by Charlotte Kilpatrick | Sep 6, 2024 | Global Health |
WHO announced in September 2024 that the first phase of a polio vaccination campaign has been “successfully” completed in Gaza. Over 187,000 children under ten years were vaccinated with novel oral polio vaccine type 2 (nOPV2) in central Gaza between 1st and 3rd September. Coverage for this phase has exceeded the initial estimated target of 157,000 children, which WHO attributes to population movement towards central Gaza and expanded coverage in areas outside the humanitarian pause zone. Vaccination will continue at four large health facilities in central Gaza to ensure that no child is missed in the area.
First phase complete
The first phase was conducted by 513 teams, comprising more than 2180 health and community outreach workers. Vaccinations were offered at 143 fixed sites, including hospitals, medical points, primary care centres, camps where displaced people are living, key public gathering spaces, food and water distribution points, and transit routes. Mobile teams also visited tents and hard-to-reach areas to ensure families who were unable to attend fixed sites were able to access vaccines. Special missions to Al-Maghazi, Al-Bureij, and Al-Mussader were also needed to reach a “substantial number of children” who were eligible for vaccination but unable to reach vaccination sites.
Dr Richard Peeperkorn, WHO Representative for the occupied Palestinian territory described the completed first phase as “positive momentum”.
“It has been extremely encouraging to see thousands of children being able to access polio vaccines, with the support of their resilient families and courageous health workers, despite the deplorable conditions they have braved over the last 11 months.”
The next phases
The next phase of the campaign will be conducted in southern Gaza between 5th and 8th September, targeting an estimated 340,000 children under ten. This phase will involve 517 teams, including 384 mobile teams. Almost 300 community outreach workers have begun outreach to families in southern Gaza to raise awareness about the campaign. 490 vaccine carriers, 90 cold storage boxes, and additional supplies have been transferred to Khan Younis for distribution. The third and final phase of the campaign will be implemented in northern Gaza between 9th and 11th September, targeting around 150,000 children.
Dr Peeperkorn commented that the “successful delivery” of the first phase is a “culmination of immense coordination among various partners” and donors. It “underscores the importance of peace for the health and well-being of people in Gaza”.
“We call on all parties to continue fulfilling their commitment to the humanitarian pauses as the second phase of the campaign begins tomorrow.”
Each round of the campaign must achieve vaccine coverage of 90% of higher to stop the polio outbreak and reduce the risk of re-emergence “given the severely disrupted health, water, and sanitation systems in the Gaza Strip”. Coverage will be monitored throughout the campaign with the potential to extend vaccinations if needed to meet coverage targets.
For insights into developing effective vaccination strategies in emergency and routine situations do join us at the Congress in Barcelona this October and subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Aug 19, 2024 | Technology |
In August 2024 Tonix Pharmaceuticals “reiterated its commitment” to advancing the development of its live attenuated virus vaccine TNX-801 for the prevention of mpox and other infectious diseases. This comes after WHO declared that the spread of mpox in Africa represents a public health emergency of international concern. TNX-801 is a live replicating attenuated vaccine candidate, based on horsepox, and is believed to provide protection with “better tolerability” than 20th century vaccinia viruses.
TNX-801
The platform behind TNX-801 was chosen by US NIH for Project NextGen efforts against SARS-CoV-2 but has also protected animals against lethal challenge with intratracheal Clade 1 monkeypox virus. Tonix states that the recombinant horsepox virus vaccine uses a live replicating, attenuated virus that has “been shown to be >1,000-fold more attenuated than 20th century vaccinia” (VACV) strains in immunocompromised mice. The virus can be engineered to express foreign genes and is a strong platform for vaccine development because they have:
- Large packaging capacity for exogenous DNA inserts
- Precise virus-specific control of exogenous gene insert expression
- Lack of persistence or genomic integration in the host
- Strong immunogenicity as a vaccine
- The ability to rapidly generate vector/insert constructs
- Potential to be readily manufacturable at scale
- The ability to provide direct antigen presentation
Although Tonix’s current formulation is a frozen liquid, the team indicates that future lyophilised versions could be stored and shipped at standard refrigeration.
“Horsepox-based vaccines are designed to be single dose, vial-sparing vaccines that can be administered without sterile injection, manufactured using conventional cell culture systems with the potential for mass scale production, and packaged in multi-dose vials.”
A need for accelerated efforts
Dr Seth Lederman, Chief Executive Officer of Tonix, recognises that the WHO declaration “underscores the urgent need for additional treatments to stop these outbreaks and save lives”.
“We are motivated to advance development for our mpox vaccine with urgency given the global public health emergency.”
Dr Lederman states that TNX-801 “combines immune protection with improved tolerability and safety” and has the advantage of a single dose administration.
“Also, the stability of live virus vaccines eliminates the need for ultra-cold storage which complicates the widespread use of mRNA vaccines in Africa, where they are needed most right now.”
We look forward to hearing more about Tonix’s mpox vaccine development at the Congress in Barcelona this October. To join us get your tickets here, and don’t forget to subscribe to our weekly newsletters for vaccine updates.
by Charlotte Kilpatrick | Mar 11, 2024 | Technology |
In March 2024 CEPI announced that it is providing up to $1.9 million to Ghent University to support investigations into a “pioneering vaccine stabilisation technique” that could end the need for frozen storage of mRNA vaccines and support faster responses within the 100 Days Mission. The University will test the preclinical performance of optimised mRNA vaccines using a specialised Galsomes platform after “spin-freezing”. This approach has been pioneered by a spin-off from Ghent University, RheaVita.
A novel approach
CEPI states that the process of freeze-drying dehydrates and stores vaccines and other products as powder at heat-stable temperatures to “inhibit spoilage, extend shelf life, and increase access” particularly in settings that are remote or lower-resource. Spin-freezing is a technique that works by “rapidly rotating” vials of vaccine along an axis while the flow of an inert and cold gas solidifies the vaccine into a “thin powder film” around the side of the vial.
“This allows for a much faster drying process and offers manufacturers more control of the process, which can help improve the quality of vaccines being produced.”
Vaccines can also be frozen continuously, vial by vial, which reduces the risk of “expensive and time-consuming bottlenecks and delays”, which often occur during traditional freeze-drying when vaccines are manufactured in batches. Although batch manufacturing “has long been the industry standard”, CEPI suggests that continuous manufacturing could bring “improved efficiency”, with raw materials “constantly fed into the production line” to bring more vaccines to market at a faster rate. Furthermore, this approach could reduce labour and waste, bringing cost benefits.
Flipping the process
Ingrid Kromann, Acting Executive Director of Vaccine Manufacturing and Supply Chain at CEPI, commented that “investors are increasingly looking to meet the challenge of rapidly scaling up thermostable mRNA vaccine doses” to ensure “wider global delivery”.
“In addition to making mRNA vaccines thermostable, spin-freezing has the potential to flip the usual batch production process utilised by pharmaceutical manufacturers and instead offer continuous manufacturing, which, if successful, could promote fast and flexible mRNA vaccine production in response to future outbreaks.”
From Ghent University Dr Ine Lentacker and Professor Thomas De Beer are “excited” by the collaboration, which provides them with “a great opportunity to improve the thermostability” of mRNA Galsomes.
“We believe that our efforts to address challenges posed by cold chain distribution could significantly contribute to equitable access to mRNA vaccines globally.”
We’re looking forward to hearing more from representatives of CEPI with insights into how the organisation is encouraging innovation and accelerating pandemic preparedness at the Congress in Washington this April. Do get your tickets to join us at this link and don’t forget to subscribe to our newsletters here.
by Charlotte Kilpatrick | Mar 4, 2024 | Technology |
A study published in Vaccine X in February 2024 presents an evaluation of freeze prevention of vaccines transported and stored in the WHO-prequalified freeze-preventive cold box (FPCB) in comparison with the current standard cold boxes (SCBs). The evaluation was conducted across five health facilitates in Nepal. The authors find several advantages to the FPCB but suggest that smaller and lighter models would be more appropriate for Nepal’s immunisation needs and similar immunisation programmes globally.
Transportation and storage
“Vaccines lose potency over time, and this loss is temperature dependent.”
The study highlights WHO guidelines for vaccine handling, which recommend “specific storage conditions” to “ensure quality is maintained throughout the vaccine life cycle”. Interestingly, while vaccine vial monitors to identify exposure to heat have been “available for decades”, there are no vial-level indicators for freezing.
Freezing is a particular concern for liquid vaccines with aluminium salt adjuvants, which have increased freeze sensitivity: “freezing can irreversibly damage these vaccines, reducing potency and compromising protective immunogenicity in recipients”.
“The importance of protecting vaccines from freezing will become even more pressing globally as introductions of new vaccines put pressure on already weak vaccine supply chain systems.”
The authors state that, in Nepal, cold boxes are “primarily used” to transport vaccines from “higher cold chain points to health posts”. Vaccine freezing can cause closed-vial vaccine wastage, with “financial implications for immunisation programmes”, or in cases where it goes undetected, can lead to “loss of vaccine potency and efficacy”.
“Freeze prevention at the equipment level mitigates these risks and eliminates the need for shake testing or vial-level freeze indicators, which have not yet proven cost-effective nor been implemented comprehensively.”
SBCs vs FPCBs in Nepal
The study presents the “first real-world evaluation” of a WHO Performance, Quality, and Safety (PQS)-prequalified freeze-preventative cold box (FPCB). Cold boxes have a greater capacity than vaccine carriers and transport vaccines between different levels of the supply chain. This increased capacity means that more vaccines are transported, which therefore presents a greater financial loss if the vaccines freeze.
Qingdao Leff International Trading Company was the first manufacturer to receive WHO PQS prequalification for an FPCB in 2020. The technology comprises a barrier liner between the ice packs and vaccine storage area to prevent direct contact of vials with ice packs.
The Himalayan terrain reportedly poses “major geographical challenges for vaccine distribution, transportation, and storage”. After a shift from a “highly centralised” system to a more decentralised model in 2015, Nepal has faced “both structural and operational issues”, from infrastructural weakness and shortage of skilled staff to delays and lack of coordination. Vaccination coverage “varies considerably across its diverse and geographically dispersed population”.
In response, Nepal has dedicated “significant resources” to improve the service delivery infrastructure of its national immunisation programme”. The authors comment that reaching underserved and widely dispersed populations will “boost vaccine coverage”.
Vaccines in Nepal are “typically” collected and distributed from regional and district cold chain points to health posts once a month for routine immunisations. Further trips are required for vaccination campaigns. Vaccines are transported by the alternate vaccine delivery (AVD) system or health workers. The former involves “local persons engaged in this activity on a part-time basis”, who use cold boxes or carriers in their own vehicles.
Performing to standards
The authors reflect that the primary purpose of the equipment is to prevent vaccines from freezing; in terms of this purpose the FPCB “performed to standards”. The SCBs cooled down “much more quickly” than the FPCBs, thanks to the thermal buffering. While this is “not much of an issue” for extended journeys or temporary storage, the slower cooldown can mean “exposure to elevated temperatures for most of the session” in short outreach sessions. Although the amount and level of thermal exposure is “relatively minimal”, it can be “very noticeable” for health workers trained to keep vaccines within the “acceptable” range: above 0 °C and below + 10 °C.
Additionally, the authors identified a “relatively long period of freezing” in SCBs, which is “not uncommon and can lead to loss of vaccine potency”. Despite “numerous high temperature excursions”, there was no reported incidence of vaccine wastage due to total heat exposure.
“The primary advantage of FPCBs over SCBs is prevention of freezing even when fully frozen, non-conditioned ice packs are used.”
This advantage is expected to “simplify logistics” because if health workers can use fully frozen ice packs, they will need less time to prepare cold boxes. A potential further advantage is a “reduced training burden”. The authors recommend further research and development in pursuit of “smaller and lighter FPCBs relative to their usable storage volume”. Furthermore, investing in FPCBs to prevent the freezing of expensive vaccine shipments would “potentially” be good value as the cost of procuring one FPCB is “much less” than the value of the vaccines that are prevented from freezing.
The paper concludes with recommendations for future research and development, including:
- Explicitly modelling, validating in real-world conditions, and publishing estimated vaccine degradation due to any additional heat exposure from demonstrated longer cooldown periods
- Further product development that might lead to lighter equipment with more storage space and a shorter cooldown period while still thermally protecting vaccine potency from both freezing and heat exposure
Did you read the paper? What useful contributions does it make to vaccine technology discourse? How might the FPCBs fare in your vaccination programmes? For more on novel vaccine technologies and strategies don’t forget to join us in Washington this April for the Congress or subscribe to our newsletters here.
