With autumn’s rapid approach, considerable anticipation surrounds the possibility of a vaccine breakthrough by January 2021.
As a physician-scientist and infectious diseases specialist affiliated with the University of Virginia, my work encompasses patient care and dedicated research into COVID-19.
I am frequently queried about the certainty of researchers developing an effective COVID-19 vaccine, especially given the persistent absence of one for HIV, the virus responsible for AIDS.
This review outlines the current research landscape, projects our position in five months, and provides reasons for optimism regarding the eventual availability of a COVID-19 vaccine.
1. The Human Immune System’s Capacity to Resolve COVID-19
In a substantial majority of COVID-19 cases, estimated at up to 99 percent, individuals successfully recuperate from the infection, leading to the clearance of the virus from their system.
While some recovered individuals might harbor residual low levels of the virus for up to three months post-infection, the transmission capability to others typically ceases 10 days after the onset of symptoms in most scenarios.
Consequently, creating a vaccine for the novel coronavirus is anticipated to be considerably more straightforward than for pathogens like HIV, where the immune system’s natural resolution is compromised. Unlike HIV, SARS-CoV-2 exhibits less propensity for mutation, rendering it a more manageable target for immune system intervention and vaccine efficacy.
2. Targeting the Spike Protein to Confer Immunity
A primary mechanism by which a vaccine will offer protection is by stimulating the generation of antibodies directed against the spike protein adorning the surface of SARS-CoV-2, the antecedent of COVID-19.
The virus inherently requires its spike protein to establish attachment and entry into human cells for replication. Scientific findings have demonstrated that antibodies, mirroring those produced by the human immune response, can bind to and neutralize the spike protein, thereby impeding the coronavirus’s ability to infect host cells in laboratory settings.
Vaccines currently undergoing clinical evaluation have exhibited the capacity to elicit anti-spike antibodies that effectively inhibit viral entry into cells in vitro.
A minimum of seven distinct entities have engineered monoclonal antibodies – laboratory-derived immunoglobulins designed to recognize the spike protein. These antibodies are progressing through clinical trials to ascertain their protective potential against infection in individuals exposed to the virus, such as through household contact.
Furthermore, monoclonal antibodies may prove beneficial in therapeutic applications. Administered during an active infection, a dose of these specialized antibodies could neutralize the virus, affording the immune system an opportunity to mount its own response and combat the pathogen.
3. The Spike Glycoprotein as a Multifaceted Target
The spike protein presents numerous sites amenable to antibody binding, facilitating the neutralization of the virus. This characteristic is advantageous, as the abundance of vulnerable points makes it challenging for the virus to undergo mutations that would circumvent vaccine-induced immunity.
A significant number of mutations across the spike protein would be necessary for the virus to evade neutralizing anti-spike antibodies. Such extensive genetic alterations to the spike protein would inevitably compromise its structural integrity, rendering it incapable of binding to ACE2, a crucial step for infecting human cells.
4. Established Protocols for Safe Vaccine Development
The safety profile of a novel COVID-19 vaccine is enhanced by the accumulated knowledge researchers possess regarding potential adverse reactions and effective mitigation strategies.
One historically observed side effect is antibody-dependent enhancement of infection. This phenomenon occurs when antibodies fail to neutralize the virus but instead facilitate its entry into cells via a receptor typically used by antibodies.
Investigations have revealed that by employing immunization with the spike protein, high titers of neutralizing antibodies can be achieved, thereby reducing the risk of enhancement.
A second potential concern associated with certain vaccine candidates is an allergic reaction manifesting as pulmonary inflammation, a scenario observed in individuals who received a respiratory syncytial virus vaccine in the 1960s.
This poses a significant risk, as inflammation within the lung’s air spaces can lead to respiratory distress. However, current scientific understanding enables the design of vaccines that circumvent this particular allergic response.
5. A Diversified Portfolio of Vaccine Candidates
The United States government is actively supporting the development of multiple distinct vaccine candidates through initiatives such as Operation Warp Speed.
The overarching objective of Operation Warp Speed is to facilitate the delivery of 300 million doses of a safe and efficacious vaccine by January 2021.
Significant financial commitment from the US government, totaling US$8 billion, has been allocated across seven different COVID-19 vaccine programs.
By investing in a portfolio of COVID-19 vaccines, the government mitigates risk. The success of a single vaccine candidate that demonstrates safety and efficacy in clinical trials is sufficient for its widespread availability to the American population in 2021.
6. Advancement Through Phase I and II Clinical Trials
Phase I and II trials are primarily designed to assess vaccine safety and its ability to elicit an immune response. Preliminary results from three distinct vaccine trials have been encouraging, demonstrating the induction of anti-spike neutralizing antibody levels that are two to four times higher than those observed in COVID-19 convalescents.
Moderna, Oxford, and China-based company CanSino have collectively reported favorable safety profiles for their respective vaccines in Phase I and II trials.
7. Commencement of Phase III Clinical Trials
Phase III trials represent the concluding stage of vaccine development, involving the rigorous testing of the vaccine in tens of thousands of participants to ascertain its efficacy in preventing SARS-CoV-2 infection and to confirm its safety.
The vaccine developed by Moderna in collaboration with the NIH, along with the vaccine from Oxford-AstraZeneca, initiated Phase III trials in July. Additional COVID-19 vaccine candidates are slated to commence their Phase III trials in the ensuing weeks.
8. Expediting Vaccine Manufacturing and Distribution
Operation Warp Speed is providing financial backing for the large-scale production of millions of vaccine doses and is supporting industrial-scale manufacturing even in advance of definitive evidence of vaccine efficacy and safety.
The strategic advantage of this approach lies in the pre-existing stockpile of the vaccine, which can be rapidly distributed upon successful completion and approval of Phase III trials, without compromising the thoroughness of safety and efficacy assessments.
This represents a more cautious strategy compared to that of Russia, which is administering a vaccine to the public before its safety and efficacy have been conclusively demonstrated in Phase III trials.
9. Pre-emptive Contracting of Vaccine Distributors
McKesson Corp., recognized as the largest vaccine distributor in the United States, has already entered into an agreement with the CDC for the distribution of a COVID-19 vaccine to various administration sites, including clinics and hospitals.
It is my considered opinion that by late 2020, we will have definitive information regarding the safety, precise efficacy, and selection of specific COVID-19 vaccines for the immunization of the US population in 2021.
