ABSTRACT
Several effective vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and implemented in the population. However, the current production capacity falls short of meeting global demand. Therefore, it is crucial to further develop novel vaccine platforms that can bridge the distribution gap. AVX/COVID-12 is a vector-based vaccine that utilizes the Newcastle Disease virus (NDV) to present the SARS-CoV-2 spike protein to the immune system. This study analyses the antigenicity of the vaccine candidate by examining antibody binding and T-cell activation in individuals infected with SARS-CoV-2 or variants of concern (VOCs), as well as in healthy volunteers who received coronavirus disease 2019 (COVID-19) vaccinations. Our findings indicate that the vaccine effectively binds antibodies and activates T-cells in individuals who received 2 or 3 doses of BNT162b2 or AZ/ChAdOx-1-S vaccines. Furthermore, the stimulation of T-cells from patients and vaccine recipients with AVX/COVID-12 resulted in their proliferation and secretion of interferon-gamma (IFN-{gamma}) in both CD4+ and CD8+ T-cells. In conclusion, the AVX/COVID-12 vectored vaccine candidate demonstrates the ability to stimulate robust cellular responses and is recognized by antibodies primed by the spike protein present in SARS-CoV-2 viruses that infected patients, as well as in the mRNA BNT162b2 and AZ/ChAdOx-1-S vaccines. These results support the inclusion of the AVX/COVID-12 vaccine as a booster in vaccination programs aimed at addressing COVID-19 caused by SARS-CoV-2 and its VOCs.
Subject(s)
COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
Neutralizing antibodies correlate with protection against SARS-CoV-2. Recent studies, however, show that binding antibody titers, in the absence of robust neutralizing activity, also correlate with protection from disease progression. Non-neutralizing antibodies cannot directly protect from infection but may recruit effector cells thus contribute to the clearance of infected cells. Also, they often bind conserved epitopes across multiple variants. We characterized 42 human mAbs from COVID-19 vaccinated individuals. Most of these antibodies exhibited no neutralizing activity in vitro but several non-neutralizing antibodies protected against lethal challenge with SARS-CoV-2 in different animal models. A subset of those mAbs showed a clear dependence on Fc-mediated effector functions. We determined the structures of three non-neutralizing antibodies with two targeting the RBD, and one that targeting the SD1 region. Our data confirms the real-world observation in humans that non-neutralizing antibodies to SARS-CoV-2 can be protective.
Subject(s)
COVID-19ABSTRACT
Background: The urgent need for safe, effective, and economical coronavirus disease 2019 (COVID-19) vaccines, especially for booster campaigns targeting vulnerable populations, prompted the development of the AVX/COVID-12 vaccine candidate. AVX/COVD-12 is based in a Newcastle disease virus La Sota (NDV-LaSota) recombinant viral vector. This vaccine expresses a stabilized version of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), specifically the ancestral Wuhan strain. The study aimed to assess its safety, immunogenicity, and potential efficacy as an anti-COVID-19 booster vaccine. Methods: In a phase II/III clinical trial conducted from November 9, 2022, to September 11, 2023, a total of 4,056 volunteers were enrolled. Participants received an intramuscular booster dose of either AVX/COVID-12 or AZ/ChAdOx-1-S vaccines. Safety, immunogenicity, and potential efficacy were assessed through various measures, including neutralizing antibody titers, interferon (IFN)-γ-producing CD4+ T cells, and CD8+ T cells. The evaluation also involved immunobridging, utilizing the AZ/ChAdOx-1-S vaccine as an active comparator, and monitoring the incidence of COVID-19 cases. Findings: The AVX/COVID-12 vaccine induced neutralizing antibodies against both the ancestral SARS-CoV-2 and the BA.2 and BA.5 Omicron variants. The geometric mean ratio of neutralizing antibody titers between individuals immunized with the AVX/COVID-12 vaccine and those with the AZ/ChAdOx-1-S vaccine at 14 days is 0.96, with a confidence interval (CI) of 0.85-1.06. The outcome aligns with the non-inferiority criterion recommended by the World Health Organization (WHO), indicating a lower limit of the CI greater than or equal to 0.67. Induction of IFN-γ-producing CD8+ T cells at day 14 post-immunization was exclusively observed in the AVX/COVID-12 group. Finally, a trend suggested a potentially lower incidence of COVID-19 cases in AVX/COVID-12 boosted volunteers compared to AZ/ChAdOx-1-S recipients. Conclusion: The AVX/COVID-12 vaccine proved safe, well-tolerated, and immunogenic. AVX/COVID-12 meets the WHO non-inferiority standard compared to AZ/ChAdOx-1-S. These results strongly advocate for AVX/COVID-12 as a viable booster dose, supporting its utilization in the population.
Subject(s)
Coronavirus Infections , Severe Acute Respiratory Syndrome , COVID-19 , Newcastle DiseaseABSTRACT
BackgroundThe global inequity in coronavirus disease 2019 (COVID-19) vaccine distribution, primarily affecting low- and middle-income countries (LMICs), highlights the urgent need for innovative and cost-effective vaccine technologies to address availability disparities. This is crucial for achieving and sustaining widespread immunity and protecting vulnerable populations during future booster campaigns. MethodsTo address this need, we conducted a phase II clinical trial evaluating the safety and immunogenicity of the AVX/COVID-12 "Patria" vaccine as a booster dose. The vaccine was administered through both intramuscular (IM) and intranasal (IN) routes to participants who had previously received severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines based on adenoviral technology, inactivated virus, or mRNA technology. The inclusion criterion involved individuals with initial anti-spike IgG titers below 1,200 U/mL, allowing observation of the booster effect induced by vaccination. ResultsImmunization with AVX/COVID-12 resulted in a significant (>2.5 times) increase in neutralizing antibodies against the original Wuhan strain and variants of concern (VOCs) such as Alpha, Beta, Delta, and Omicron (BA.2 and BA.5). This immune response was accompanied by cellular interferon-gamma (IFN-{gamma}) production, indicating a robust and multifaceted reaction. ConclusionsThe administration of AVX/COVID-12 as a booster dose, whether through IM or IN routes, was safe and well-tolerated. The vaccine extended immune responses not only against the original Wuhan-1 strain but also against various VOCs. Its ability to enhance preexisting immune responses suggests a potential contribution to expanding and sustaining herd immunity within the population.
Subject(s)
Coronavirus Infections , COVID-19 , Newcastle DiseaseABSTRACT
Seasonal coronaviruses have been circulating widely in the human population for many years. With increasing age, humans are more likely to have been exposed to these viruses and to have developed immunity against them. It has been hypothesized that this immunity to seasonal coronaviruses may provide partial protection against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it has also been shown that coronavirus disease 2019 (COVID-19) vaccination induces a back-boosting effects against the spike proteins of seasonal betacoronaviruses. In this study, we tested if immunity to the seasonal coronavirus spikes from OC43, HKU1, 229E or NL63 would confer protection against SARS-CoV-2 challenge in a mouse model, and whether pre-existing immunity against these spikes would weaken the protection afforded by mRNA COVID-19 vaccination. We found that mice vaccinated with the seasonal coronavirus spike proteins had no increased protection as compared to the negative controls. While a negligible back-boosting effect against betacoronavirus spike proteins was observed after SARS-CoV-2 infection, there was no negative original antigenic sin-like effect on the immune response and protection induced by SARS-CoV-2 mRNA vaccination in animals with pre-existing immunity to seasonal coronavirus spike proteins.
Subject(s)
Coronavirus Infections , COVID-19ABSTRACT
Equitable access to vaccines is necessary to limit the global impact of the coronavirus disease 2019 (COVID-19) pandemic and the emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. In previous studies, we described the development of a low-cost vaccine based on a Newcastle Disease virus (NDV) expressing the prefusion stabilized spike protein from SARS-CoV-2, named NDV-HXP-S. Here, we present the development of next-generation NDV-HXP-S variant vaccines, which express the stabilized spike protein of the Beta, Gamma and Delta variants of concerns (VOC). Combinations of variant vaccines in bivalent, trivalent and tetravalent formulations were tested for immunogenicity and protection in mice. We show that the trivalent preparation, composed of the ancestral Wuhan, Beta and Delta vaccines, substantially increases the levels of protection and of cross-neutralizing antibodies against mismatched, phylogenetically distant variants, including the currently circulating Omicron variant.
Subject(s)
COVID-19 , Coronavirus InfectionsABSTRACT
There is still a need for safe, efficient and low-cost coronavirus disease 2019 (COVID-19) vaccines that can stop transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we evaluated a vaccine candidate based on a live recombinant Newcastle disease virus (NDV) that expresses a stable version of the spike protein in infected cells as well as on the surface of the viral particle (AVX/COVID-12-HEXAPRO, also known as NDV-HXP-S). This vaccine candidate can be grown in embryonated eggs at low cost similar to influenza virus vaccines and it can also be administered intranasally, potentially to induce mucosal immunity. We evaluated this vaccine candidate in prime-boost regimens via intramuscular, intranasal, or intranasal followed by intramuscular routes in an open label non-randomized non-placebo-controlled phase I clinical trial in Mexico in 91 volunteers. The primary objective of the trial was to assess vaccine safety and the secondary objective was to determine the immunogenicity of the different vaccine regimens. In the interim analysis reported here, the vaccine was found to be safe and the higher doses tested were found to be immunogenic when given intramuscularly or intranasally followed by intramuscular administration, providing the basis for further clinical development of the vaccine candidate. The study is registered under ClinicalTrials.gov identifier NCT04871737. Funding was provided by Avimex and CONACYT.
Subject(s)
COVID-19 , Coronavirus InfectionsABSTRACT
Production of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and middle-income countries is needed. NDV-HXP-S is an inactivated egg-based Newcastle disease virus (NDV) vaccine expressing the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Wuhan-Hu-1. The spike protein was stabilized and incorporated into NDV virions by removing the polybasic furin cleavage site, introducing the transmembrane domain and cytoplasmic tail of the fusion protein of NDV, and introducing six prolines for stabilization in the prefusion state. Vaccine production and clinical development was initiated in Vietnam, Thailand, and Brazil. Here the interim results from the first stage of the randomized, dose-escalation, observer-blind, placebo-controlled, phase 1/2 trial conducted at the Hanoi Medical University (Vietnam) are presented. Healthy adults aged 18-59 years, non-pregnant, and with self-reported negative history for SARS-CoV-2 infection were eligible. Participants were randomized to receive one of five treatments by intramuscular injection twice, 28 days apart: 1 mcg +/- CpG1018 (a toll-like receptor 9 agonist), 3 mcg alone, 10 mcg alone, or placebo. Participants and personnel assessing outcomes were masked to treatment. The primary outcomes were solicited adverse events (AEs) during 7 days and subject-reported AEs during 28 days after each vaccination. Investigators further reviewed subject-reported AEs. Secondary outcomes were immunogenicity measures (anti-spike immunoglobulin G [IgG] and pseudotyped virus neutralization). This interim analysis assessed safety 56 days after first vaccination (day 57) in treatment-exposed individuals and immunogenicity through 14 days after second vaccination (day 43) per protocol. Between March 15 and April 23, 2021, 224 individuals were screened and 120 were enrolled (25 per group for active vaccination and 20 for placebo). All subjects received two doses. The most common solicited AEs among those receiving active vaccine or placebo were all predominantly mild and included injection site pain or tenderness (<58%), fatigue or malaise (<22%), headache (<21%), and myalgia (<14%). No higher proportion of the solicited AEs were observed for any group of active vaccine. The proportion reporting vaccine-related AEs during the 28 days after either vaccination ranged from 4% to 8% among vaccine groups and was 5% in controls. No vaccine-related serious adverse event occurred. The immune response in the 10 mcg formulation group was highest, followed by 1 mcg+CpG1018, 3 mcg, and 1 mcg formulations. Fourteen days after the second vaccination, the geometric mean concentrations (GMC) of 50% neutralizing antibody against the homologous Wuhan-Hu-1 pseudovirus ranged from 56.07 IU/mL (1 mcg, 95% CI 37.01, 84.94) to 246.19 IU/mL (10 mcg, 95% CI 151.97, 398.82), with 84% to 96% of vaccine groups attaining a [≥] 4-fold increase over baseline. This was compared to a panel of human convalescent sera (N=29, 72.93 95% CI 33.00-161.14). Live virus neutralization to the B.1.617.2 (Delta) variant of concern was reduced but in line with observations for vaccines currently in use. Since the adjuvant has shown modest benefit, GMC ratio of 2.56 (95% CI, 1.4 - 4.6) for 1 mcg +/- CpG1018, a decision was made not to continue studying it with this vaccine. NDV-HXP-S had an acceptable safety profile and potent immunogenicity. The 3 mcg dose was advanced to phase 2 along with a 6 mcg dose. The 10 mcg dose was not selected for evaluation in phase 2 due to potential impact on manufacturing capacity. ClinicalTrials.gov NCT04830800.
Subject(s)
Coronavirus Infections , Pain , Headache , COVID-19 , Myalgia , FatigueABSTRACT
NDV-HXP-S is a recombinant Newcastle disease virus based-vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which expresses an optimized (HexaPro) spike protein on its surface. The vaccine can be produced in embryonated chicken eggs using the same process as that employed for the production of influenza virus vaccines. Here we performed a secondary analysis of the antibody responses after vaccination with inactivated NDV-HXP-S in a Phase I clinical study in Thailand. The SARS-CoV-2 neutralizing and spike binding activity of NDV-HXP-S post-vaccination serum samples was compared to that of matched samples from mRNA BNT162b2 (Pfizer) vaccinees. Neutralizing activity of sera from NDV-HXP-S vaccinees was comparable to that of individuals vaccinated with BNT162b2. Interstingly, the spike binding activity of the NDV-HXP-S vaccinee samples was lower than that of sera obtained from individuals vaccinated with the mRNA vaccine. This let us to calculate ratios between binding and neutralizing antibody titers. Samples from NDV-HXP-S vaccinees had binding to neutralizing activity ratios similar to those of convalescent sera suggesting a very high proportion of neutralizing antibodies and low non-neutralizing antibody titers. Further analysis showed that, in contrast to mRNA vaccination, which induces strong antibody titers to the receptor binding domain (RBD), the N-terminal domain, and the S2 domain, NDV-HXP-S vaccination induces a very RBD focused response with little reactivity to S2. This explains the high proportion of neutralizing antibodies since most neutralizing epitopes are located in the RBD. In conclusion, vaccination with inactivated NDV-HXP-S induces a high proportion of neutralizing antibodies and absolute neutralizing antibody titers comparable to those after mRNA vaccination.
Subject(s)
COVID-19 , Coronavirus InfectionsABSTRACT
The continual emergence of SARS-CoV-2 variants of concern, in particular the newly emerged Omicron (B.1.1.529) variant, has rendered ineffective a number of previously EUA approved SARS-CoV-2 neutralizing antibody therapies. Furthermore, even those approved antibodies with neutralizing activity against Omicron are reportedly ineffective against the subset of Omicron variants that contain a R346K substitution, demonstrating the continued need for discovery and characterization of candidate therapeutic antibodies with the breadth and potency of neutralizing activity required to treat newly diagnosed COVID-19 linked to recently emerged variants of concern. Following a campaign of antibody discovery based on the vaccination of Harbour H2L2 mice with defined SARS-CoV-2 spike domains, we have characterized the activity of a large collection of Spike-binding antibodies and identified a lead neutralizing human IgG1 LALA antibody, STI-9167. STI-9167 has potent, broad-spectrum neutralizing activity against the current SARS-COV-2 variants of concern and retained activity against the Omicron and Omicron + R346K variants in both pseudotype and live virus neutralization assays. Furthermore, STI-9167 nAb administered intranasally or intravenously provided protection against weight loss and reduced virus lung titers to levels below the limit of quantitation in Omicron-infected K18-hACE2 transgenic mice. With this established activity profile, a cGMP cell line has been developed and used to produce cGMP drug product intended for use in human clinical trials.
Subject(s)
Severe Acute Respiratory Syndrome , Weight Loss , COVID-19ABSTRACT
Summary Background Production of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and middle-income countries is needed. NDV-HXP-S is an inactivated egg-based Newcastle disease virus vaccine expressing the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It’s being developed in Thailand, Vietnam, and Brazil; herein are initial results from Thailand. Methods This phase 1 stage of a randomised, dose-escalation, observer-blind, placebo-controlled, phase 1/2 trial was conducted at the Vaccine Trial Centre, Mahidol University (Bangkok). Healthy adults aged 18-59 years, non-pregnant and negative for SARS-CoV-2 antibodies were eligible. Participants were block randomised to receive one of six treatments by intramuscular injection twice, 28 days apart: 1 µg±CpG1018 (a toll-like receptor 9 agonist), 3 µg±CpG1018, 10 µg, or placebo. Participants and personnel assessing outcomes were masked to treatment. The primary outcomes were solicited and spontaneously reported adverse events (AEs) during 7 and 28 days after each vaccination, respectively. Secondary outcomes were immunogenicity measures (anti-S IgG and pseudotyped virus neutralisation). An interim analysis assessed safety at day 57 in treatment-exposed individuals and immunogenicity through day 43 per protocol. ClinicalTrials.gov ( NCT04764422 ). Findings Between March 20 and April 23, 2021, 377 individuals were screened and 210 were enrolled (35 per group); all received dose one; five missed dose two. The most common solicited AEs among vaccinees, all predominantly mild, were injection site pain (<63%), fatigue (<35%), headache (<32%), and myalgia (<32%). The proportion reporting a vaccine-related AE ranged from 5·7% to 17·1% among vaccine groups and was 2·9% in controls; there was no vaccine-related serious adverse event. The 10 µg formulation’s immunogenicity ranked best, followed by 3 µg+CpG1018, 3 µg, 1 µg+CpG1018, and 1 µg formulations. On day 43, the geometric mean concentrations of 50% neutralising antibody ranged from 122·23 IU/mL (1 µg, 95% CI 86·40-172·91) to 474·35 IU/mL (10 µg, 95% CI 320·90-701·19), with 93·9% to 100% of vaccine groups attaining a ≥4-fold increase over baseline. Interpretation NDV-HXP-S had an acceptable safety profile and potent immunogenicity. The 3 µg and 3 µg+CpG1018 formulations advanced to phase 2. Funding National Vaccine Institute (Thailand), National Research Council (Thailand), Bill & Melinda Gates Foundation, National Institutes of Health (USA)
Subject(s)
Coronavirus Infections , Encephalomyelitis, Acute Disseminated , COVID-19 , Musculoskeletal Pain , Newcastle DiseaseABSTRACT
Rapid development of coronavirus disease 2019 (COVID-19) vaccines and expedited authorization for use and approval has been proven beneficial to mitigate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread and given hope in this desperate situation. It is believed that sufficient supplies and equitable allocations of vaccines are necessary to limit the global impact of the COVID-19 pandemic and the emergence of additional variants of concern. We have developed a COVID-19 vaccine based on Newcastle disease virus (NDV) that can be manufactured at high yields in embryonated eggs. Here we provide evidence that the NDV vector expressing an optimized spike antigen (NDV-HXP-S), upgraded from our previous construct, is a versatile vaccine that can be used live or inactivated to induce strong antibody responses and to also cross-neutralize variants of concern. The immunity conferred by NDV-HXP-S effectively counteracts SARS-CoV-2 infection in mice and hamsters. It is noteworthy that vaccine lots produced by existing egg-based influenza virus vaccine manufacturers in Vietnam, Thailand and Brazil exhibited excellent immunogenicity and efficacy in hamsters, demonstrating that NDV-HXP-S vaccines can be quickly produced at large-scale to meet global demands.
Subject(s)
Coronavirus Infections , COVID-19ABSTRACT
Rapid development of coronavirus disease 2019 (COVID-19) vaccines and expedited authorization for use and approval has been proven beneficial to mitigate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread and given hope in this desperate situation. It is believed that sufficient supplies and equitable allocations of vaccines are necessary to limit the global impact of the COVID-19 pandemic and the emergence of additional variants of concern. We have developed a COVID-19 vaccine based on Newcastle disease virus (NDV) that can be manufactured at high yields in embryonated eggs. Here we provide evidence that the NDV vector expressing an optimized spike antigen (NDV-HXP-S), upgraded from our previous construct, is a versatile vaccine that can be used live or inactivated to induce strong antibody responses and to also cross-neutralize variants of concern. The immunity conferred by NDV-HXP-S effectively counteracts SARS-CoV-2 infection in mice and hamsters. It is noteworthy that vaccine lots produced by existing egg-based influenza virus vaccine manufacturers in Vietnam, Thailand and Brazil exhibited excellent immunogenicity and efficacy in hamsters, demonstrating that NDV-HXP-S vaccines can be quickly produced at large-scale to meet global demands.
Subject(s)
Coronavirus Infections , COVID-19ABSTRACT
A successful SARS-CoV-2 vaccine must be not only safe and protective but must also meet the demand on a global scale at low cost. Using the current influenza virus vaccine production capacity to manufacture an egg-based inactivated Newcastle disease virus (NDV)/SARS-CoV-2 vaccine would meet that challenge. Here, we report pre-clinical evaluations of an inactivated NDV chimera stably expressing the membrane-anchored form of the spike (NDV-S) as a potent COVID-19 vaccine in mice and hamsters. The inactivated NDV-S vaccine was immunogenic, inducing strong binding and/or neutralizing antibodies in both animal models. More importantly, the inactivated NDV-S vaccine protected animals from SARS-CoV-2 infections or significantly attenuated SARS-CoV-2 induced disease. In the presence of an adjuvant, antigen-sparing could be achieved, which would further reduce the cost while maintaining the protective efficacy of the vaccine.
Subject(s)
COVID-19ABSTRACT
Due to the lack of protective immunity of humans towards the newly emerged SARS-CoV-2, this virus has caused a massive pandemic across the world resulting in hundreds of thousands of deaths. Thus, a vaccine is urgently needed to contain the spread of the virus. Here, we describe Newcastle disease virus (NDV) vector vaccines expressing the spike protein of SARS-CoV-2 in its wild type or a pre-fusion membrane anchored format. All described NDV vector vaccines grow to high titers in embryonated chicken eggs. In a proof of principle mouse study, we report that the NDV vector vaccines elicit high levels of antibodies that are neutralizing when the vaccine is given intramuscularly. Importantly, these COVID-19 vaccine candidates protect mice from a mouse-adapted SARS-CoV-2 challenge with no detectable viral titer and viral antigen in the lungs. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe spike (S) protein of the SARS-CoV-2 is the major antigen that notably induces neutralizing antibodies to block viral entry. Many COVID-19 vaccines are under development, among them viral vectors expressing the S protein of SARS-CoV-2 exhibit many benefits. Viral vector vaccines have the potential of being used as both live or inactivated vaccines and they can induce Th1 and Th2-based immune responses following different immunization regimens. Additionally, viral vector vaccines can be handled under BSL-2 conditions and they grow to high titers in cell cultures or other species restricted-hosts. For a SARS-CoV-2 vaccine, several viral vectors are being tested, such as adenovirus, measles virus and Modified vaccinia Ankara. Added value of this studyThe NDV vector vaccine against SARS-CoV-2 described in this study has advantages similar to those of other viral vector vaccines. But the NDV vector can be amplified in embryonated chicken eggs, which allows for high yields and low costs per dose. Also, the NDV vector is not a human pathogen, therefore the delivery of the foreign antigen would not be compromised by any pre-existing immunity in humans. Finally, NDV has a very good safety record in humans, as it has been used in many oncolytic virus trials. This study provides an important option for a cost-effective SARS-CoV-2 vaccine. Implications of all the available evidenceThis study informs of the value of a viral vector vaccine against SARS-CoV-2. Specifically, for this NDV based SARS-CoV-2 vaccine, the existing egg-based influenza virus vaccine manufactures in the U.S. and worldwide would have the capacity to rapidly produce hundreds of millions of doses to mitigate the consequences of the ongoing COVID-19 pandemic.