Abstract
The 2009 “swine flu” pandemic outbreak demonstrated the limiting capacity for egg-based vaccines with respect to global vaccine supply within a timely fashion. New vaccine platforms that efficiently can quench pandemic influenza emergences are urgently needed. Since 2009, there has been a profound development of new vaccine platform technologies with respect to prophylactic use in the population, including DNA vaccines. These vaccines are particularly well suited for global pandemic responses as the DNA format is temperature stable and the production process is cheap and rapid. Here, we show that by targeting influenza antigens directly to antigen presenting cells (APC), DNA vaccine efficacy equals that of conventional technologies. A single dose of naked DNA encoding hemagglutinin (HA) from influenza/A/California/2009 (H1N1), linked to a targeting moiety directing the vaccine to major histocompatibility complex class II (MHCII) molecules, raised similar humoral immune responses as the adjuvanted split virion vaccine Pandemrix, widely administered in the 2009 pandemic. Both vaccine formats rapidly induced serum antibodies that could protect mice already 8 days after a single immunization, in contrast to the slower kinetics of a seasonal trivalent inactivated influenza vaccine (TIV). Importantly, the DNA vaccine also elicited cytotoxic T-cell responses that reduced morbidity after vaccination, in contrast to very limited T-cell responses seen after immunization with Pandemrix and TIV. These data demonstrate that DNA vaccines has the potential as a single dose platform vaccine, with rapid protective effects without the need for adjuvant, and confirms the relevance of naked DNA vaccines as candidates for pandemic preparedness.
Highlights
Vaccines are highly efficient at prophylactic relief against infectious diseases, and vaccines against influenza, measles, and tuberculosis are examples of vaccines that annually save many lives [1, 2]
We have previously found that targeting of HA to major histocompatibility complex class II (MHCII) molecules was superior at raising protective antibodies following vaccination, as compared to eight other antigen presenting cells (APC) specific targeting moieties [27]
The plasmids encoding aMHCII-HA were formulated in a physiological saline solution (NaCl), while Pandemrix was formulated with the adjuvant solution AS03
Summary
Vaccines are highly efficient at prophylactic relief against infectious diseases, and vaccines against influenza, measles, and tuberculosis are examples of vaccines that annually save many lives [1, 2]. DNA Vaccine for Pandemic Relief influenza vaccines based on egg-production had several shortcomings. Rapid availability of well-matched vaccines is key [5,6,7]. In 2009, the conventional vaccines against pandemic influenza was produced within 6 months, which represents a record fast production for this vaccine format [8]. It should be no surprise that the frontrunner vaccines developed against SARS-CoV-2 in 2020 were based on more versatile technologies [9,10,11]. DNA vaccines are rapid to produce, easy to store and deploy independent of a cold chain, and highly versatile with respect to updating the vaccine to match new antigenic variants [12]. The development of minimally invasive DNA vaccine delivery systems, such as microneedle patches [13, 14] or needle-free jet delivery [15, 16], makes naked DNA vaccines highly applicable in a mass vaccination scenario
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