Abstract:Recombinant adenovirus type 5 (rAd) has been used as a vaccine platform against many infectious diseases and has been shown to be an effective vaccine vector. The dose of the vaccine varies significantly from study to study, making it very difficult to compare immune responses and vaccine efficacy. This study determined the immune correlates induced by serial dilutions of rAd vaccines delivered intramuscularly (IM) and intranasally (IN) to mice and rats. When immunized IM, mice had substantially higher antibod… Show more
“…1B). This result is consistent with the well-reported observation that immunogenicity after adenovirus vaccination is dose dependent ( 12 , 13 ). However, an unexpected effect was observed after the booster immunization 4 weeks later.…”
SARS-CoV-2 has caused a global pandemic that has infected more than 230 million people worldwide. Although several vaccine candidates have received emergency use authorization (EUA), there is still limited knowledge on how vaccine dosing affects immune responses. We performed mechanistic studies in mice to understand how the priming dose of an adenovirus-based SARS-CoV-2 vaccine affects long-term immunity to SARS-CoV-2. We first primed C57BL/6 mice with an adenovirus serotype 5 vaccine encoding the SARS-CoV-2 spike protein, similar to that used in the CanSino and Sputnik V vaccines. The vaccine prime was administered either at a standard dose or 1000-fold lower dose, followed by a boost with the standard dose four weeks later. Initially, the low dose prime induced lower immune responses relative to the standard dose prime. However, the low dose prime elicited immune responses that were qualitatively superior, and upon boosting, exhibited significantly more potent recall and functional capacity. We also report similar effects with a simian immunodeficiency virus (SIV) vaccine. These findings show an unexpected advantage of fractionating vaccine prime doses, warranting a re-evaluation of vaccine trial protocols for SARS-CoV-2 and other pathogens.
“…1B). This result is consistent with the well-reported observation that immunogenicity after adenovirus vaccination is dose dependent ( 12 , 13 ). However, an unexpected effect was observed after the booster immunization 4 weeks later.…”
SARS-CoV-2 has caused a global pandemic that has infected more than 230 million people worldwide. Although several vaccine candidates have received emergency use authorization (EUA), there is still limited knowledge on how vaccine dosing affects immune responses. We performed mechanistic studies in mice to understand how the priming dose of an adenovirus-based SARS-CoV-2 vaccine affects long-term immunity to SARS-CoV-2. We first primed C57BL/6 mice with an adenovirus serotype 5 vaccine encoding the SARS-CoV-2 spike protein, similar to that used in the CanSino and Sputnik V vaccines. The vaccine prime was administered either at a standard dose or 1000-fold lower dose, followed by a boost with the standard dose four weeks later. Initially, the low dose prime induced lower immune responses relative to the standard dose prime. However, the low dose prime elicited immune responses that were qualitatively superior, and upon boosting, exhibited significantly more potent recall and functional capacity. We also report similar effects with a simian immunodeficiency virus (SIV) vaccine. These findings show an unexpected advantage of fractionating vaccine prime doses, warranting a re-evaluation of vaccine trial protocols for SARS-CoV-2 and other pathogens.
“…15 There are studies that show a patient's immune response resulting from delivery of a vaccine to the lung may equal or exceeds the immune response created by vaccine injection. 16 It has been proposed that a mucosal immune response may be created via particles of the vaccine material depositing on the upper respiratory tract. 17 A systemic immune response may be created via particles of the vaccine material depositing into the deep lung.…”
A novel concept in DNA vaccine design is the creation of an inhaled DNA plasmid construct containing a portion of the coronavirus spike protein for treatment and vaccination. The secretion of a spike protein portion will function
Although Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines have shown efficacy against SARS-CoV-2, it is unknown if coronavirus vaccines can also protect against other coronaviruses that may infect humans in the future. Here, we show that coronavirus vaccines elicit cross-protective immune responses against heterologous coronaviruses. In particular, we show that a Severe Acute Respiratory Syndrome Coronavirus 1 (SARS-CoV-1) vaccine developed in 2004 and known to protect against SARS-CoV-1, confers robust heterologous protection against SARS-CoV-2 in mice.Similarly, prior coronavirus infections conferred heterologous protection against distinct coronaviruses. Cross-reactive immunity was also reported in Coronavirus Disease 2019 (COVID-19) patients and humans who received SARS-CoV-2 vaccines, and transfer of plasma from these individuals into mice improved protection against coronavirus challenges. These findings provide the first demonstration that coronavirus vaccines (and prior coronavirus infections) can confer broad protection against heterologous coronaviruses, providing a rationale for universal coronavirus vaccines.
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