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News

A review of vaccine efforts against SARS-CoV-2


 

The Journal of Virology published a review by Moore and Klasse that summarizes the herculean efforts to develop a vaccine against SARS-CoV-2 in as small a time frame as possible. They dive deeply into the antibody response against SARS-CoV-2 and what this may portend for vaccine efforts. Here are some of the highlights from the review:

Antibody response to COVID-19 case vary greatly. Almost everyone tested who had symptoms raises an antibody (Ab) response against the virus in the form of IgM, IgG, and IgA (See Section 16-3 of TTM if you want to learn more about Ab structures). The antibody titers begin 1-2 weeks post symptom onset and are elevated for at least several weeks after the infection is cleared. A strong T-cell response is also observed, but it varies considerably from person-to-person. It is difficult to compare across studies because methods of measurement are not standardized. However, convalescent plasma has shown to be effective in ill patients, implying that the Abs have a protective effect. One interesting aspect is we may be missing the boat on the immune response to SARS-CoV-2. Most assays test the blood, while it may be that much more of the protective response is on the epithelial surfaces. The concentration of neutralizing IgA in secretions may be a better indicator. In any case, the Ab response to the real disease can supply a metric for comparison of vaccines, but it may be a poor one.

Ab response to SARS-CoV-2 is confusing. Those with mild symptoms that did not require hospitalization appear to raise a weak antibody response. High antibody titers early in the disease course correlate with sicker patients and poorer disease outcomes It is not clear if the higher concentration of virus, due to severe infection, is driving the Ab response or if the strong Ab response somehow drives the disease process. Strong IgA response is seen in SARS-CoV-2 infections in comparison to influenza where IgA responses are much weaker. The strength of the Ab response varies considerably. Moore and Klasse rightfully caution that comparing Ab response in a vaccine trial to that seen in infected individuals is nearly meaningless.

The duration of the Ab response. Ab titers in infected individuals rise reaching a peak at 30-40 days post-infection. The first studies looking at long-term Ab retention shows a marked decline with a fraction of those infected becoming undetectable. This doesn't, however, mean these individuals have no immunity to the virus, as memory B-cells that can react to the virus are present. Reinfection studies with animals, where they were infected with the virus, allowed to recover, and then reinfected showed that the animal's immune systems protected them against disease. However, the reinfections occurred 5 weeks after the first infection, and there are no reports measuring long-term immunity. Studies with common-cold coronaviruses have shown that humans are susceptible to reinfection with these viruses. But it's not the same virus. Those infected with SARS-CoV-1 and MERS, which both cause much more severe disease, seem to elicit a stronger immune response that appears to last for years.

Cross-reactivity to other coronaviruses. In one study described, 40-60% of people who have never been exposed to SARS-CoV-2 had cross-reactive T-cells, suggesting there is a possibility of some immune protection against SARS-CoV-2 and this may explain the widely varying response individuals have to infection.

The spike protein doesn't seem to be changing much. The spike protein of SARS-CoV-2 does not appear to be mutating in ways that would make it escape detection by the immune response. This also means that Ab therapies that would be developed for SARS-CoV-2 today will probably continue to be effective.

The vaccines fastest out the gate, may not be the best ones to use long term. Nucleic acid vaccines and those developed using other viral platforms to deliver the spike protein elicit an Ab response, but not as strong as an infection. It is not clear if the response generated is protective or if this is even the best thing to measure to gauge success. As we learn more about the virus, better vaccines will be developed.

We need to measure the efficacy of the vaccine against the virus. It is imperative that vaccine trials are measured by how well they block infection and not by their antibody response only. It may be tempting for governments to rush a vaccine into production if it demonstrates an immune response, but this would be unwise. An immune response does not mean that a vaccine will protect against disease, and it is possible, tho unlikely, it could even worsen the disease. We need to wait for these vaccine trials to fully play out before we begin vaccinating entire populations.