COVID-19 Vaccines: “Warp Speed” Needs Mind Melds, Not Warped Minds

Abstract

In this review, we address issues that relate to the rapid “Warp Speed” development of vaccines to counter the COVID-19 pandemic. We review the antibody response that is triggered by SARS-CoV-2 infection of humans, and how it may inform vaccine research. The isolation and properties of neutralizing monoclonal antibodies from COVID-19 patients provide additional information on what vaccines should try to elicit. The nature and longevity of the antibody response to coronaviruses are relevant to the potency and duration of vaccine-induced immunity. We summarize the immunogenicity of leading vaccine candidates tested to date in animals and humans, and discuss the outcome and interpretation of virus-challenge experiments in animals. By far the most immunogenic vaccine candidates for antibody responses are recombinant proteins, which are not included in the initial wave of “Warp Speed” immunogens. A substantial concern for SARS-CoV-2 vaccines is adverse events, which we review by considering what was seen in studies of SARS-CoV-1 and MERS-CoV vaccines. We conclude by outlining the possible outcomes of the “Warp Speed” vaccine program, which range from the hoped-for rapid success to a catastrophic adverse influence on vaccine uptake generally.

Capsid-like particles decorated with the SARS2-CoV-2 receptor-binding domain elicit strong virus neutralization activity

“…The ideal SARS-CoV-2 vaccine should be safe, and capable of activating a long-term protective immune response. High immunogenicity is pivotal for vaccine efficacy and represents a fundamental challenge for the vaccine development 53 . In the context of COVID-19, the elderly carry an increased risk of serious illness 54 , but it is also well known that this group generally responds less effectively to vaccination 55,56 .…”

“…Serum samples from convalescent patients showed similar neutralization titers as those measured for mouse sera obtained after a prime immunization of RBDn-CLP. A recent review, compiling all the latest data on SARS-CoV-2 vaccine development, suggests that a >50% neutralizing titers at an endpoint titer dilution of 100-500 would be needed to confer protection 53 . In relation to this, our RBDn-CLP vaccine induces 100% neutralization at our highest tested serum dilution >10,000 (or >2560, supplementary fig.…”

“…Indeed, when looking at emerging data on SARS-CoV-2 vaccine development, it appears that the vaccines that are fast to produce (i.e. genetic and virus vectors) might not be able to elicit antibody titers sufficient to confer long lived protection 53 . Additionally, vaccines have many times failed due to low immunogenicity when testing in human clinical trials, despite having produced encouraging results in preclinical models 65,66 .…”

“…Additionally, vaccines have many times failed due to low immunogenicity when testing in human clinical trials, despite having produced encouraging results in preclinical models 65,66 . Thus, in the case of SARS-CoV-2, it seems that recombinant proteins or killed/attenuated virus vaccines would most likely be the ones enabling responses strong enough for protection 53 . However, killed or live-attenuated viruses has potential safety concerns.…”

Efficient production of Moloney murine leukemia virus-like particles pseudotyped with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein

“…Efforts are being made to identify candidate neutralizing antibodies (Nabs) that could block the interaction of SARS-CoV2-S with its receptor and that could be used for treating infected patients (20)(21)(22). Several vaccine strategies for COVID-19 are also intensively pursued, with S protein being the major target (23)(24)(25). These vaccines are produced from different platforms: RNA, DNA, recombinant proteins, viral vector-based or virus-like particles (VLPs), and live attenuated and inactivated viruses (23)(24)(25).…”