Global VAX: A U.S. contribution to global COVID-19 vaccination efforts, 2021-2023.

In December 2021 the U.S. Government announced a new, whole-of-government $1.8 billion effort, the Initiative for Global Vaccine Access (Global VAX) in response to the global COVID-19 pandemic. Using the foundation of decades of U.S. government investments in global health and working in close partnership with local governments and key global and multilateral organizations, Global VAX enabled the rapid acceleration of the global COVID-19 vaccine rollout in selected countries, contributing to increased COVID-19 vaccine coverage in some of the world's most vulnerable communities. Through Global VAX, the U.S. Government has supported 125 countries to scale up COVID-19 vaccine delivery and administration while strengthening primary health care systems to respond to future health crises. The progress made by Global VAX has paved the way for a stronger global recovery and improved global health security.

Barriers and activities to implementing or expanding influenza vaccination programs in low- and middle-income countries: A global survey.

INTRODUCTION: Despite considerable global burden of influenza, few low- and middle-income countries (LMICs) have national influenza vaccination programs. This report provides a systematic assessment of barriers to and activities that support initiating or expanding influenza vaccination programs from the perspective of in-country public health officials. METHODS: Public health officials in LMICs were sent a web-based survey to provide information on barriers and activities to initiating, expanding, or maintaining national influenza vaccination programs. The survey primarily included Likert-scale questions asking respondents to rank barriers and activities in five categories. RESULTS: Of 109 eligible countries, 62% participated. Barriers to influenza vaccination programs included lack of data on cost-effectiveness of influenza vaccination programs (87%) and on influenza disease burden (84%), competing health priorities (80%), lack of public perceived risk from influenza (79%), need for better risk communication tools (77%), lack of financial support for influenza vaccine programs (75%), a requirement to use only WHO-prequalified vaccines (62%), and young children require two vaccine doses (60%). Activities for advancing influenza vaccination programs included educating healthcare workers (97%) and decision-makers (91%) on the benefits of influenza vaccination, better estimates of influenza disease burden (91%) and cost of influenza vaccination programs (89%), simplifying vaccine introduction by focusing on selected high-risk groups (82%), developing tools to prioritize target populations (80%), improving availability of influenza diagnostic testing (79%), and developing collaborations with neighboring countries for vaccine procurement (74%) and regulatory approval (73%). Responses varied by country region and income status. CONCLUSIONS: Local governments and key international stakeholders can use the results of this survey to improve influenza vaccination programs in LMICs, which is a critical component of global pandemic preparedness for influenza and other pathogens such as coronaviruses. Additionally, strategies to improve global influenza vaccination coverage should be tailored to country income level and geographic location.

The partnership for influenza vaccine introduction (PIVI): Supporting influenza vaccine program development in low and middle-income countries through public-private partnerships.

Influenza vaccination remains the most effective tool for reducing seasonal influenza disease burden. Few Low and Middle-Income Countries (LMICs) have robust, sustainable annual influenza national vaccination programs. The Partnership for Influenza Vaccine Introduction (PIVI) was developed as a public-private partnership to support LMICs to develop and sustain national vaccination programs through time-limited vaccine donations and technical support. We review the first 5 years of experience with PIVI, including the concept, country progress toward sustainability, and lesson learned. Between 2013 and 2018, PIVI worked with Ministries of Health in 17 countries. Eight countries have received donated vaccines and technical support; of these, two have transitioned to sustained national support of influenza vaccination and six are increasing national support of the vaccine programs towards full transition to local vaccine program support by 2023. Nine additional countries have received technical support for building the evidence base for national policy development and/or program evaluation. PIVI has resulted in increased use of vaccines in partner countries, and early countries have demonstrated progress towards sustainability, suggesting that a model of vaccine and technical support can work in LMICs. PIVI expects to add new country partners as current countries transition to self-reliance.

Accelerated pharmaceutical protein development with integrated cell free expression, purification, and bioconjugation.

The use of living cells for the synthesis of pharmaceutical proteins, though state-of-the-art, is hindered by its lengthy process comprising of many steps that may affect the protein's stability and activity. We aimed to integrate protein expression, purification, and bioconjugation in small volumes coupled with cell free protein synthesis for the target protein, ciliary neurotrophic factor. Split-intein mediated capture by use of capture peptides onto a solid surface was efficient at 89-93%. Proof-of-principle of light triggered release was compared to affinity chromatography (His6 fusion tag coupled with Ni-NTA). The latter was more efficient, but more time consuming. Light triggered release was clearly demonstrated. Moreover, we transferred biotin from the capture peptide to the target protein without further purification steps. Finally, the target protein was released in a buffer-volume and composition of our choice, omitting the need for protein concentration or changing the buffer. Split-intein mediated capture, protein trans splicing followed by light triggered release, and bioconjugation for proteins synthesized in cell free systems might be performed in an integrated workflow resulting in the fast production of the target protein.

Pharmacokinetic aspects of retinal drug delivery.

Drug delivery to the posterior eye segment is an important challenge in ophthalmology, because many diseases affect the retina and choroid leading to impaired vision or blindness. Currently, intravitreal injections are the method of choice to administer drugs to the retina, but this approach is applicable only in selected cases (e.g. anti-VEGF antibodies and soluble receptors). There are two basic approaches that can be adopted to improve retinal drug delivery: prolonged and/or retina targeted delivery of intravitreal drugs and use of other routes of drug administration, such as periocular, suprachoroidal, sub-retinal, systemic, or topical. Properties of the administration route, drug and delivery system determine the efficacy and safety of these approaches. Pharmacokinetic and pharmacodynamic factors determine the required dosing rates and doses that are needed for drug action. In addition, tolerability factors limit the use of many materials in ocular drug delivery. This review article provides a critical discussion of retinal drug delivery, particularly from the pharmacokinetic point of view. This article does not include an extensive review of drug delivery technologies, because they have already been reviewed several times recently. Instead, we aim to provide a systematic and quantitative view on the pharmacokinetic factors in drug delivery to the posterior eye segment. This review is based on the literature and unpublished data from the authors' laboratory.

Does habituation to humans influence predator discrimination in Gunther's dik-diks (Madoqua guentheri)?

Animals living around humans may habituate to us, but little is known about the consequences of this habituation. Some wildlife managers assume that habituation to humans makes individuals less likely to respond to natural predators, which is something to be avoided in captive breeding programmes where animals are destined for release. We conducted a playback experiment where we broadcast the sounds of a terrestrial predator and the song from a non-threatening bird to Gunther's dik-diks (Madoqua guentheri), a small ungulate that is vulnerable to many predators, in areas where dik-diks were and were not habituated to humans. Contrary to our expectation, habituated dik-diks discriminated the predator sounds from the birdsong, while unhabituated dik-diks failed to make this discrimination. Our results demonstrate that humans may influence predation hazard assessment, but we should not generally assume that human-habituated animals will be especially vulnerable to predators.