Intradermal vaccine delivery: will new delivery systems transform vaccine administration?

There has been a recent resurgence of interest in intradermal vaccine delivery. The physiological advantages of intradermal vaccine delivery have been known for some time, but the difficulties associated with performing an intradermal injection have historically limited its use. New delivery systems currently in development facilitate convenient intradermal vaccination, unlocking the potential advantages of this delivery route, and potentially transforming vaccine delivery.     

What can HIV vaccine trials teach us about future HIV vaccine dissemination?

This investigation explored commonalities and differences in barriers and motivators to HIV vaccine trial participation and acceptability of future U.S. Food and Drug Administration (FDA)-approved HIV vaccines in order to identify implications of clinical trials for future HIV vaccine dissemination. Fifteen focus groups were conducted with 157 predominately ethnic minority and low income participants recruited using venue-based sampling in Los Angeles. Data were analyzed using narrative thematic analysis. Barriers and motivators in common across willingness to participate (WTP) in HIV vaccine trials and future HIV vaccine acceptability (e.g., concerns about vaccine-induced infection, false-positives, side effects, efficacy, mistrust and stigma) suggest clinical trials present significant opportunities to develop and evaluate empirically based interventions to support future HIV vaccine dissemination. Barriers specific to HIV vaccine acceptability (e.g., concerns about duration of protection, cross-clade protection, cost and access) also indicate the need for formative research focused specifically on future dissemination. Protection motivation, common to WTP and acceptability, highlights the need to provide and evaluate prevention counseling and education in clinical trials, which may form the basis of evidence-informed preventive interventions to be launched in tandem with dissemination of partial efficacy HIV vaccines.     

Meningococcal vaccine for infants?

With the incidence of meningococcal disease declining in all age groups, ACIP is weighing the need for vaccination in children <2 years.     

Impact of BRICS’ investment in vaccine development on the global vaccine market

Brazil, the Russian Federation, India, China and South Africa – the countries known as BRICS – have made considerable progress in vaccine production, regulation and development over the past 20 years. In 1993, all five countries were producing vaccines but the processes used were outdated and non-standardized, there was little relevant research and there was negligible international recognition of the products. By 2014, all five countries had strong initiatives for the development of vaccine technology and had greatly improved their national regulatory capacity. South Africa was then the only BRICS country that was not completely producing vaccines. South Africa is now in the process of re-establishing its own vaccine production and passing beyond the stage of simply importing, formulating and filling vaccine bulks. Changes in the public sector’s price per dose of selected vaccines, the global market share represented by products from specific manufacturers, and the attractiveness, for multinational companies, of partnership and investment opportunities in BRICS companies have all been analysed. The results indicate that the BRICS countries have had a major impact on vaccine price and availability, with much of that impact attributable to the output of Indian vaccine manufacturers. China is expected to have a greater impact soon, given the anticipated development of Chinese vaccine manufacturers in the near future. BRICS’ accomplishments in the field of vaccine development are expected to reshape the global vaccine market and accelerate access to vaccines in the developing world. The challenge is to turn these expectations into strategic actions and practical outcomes.     

Effectiveness of inactivated influenza vaccine in children by vaccine dose, 2013–18

ObjectivesWe assessed the vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) by vaccine dose in children aged 6 months to 12 years for whom two doses are recommended in Japan to ascertain the appropriate vaccine doses.MethodsVE was assessed according to a test-negative case-control design based on rapid influenza diagnostic test (RIDT) results. Children aged 6 months to 12 years with a fever ≥38 °C who had received an RIDT in outpatient clinics of 24 hospitals were enrolled for all five seasons since 2013/14. VE by vaccine dose (none vs. once or twice, and once vs. twice) was analyzed.ResultsIn the dose analysis, 20,033 children were enrolled. Both one- and two-dose regimens significantly reduced cases in preventing any influenza, influenza A, and influenza B, but there was no significant difference in adjusted VE between one- and two-dose regimens overall (adjusted OR, 0.560 [95% CI, 0.505–0.621], 0.550 [95% CI, 0.516–0.586]), 0.549 [95% CI, 0.517–0.583], and 1.014 [95% CI, 0.907–1.135], for none vs. once, none vs. twice, none vs. once or twice, and once vs. twice for any influenza, respectively). Both one- and two-dose regimens significantly reduced cases with any influenza and influenza A every season. Also, both regimens significantly reduced cases of any influenza, influenza A, and influenza B among children aged 1–12 years, especially among those aged 1–5 years. In the 2013/14, 2015/16, and 2016/17 seasons, however, only the two-dose regimen was significantly effective in preventing influenza B. Both one- and two-dose regimens significantly reduced cases involving hospitalization due to any influenza and influenza A.ConclusionsBoth one- and two-doses regimens of IIV were effective in preventing influenza for children aged 6 months to 12 years. The two-dose regimen was more effective against influenza B in some seasons.     

Is a rhinovirus vaccine possible?

Renewal of support for efforts to develop a rhinovirus vaccine seems justified in the light of newer epidemiologic and immunologic studies. The major contribution of RV to acute upper respiratory disease in all age groups but especially in young children emphasizes the public health importance of an effective vaccine. Epidemiologic surveillance of RV infections in widely separated areas has identified two relevant phenomena. First, in each area, certain serotypes were more frequently encountered and tended to persist. Such "common" serotypes accounted for a disproportionate share of the infections recognized and, hence, constitute special targets for immunization. Second, a clear increase over time in the proportion of RV isolates representing higher numbered (types 56-89) serotypes or untypable strains (potentially new serotypes) suggests that new serotypes continue to emerge as the result of progressive antigenic shift. The common origin of the multitudinous RV serotypes so suggested is consistent with the extensive antigenic cross-relations which are becoming evident. Systematic cross-testing with monospecific antisera, especially when high titer sera are employed, has revealed an appreciable number of one-way and reciprocal relations. Largely fortuitous observations of naturally or experimentally infected humans have revealed many additional cross-relations manifested by concurrent response to heterologous RV and presumably attributable to sensitizations resulting from prior RV infections. A model for this has been provided by rabbits immunized sequentially with different potent RV immunogens. Available information as displayed in figure 2 indicates that extensive cross-relations do exist and that sizeable groups of closely related serotypes may be identified. More intensive search for heterotypic response to infection of man coupled with selective use of the rabbit model should define the full extent and strength of cross-relations and identify completely the more closely related groups of serotypes as the basis for formulation of a broadly effective RV vaccine containing a limited number of serotypes. The cross-relations described are based entirely on development of serum neutralizing antibody, the presence of which in man is clearly correlated with relative protection against infection and disease. While this protection may well prove to be mediated largely by concomitant nasal secretory antibody, it is not unreasonable to expect that the antigenic cross-relations also would be manifested in secretory antibody response. These important questions concerning secretory antibody can be best explored in a limited series of volunteer trials with selected cross-related RV serotypes in which homotypic and heterotypic protection could be correlated with serum and nasal secretory antibody. The state of current knowledge, as I view it, is sufficient to justify initiation of such trials at any time.     

Early smallpox vaccine manufacturing in the United States: Introduction of the “animal vaccine” in 1870, establishment of “vaccine farms”, and the beginnings of the vaccine industry

For the first 80–90 years after Jenner’s discovery of vaccination in 1796, the main strategy used to disseminate and maintain the smallpox vaccine was arm-to-arm vaccination, also known as Jennerian or humanized vaccination. A major advance occurred after 1860 with the development of what was known as “animal vaccine”, which referred to growing vaccine material from serial propagation in calves before use in humans. The use of “animal vaccine” had several advantages over arm-to-arm vaccination: it would not transmit syphilis or other human diseases, it ensured a supply of vaccine even in the absence of the spontaneous occurrence of cases of cowpox or horsepox, and it allowed the production of large amounts of vaccine. The “animal vaccine” concept was introduced in the United States in 1870 by Henry Austin Martin. Very rapidly a number of “vaccine farms” were established in the U.S. and produced large quantities of “animal vaccine”. These “vaccine farms” were mostly established by medical doctors who saw an opportunity to respond to an increasing demand of smallpox vaccine from individuals and from health authorities, and to make a profit. The “vaccine farms” evolved from producing only smallpox “animal vaccine” to manufacturing several other biologics, including diphtheria- and other antitoxins. Two major incidents of tetanus contamination happened in 1901, which led to the promulgation of the Biologics Control Act of 1902. The US Secretary of the Treasury issued licenses to produce and sell biologicals, mainly vaccines and antitoxins. Through several mergers and acquisitions, the initial biologics licensees eventually evolved into some of the current major American industrial vaccine companies. An important aspect that was never clarified was the source of the vaccine stocks used to manufacture the smallpox “animal vaccines”. Most likely, different smallpox vaccine stocks were repeatedly introduced from Europe, resulting in polyclonal vaccines that are now recognized as “variants” more appropriately than “strains”. Further, clonal analysis of modern “animal vaccines” indicate that they are probably derived from complex recombinational events between different strains of vaccinia and horsepox. Modern sequencing technologies are now been used by us to study old smallpox vaccine specimens in an effort to better understand the origin and evolution of the vaccines that were used to eradicate the smallpox.     

Can the vaccine adverse event reporting system be used to increase vaccine acceptance and trust?

Vaccine refusal has an impact on public health, and the human pappillomavirus (HPV) vaccine is particularly underutilized. Research suggests that it may be difficult to change vaccine-related attitudes, and there is currently no good evidence to recommend any particular intervention strategy. One reason for vaccine hesitancy is lack of trust that vaccine harms are adequately documented and reported, yet few communication strategies have explicitly attempted to improve this trust. This study tested the possibility that data from the vaccine adverse event reporting system (VAERS) can be used to increase trust that vaccine harms are adequately researched and that potential harms are disclosed to the public, and thereby improve perceptions of vaccines. In the study, participants were randomly assigned to one of three communication interventions. All participants read the Centers for Disease Control (CDC) vaccine information statement (VIS) for the HPV vaccine. Two other groups were exposed to additional information about VAERS, either summary data or full detailed reports of serious adverse events from 2013. Results showed that the CDC's VIS alone significantly increased perceptions of vaccine benefits and decreased perceived risks. Participants who were also educated about VAERS and given summary data about the serious adverse events displayed more trust in the CDC and greater HPV vaccine acceptance relative to the VIS alone. However, exposure to the detailed VAERS reports significantly reduced trust in the CDC and vaccine acceptance. Hence, general information about the VAERS data slightly increased trust in the CDC and improved vaccine acceptance, but the specific VAERS reports negatively influenced both trust and acceptance. Implications for communicating about vaccines are discussed.     

Is vaccine hesitancy justified? Benchmarking post-market vaccine risks with five commonly used medicinal products in Canada

ObjectiveAlthough vaccines are one of the most cost-effective, low-risk healthcare approaches that save thousands of lives every year, paradoxical fear about vaccine safety is a major roadblock for achieving widespread vaccination coverage. The objective of this study is to change public perception of vaccine safety by presenting real-world incidence of adverse events following immunization (AEFIs).MethodsIn this study, we used Canadian post-market adverse events data to estimate the real-world risk of AEFI and benchmarked them against five commonly used drug types—ACE inhibitors, beta2 adrenergic receptors, penicillins, proton pump inhibitors, and HMG-CoA reductase inhibitors.ResultsOur analysis shows that post-market AEFIs are rare, and vaccination generally carries a significantly lower risk compared to some commonly used medicinal product types.ConclusionDespite some limitations with using post-trial adverse events data, we believe that the evidence presented in this study, especially the comparative risk analysis between vaccines and medicinal products, when communicated through proper channels, can help vaccine-hesitant individuals overcome their perceived safety concerns with regard to vaccines.     

Safety and immunogenicity of pneumococcal protein vaccine candidates: Monovalent choline-binding protein A (PcpA) vaccine and bivalent PcpA–pneumococcal histidine triad protein D vaccine

Background

Pneumococcal vaccines based on protein antigens may provide expanded protection against Streptococcus pneumoniae.

Objective

To evaluate safety and immunogenicity in adults of pneumococcal vaccine candidates comprising S. pneumoniae pneumococcal histidine triad protein D (PhtD) and pneumococcal choline-binding protein A (PcpA) in monovalent and bivalent formulations.

Methods

This was a phase I, randomized, observer-blinded, placebo-controlled, step-wise dose-escalation study. Following a pilot safety study in which participants received one intramuscular injection of either aluminum hydroxide (AH)–adjuvanted PcpA (25 μg) or PhtD–PcpA (10 μg each), participants in the main study received AH–adjuvanted PcpA (25 μg), AH–adjuvanted PhtD–PcpA (10, 25, or 50 μg each), unadjuvanted PhtD–PcpA (25 μg each), or placebo as 2 injections 30 days apart. Assignment of successive dose cohorts was made after blinded safety reviews after each dose level. Safety endpoints included rates of solicited injection site and systemic reactions, unsolicited adverse events (AEs), serious AEs (SAEs), and safety laboratory tests. Immunogenicity endpoints included levels of anti-PhtD and anti-PcpA antibodies (ELISA).

Results

Six adults 18–50 years of age were included in the pilot study and 125 in the main study. No obvious increases in solicited reactions or unsolicited AEs were reported with escalating doses (adjuvanted vaccine) after either injection, or with repeated administration. Adjuvanted vaccine candidates were associated with a higher incidence of solicited reactions (particularly injection site reactions) than unadjuvanted vaccine candidates. However, no SAE or discontinuation due to an AE occurred. Geometric mean concentrations of anti-PhtD IgG and anti-PcpA IgG increased significantly after injection 2 compared with injection 1 at each dose level. No enhancement of immune responses was shown with adjuvanted vaccine candidates compared with the unadjuvanted vaccine candidate. In the dose-escalating comparison, a plateau effect at the 25 μg dose was observed as measured by geometric mean concentrations and by fold increases.

Conclusions

Promising safety profiles and immunogenicity of these monovalent and bivalent protein vaccine candidates were demonstrated in an adult population (ClinicalTrials.gov registry no. NCT01444339).     

The influence of parents’ information processing on childhood vaccine acceptance after a vaccine crisis in China

Drawing upon the protective action decision model and the heuristic-systematic model, this study investigated the determinants of parents’ response to the 2016 vaccine crisis in Shandong Province, China. A survey was conducted from Anhui Province (N = 456). The findings showed that both perceived vaccine knowledge and perceptions of risk from the vaccine crisis were vital in predicting parents’ information insufficiency (the perceived discrepancy between actual and desired levels of vaccine knowledge), information seeking, information processing (where parents make a judgement about information validity), and their intentions towards childhood vaccination. In addition, information insufficiency and information seeking also significantly facilitated parents’ information processing. When parents described processing information systematically, they were more likely to accept childhood vaccination. On the other hand, seeking more information about the crisis did not influence reported childhood vaccination practices. Implications and suggestions for health-related crisis communication research are discussed.     

Does a major change to a COVID-19 vaccine program alter vaccine intention? A qualitative investigation

BackgroundOn 8th April 2021, the Australian Technical Advisory Group on Immunisation (ATAGI) made the Pfizer-BioNtech (Comirnaty) vaccine the “preferred” vaccine for adults in Australia aged < 50 years due to a risk of thrombosis with thrombocytopenia syndrome (TTS) following AstraZeneca vaccination. We sought to understand whether this impacted COVID-19 vaccine intentions.MethodWe undertook qualitative interviews from February – April 2021 before and after the program change with 28 adults in Perth, Western Australia. Using our COVID-19 vaccine intentions model, we assessed changes in participants’ COVID-19 vaccine intention before and after the program change. Participants were classified as 1) ‘acceptors’: no concerns about COVID-19 vaccine safety, efficacy, access and would accept whatever vaccine is offered, 2) ‘cautious acceptors’: some concerns and would prefer a particular vaccine brand but would accept whatever is offered, 3) ‘Wait awhile’: for more data, easier access, for another vaccine brand, a greater perceived COVID-19 threat or until mandatory, or 4) ‘refuser’: no intention to vaccinate due to concerns about safety and/or efficacy.ResultsBefore the change, 7/18 of those aged < 50 years were ‘acceptors,’ 10/18 were ‘cautious acceptors’ and 1/18 was ‘wait awhile.’ Overall, 14/18 participants had the same COVID-19 vaccine intention after the change; 4/18 became more concerned. For those aged ≥ 50 years and before the change, 5/10 were ‘acceptors’ and 5/10 were ‘cautious acceptors.’ After the change, 8/10 still had the same COVID-19 vaccine intention; 2/10 became more cautious. The major concern before the program change was COVID-19 vaccines having different vaccine efficacy; the concern pivoted to safety.ConclusionThe majority of participants were ‘cautious acceptors’ who intended on being vaccinated; many had this intention before and after the program change. The Australian government, health care providers and media need to better address COVID-19 vaccine concerns to assist those with COVID-19 vaccine intentions receive a vaccine.     

A social vaccine? Social and structural contexts of HIV vaccine acceptability among most-at-risk populations in Thailand

Abstract

A safe and efficacious preventive HIV vaccine would be a tremendous asset for low- and middle-income country (LMIC) settings, which bear the greatest global impact of AIDS. Nevertheless, substantial gaps between clinical trial efficacy and real-world effectiveness of already licensed vaccines demonstrate that availability does not guarantee uptake. In order to advance an implementation science of HIV vaccines centred on LMIC settings, we explored sociocultural and structural contexts of HIV vaccine acceptability among most-at-risk populations in Thailand, the site of the largest HIV vaccine trial ever conducted. Cross-cutting challenges for HIV vaccine uptake – social stigma, discrimination in healthcare settings and out-of-pocket vaccine cost – emerged in addition to population-specific barriers and opportunities. A ‘social vaccine’ describes broad sociocultural and structural interventions – culturally relevant vaccine promotion galvanised by communitarian norms, mitigating anti-gay, anti-injecting drug user and HIV-related stigma, combating discrimination in healthcare, decriminalising adult sex work and injecting drug use and providing vaccine cost subsidies – that create an enabling environment for HIV vaccine uptake among most-at-risk populations. By approaching culturally relevant social and structural interventions as integral mechanisms to the success of new HIV prevention technologies, biomedical advances may be leveraged in renewed opportunities to promote and optimise combination prevention.