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      COVID-19 vaccine inequity, dependency, and production capability in low-income and middle-income countries: the case of Bangladesh

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          Abstract

          Bangladesh is listed among the 57 human resource for health (HRH) crisis countries as identified by the Global Health Workforce Alliance.1, 2 Despite shortages and maldistribution of health-care personnel, Bangladesh was known for successful immunisation campaigns even before the COVID-19 pandemic. 3 The COVID-19 vaccination drive initially was not smooth for Bangladesh, but the country has, since July 2021, regained its reputation for strong vaccination efforts. COVID-19 vaccination started on Feb 7, 2021, with the ChAdOx1-nCoV-19 vaccine known as Covishield, (Serum Institute India [SII]). Vaccination was initially postponed while the SII suspended the export of vaccines as the number of COVID-19 infections in India increased. The Government of Bangladesh, however, managed to procure vaccines from alternative sources, which helped to alleviate its dependency on a single source. The Government intends to administer four different vaccines (Covishield, BBIBP-CorV [Sinopharm], Comirnaty [Pfizer-BioNTech], and Spikevax [Moderna]) to 170 million people in Bangladesh. As of December 13, 2021, Bangladesh has administered 86·5 million first doses and 43·3 million second doses (figure ), 4 equating to roughly 50% of the total Bangladeshi population having received at least one dose and roughly 25% having been administered two doses of COVID-19 vaccines. Despite vaccine hesitancy and commonly held misconceptions about vaccines globally, vaccine acceptance among this population is encouraging. Like other low-income and middle-income countries (LMIC), Bangladesh has been supported by COVAX, which is co-led by the Coalition for Epidemic Preparedness Innovations, Gavi, the Vaccine Alliance, WHO, and UNICEF to ensure equitable access to COVID-19 vaccines. After Indonesia, COVAX vaccine roll-out in Bangladesh ranks second highest among southeast Asian countries. This achievement is a monumental feat for Bangladesh given that high-income countries have already administered 69 times more doses than Bangladesh, showing a stratified and inequitable vaccine procurement and roll-out. 5 Figure COVID-19 vaccination profile in Bangladesh as of December 13, 2021 Tedros Adhanom Ghebreyesus, Director-General of WHO, notes that inequitable global distribution of the COVID-19 vaccine will burden LMICs most, resulting in a catastrophic moral failure. 6 The possibility of this moral failure accentuates the importance of sharing technologies among manufacturers to enhance the capacity of vaccine manufacturing facilities in LMICs, which could then allow vaccines to be manufactured locally and complement global efforts to ensure equitable COVID-19 vaccine supply. Both Bangladeshi Prime Minister Sheikh Hasina and Muhammad Yunus, the only Nobel Laureate in Peace (2006) from Bangladesh, have been instrumental in a campaign to declare COVID-19 vaccines a global common good. This endeavour is a joint appeal from 3000 people including international personalities, Nobel Laureates, global leaders, international organisations, pharmaceutical companies, and governments. 7 In addition to procuring vaccines from a diverse portfolio of manufacturers, Bangladesh has adopted a model to become self-reliant in vaccine manufacturing. A Bangladeshi biotech company, Globe Biotech, has completed non-human primate trials of its own mRNA-based vaccine and received approval for human trials. 8 Additionally, other Bangladeshi vaccine manufacturing companies are capable of addressing the void in vaccine antigen production. Experts predict that the global COVID-19 vaccine supply could be substantially increased if vaccine manufacturers would share their efforts and technological knowledge with external manufacturers capable of vaccine production. 5 For example, Incepta Vaccine Limited (IVL), the largest human vaccine manufacturing facility in Bangladesh, has signed a memorandum of understanding with Sinopharm, China, for production of the Sinopharm BBIBP-COVID-19 vaccine in Bangladesh. This collaboration will undoubtedly expedite the efforts of Bangladesh to produce viable COVID-19 vaccines in local settings. Along with contract manufacturing, IVL is also in the race to develop its own research and development based COVID-19 vaccine in collaboration with international institutes. 9 Furthermore, Bangladesh has agreed to participate in a clinical trial for a novel nasal-route COVID-19 vaccine, developed by Karolinska Institute, Sweden. With the increasing concern of waning vaccine immunity 10 and effective results from heterologous vaccine priming and boosting,11, 12 Bangladesh should determine its policy and act quickly. Bangladesh has local vaccine research and production capacity at its disposal, along with four distinct COVID-19 vaccines. Looking forward, Bangladesh should focus on hosting clinical trials, including heterologous prime boost trials, to determine vaccine efficacy and long-term protection for its population. Although there is a debate on whether to administer a third vaccine dose as booster, evidence to support recommended schedules and target groups is scarce. 13 A third dose for individuals who have already received two doses should be carefully considered only after two doses of the vaccine have been administered to the remaining unvaccinated people. To ensure maximum vaccine coverage, countries such as Bangladesh should allocate resources to local manufacturers and support large-scale research efforts, clinical trials, cold-chain technology, and international collaboration. Support could be in the form of subsidies, duty-free import of research items, or tax incentives for vaccine manufacturers and research organisations. To bring this pandemic under control, more than 75% of the global population must be vaccinated. 14 This goal becomes increasingly challenging given the unequal distribution and hoarding of vaccines by high-income countries. This inequality could be obviated, however, by strict adherence to the procurement and supply operation under the COVAX initiative. This mandate should serve as a reference for ensuring equitable global access to the COVID-19 vaccine. Discrete high vaccination performance and travel bans from high-income countries will not only be futile in bringing the pandemic under control but will also put all nations at risk unless the global population is universally vaccinated. 15 Initiatives should be undertaken to acquire and distribute vaccines among LMICs. Without such initiatives there remains a growing concern for the persistent presence of COVID-19 hot spots in low-income countries, which increases the risk of escape variants of SARS-COV-2. We declare no competing interests. We would like to acknowledge Nikki Kelvin for editing this manuscript. This work was supported by grants from Canadian Institutes of Health Research, Genome Canada/Atlantic Genome, Research Nova Scotia, Dalhousie Medical Research Foundation, and the Li-Ka Shing Foundation.

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          Durability of mRNA-1273 vaccine–induced antibodies against SARS-CoV-2 variants

          SARS-CoV-2 mutations may diminish vaccine-induced protective immune responses, particularly as antibody titers wane over time. Here, we assess the impact of SARS-CoV-2 variants B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.429 (Epsilon), B.1.526 (Iota), and B.1.617.2 (Delta) on binding, neutralizing, and ACE2-competing antibodies elicited by the vaccine mRNA-1273 over seven months. Cross-reactive neutralizing responses were rare after a single dose. At the peak of response to the second vaccine dose, all individuals had responses to all variants. Binding and functional antibodies against variants persisted in most subjects, albeit at low levels, for 6-months after the primary series of the mRNA-1273 vaccine. Across all assays, B.1.351 had the lowest antibody recognition. These data complement ongoing studies to inform the potential need for additional boost vaccinations.
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            Immune responses against SARS-CoV-2 variants after heterologous and homologous ChAdOx1 nCoV-19/BNT162b2 vaccination

            Currently approved viral vector-based and mRNA-based vaccine approaches against coronavirus disease 2019 (COVID-19) consider only homologous prime-boost vaccination. After reports of thromboembolic events, several European governments recommended using AstraZeneca’s ChAdOx1-nCov-19 (ChAd) only in individuals older than 60 years, leaving millions of already ChAd-primed individuals with the decision to receive either a second shot of ChAd or a heterologous boost with mRNA-based vaccines. However, such combinations have not been tested so far. We used Hannover Medical School’s COVID-19 Contact Study cohort of healthcare professionals to monitor ChAd-primed immune responses before and 3 weeks after booster with ChAd ( n  = 32) or BioNTech/Pfizer’s BNT162b2 ( n  = 55). Although both vaccines boosted prime-induced immunity, BNT162b2 induced significantly higher frequencies of spike-specific CD4 + and CD8 + T cells and, in particular, high titers of neutralizing antibodies against the B.1.1.7, B.1.351 and P.1 variants of concern of severe acute respiratory syndrome coronavirus 2. In a study of healthcare professionals previously vaccinated with ChAdOx-1 nCoV-19, booster vaccination with BNT162b2 elicited more neutralizing antibodies with greater breadth, as well as higher frequencies of virus-specific T cells, than ChAdOx-1 nCoV-19.
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              Heterologous prime-boost COVID-19 vaccination: initial reactogenicity data

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                Author and article information

                Journal
                Lancet Infect Dis
                Lancet Infect Dis
                The Lancet. Infectious Diseases
                Elsevier Ltd.
                1473-3099
                1474-4457
                28 January 2022
                28 January 2022
                Affiliations
                [a ]Department of Microbiology and Immunology, Canadian Center for Vaccinology, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada
                [b ]Department of Genetic Engineering and Biotechnology, Faculty of Biological Sciences, University of Chittagong, Chattogram, Bangladesh
                [c ]Laboratory of Immunity, Shantou University Medical College, Guangdong, China
                [d ]Biotechnology and Genetic Engineering Discipline, Life Science School, Khulna University, Khulna, Bangladesh
                Article
                S1473-3099(22)00028-7
                10.1016/S1473-3099(22)00028-7
                8798084
                35101243
                7aaf8f08-1456-4b2a-9230-adfeba4cbc13
                © 2022 Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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                Infectious disease & Microbiology
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