size and economic impact among countries with recorded Ebola outbreaks and to quantify the hypothetical benefits of prophylactic Ebola vaccination interventions in these outbreaks. METHODS: The synthetic control method was used to estimate the causal impacts of Ebola outbreaks on per capita gross domestic product (GDP) of five countries in sub-Saharan Africa that have previously experienced Ebola outbreaks between 2000 and 2016, where no vaccines were deployed. Using illustrative assumptions about vaccine coverage, efficacy, and protective immunity, the potential economic benefits of prophylactic Ebola vaccination were estimated using the number of cases in an outbreak as a key indicator. RESULTS: The impact of Ebola outbreaks on the macroeconomy of the selected countries led to a decline in GDP of up to 36%, which was greatest in the third year after the onset of each outbreak and increased exponentially with the size of outbreak (i.e., number of reported cases). Over three years, the aggregate loss estimated for Sierra Leone from its 2014-2016 outbreak is estimated at 16.1 billion International$. Prophylactic vaccination could have prevented up to 89% of an outbreak's negative impact on GDP, reducing the outbreak's impact to as little as 1.6% of GDP lost. CONCLUSION: This study supports the case that macroeconomic returns are associated with prophylactic Ebola vaccination. Our findings support recommendations for prophylactic Ebola vaccination as a core component of prevention and response measures for global health security.

Model-based evaluation of the impact of prophylactic vaccination applied to Ebola epidemics in Sierra Leone and Democratic Republic of Congo.

BACKGROUND: Protection by preventive Ebola vaccines has been demonstrated in clinical trials, but a complete picture of real-world effectiveness is lacking. Our previous study modeling the impact of preventively vaccinating healthcare workers (HCW) alone or with a proportion of the general population (GP) estimated significant reductions in incidence and mortality. The model assumed 100% vaccine efficacy, which is unlikely in the real world. We enhanced this model to account for lower vaccine efficacy and to factor in reduced infectiousness and lower case fatality rate in vaccinated individuals with breakthrough infections. METHODS: The previous model was enhanced to still permit a risk, although lower, for vaccinated individuals to become infected. The enhanced model, calibrated with data from epidemics in Sierra Leone (SL) and North Kivu, Democratic Republic of the Congo, helped evaluate the impact of preventive Ebola vaccination in different scenarios based on different vaccine efficacy rates (90% and 30% reductions in infection risk in the base and conservative scenarios, respectively; additionally, both scenarios with 50% reductions in infectiousness and mortality) and vaccination coverage among HCWs (30%, 90%) and GP (0%, 5%, and 10%). RESULTS: The base scenario estimated that, depending upon the proportions of vaccinated HCWs and GP, 33-85% of cases and 34-87% of deaths during the 2014 SL epidemic and 42-89% of cases and 41-89% of deaths during the 2018 North Kivu epidemic would be averted versus no vaccination. Corresponding estimates for the conservative scenario were: 23-74% of cases and 23-77% of deaths averted during the SL epidemic and 31-80% of both cases and deaths averted during the North Kivu epidemic. CONCLUSIONS: Preventive vaccination targeting HCW alone or with GP may significantly reduce the size and mortality of an EVD outbreak, even with modest efficacy and coverage. Vaccines may also confer additional benefits through reduced infectiousness and mortality in breakthrough cases.

Heterologous vaccine regimen: Stakeholder acceptance and implementation considerations.

Heterologous vaccine regimens deliver antigens through different vaccine components or vector types at sequential time points. Clinical development shows promising results and several candidates may be progressing to licensure in the coming years. This study aimed at exploring future acceptance and uptake of such regimens (also called heterologous prime-boost) and to identify implementation-associated benefits and challenges. Survey tools were developed based on findings from a previous literature search shared with the study team, and exploratory interviews with global stakeholders. An online survey and key informant interviews in six countries were conducted with stakeholders at national and sub-national level, including policy-makers, regulators and implementers. The interview guide and the online survey covered: (a) awareness of, and knowledge about, heterologous vaccine regimens; (b) rating of regimen-associated perceived benefits and challenges; (c) anticipation of possible challenges in relation to four hypothetical introduction scenarios; (d) potential acceptance benefits and challenges at the policy, health facility and recipient level. Sixty-two interviews were conducted at national level. The online survey was completed by 50 participants. Across the four introduction scenarios, respondents considered the highest potential for the introduction of heterologous regimens for immunoprophylaxis was among adolescents/adults for diseases against which no vaccines are currently available. Most reservations were related to logistics, record keeping, and recipient compliance. Adding a new heterologous vaccine regimen to the routine immunization calendar for children was considered feasible if it could generate an increased and longer-term immune response. Introduction in preparation of or following a disease outbreak was considered less favourably, with respondents stressing the difficulty of logistics in emergency situations, and the potential lag in the onset of protection. The recent approval of the first heterologous vaccine regimen for the prevention of Ebola Virus Disease will soon bring new light to the topic.

Impact of prophylactic vaccination strategies on Ebola virus transmission: A modeling analysis.

Ebola epidemics constitute serious public health emergencies. Multiple vaccines are under development to prevent these epidemics and avoid the associated morbidity and mortality. Assessing the potential impact of these vaccines on morbidity and mortality of Ebola is essential for devising prevention strategies. A mean-field compartmental stochastic model was developed for this purpose and validated by simulating the 2014 Sierra Leone epidemic. We assessed the impacts of prophylactic vaccination of healthcare workers (HCW) both alone and in combination with the vaccination of the general population (entire susceptible population other than HCW). The model simulated 8,706 (95% confidence intervals [CI]: 478-21,942) cases and 3,575 (95%CI: 179-9,031) deaths in Sierra Leone, in line with WHO-reported statistics for the 2014 epidemic (8,704 cases and 3,587 deaths). Relative to this base case, the model then estimated that prophylactic vaccination of only 10% of HCW will avert 12% (95% CI: 6%-14%) of overall cases and deaths, while vaccination of 30% of HCW will avert 34% of overall cases (95% CI: 30%-64%) and deaths (95% CI: 30%-65%). Prophylactic vaccination of 1% and 5% of the general population in addition to vaccinating 30% of HCW was estimated to result in reduction in cases by 44% (95% CI: 39%-61%) and 72% (95% CI: 68%-84%) respectively, and deaths by 45% (95% CI: 40%-61%) and 74% (95% CI: 70%-85%) respectively. Prophylactic vaccination of even small proportions of HCW is estimated to significantly reduce incidence of Ebola and associated mortality. The effect is greatly enhanced by the additional vaccination even of small percentages of the general population. These findings could be used to inform the planning of prevention strategies.

Seasonal influenza vaccine dose distribution in 195 countries (2004-2013): Little progress in estimated global vaccination coverage.

Seasonal influenza is an important disease which results in 250,000-500,000 annual deaths worldwide. Global targets for vaccination coverage rates (VCRs) in high-risk groups are at least 75% in adults ≥65 years and increased coverage in other risk groups. The International Federation of Pharmaceutical Manufacturers and Associations Influenza Vaccine Supply (IFPMA IVS) International Task Force developed a survey methodology in 2008, to assess the global distribution of influenza vaccine doses as a proxy for VCRs. This paper updates the previous survey results on absolute numbers of influenza vaccine doses distributed between 2004 and 2013 inclusive, and dose distribution rates per 1000 population, and provides a qualitative assessment of the principal enablers and barriers to seasonal influenza vaccination. The two main findings from the quantitative portion of the survey are the continued negative trend for dose distribution in the EURO region and the perpetuation of appreciable differences in scale of dose distribution between WHO regions, with no observed convergence in the rates of doses distributed per 1000 population over time. The main findings from the qualitative portion of the survey were that actively managing the vaccination program in real-time and ensuring political commitment to vaccination are important enablers of vaccination, whereas insufficient access to vaccination and lack of political commitment to seasonal influenza vaccination programs are likely contributing to vaccination target failures. In all regions of the world, seasonal influenza vaccination is underutilized as a public health tool. The survey provides evidence of lost opportunity to protect populations against potentially serious influenza-associated disease. We call on the national and international public health communities to re-evaluate their political commitment to the prevention of the annual influenza disease burden and to develop a systematic approach to improve vaccine distribution equitably.

Seasonal influenza vaccine dose distribution in 157 countries (2004-2011).

Globally there are an estimated 3-5 million cases of severe influenza illness every year, resulting in 250,000-500,000 deaths. At the World Health Assembly in 2003, World Health Organization (WHO) resolved to increase influenza vaccine coverage rates (VCR) for high-risk groups, particularly focusing on at least 75% of the elderly by 2010. But systematic worldwide data have not been available to assist public health authorities to monitor vaccine uptake and review progress toward vaccination coverage targets. In 2008, the International Federation of Pharmaceutical Manufacturers and Associations Influenza Vaccine Supply task force (IFPMA IVS) developed a survey methodology to assess global influenza vaccine dose distribution. The current survey results represent 2011 data and demonstrate the evolution of the absolute number distributed between 2004 and 2011 inclusive, and the evolution in the per capita doses distributed in 2008-2011. Global distribution of IFPMA IVS member doses increased approximately 86.9% between 2004 and 2011, but only approximately 12.1% between 2008 and 2011. The WHO's regions in Eastern Mediterranean (EMRO), Southeast Asian (SEARO) and Africa (AFRO) together account for about 47% of the global population, but only 3.7% of all IFPMA IVS doses distributed. While distributed doses have globally increased, they have decreased in EURO and EMRO since 2009. Dose distribution can provide a reasonable proxy of vaccine utilization. Based on the dose distribution, we conclude that seasonal influenza VCR in many countries remains well below the WHA's VCR targets and below the recommendations of the Council of the European Union in EURO. Inter- and intra-regional disparities in dose distribution trends call into question the impact of current vaccine recommendations at achieving coverage targets. Additional policy measures, particularly those that influence patients adherence to vaccination programs, such as reimbursement, healthcare provider knowledge, attitudes, practices, and communications, are required for VCR targets to be met and benefit public health.