Authored by: Venkat Rao
Nothing is straightforward when it comes to published literature on the effectiveness of COVID-19 vaccination and boosters. With a plurality of literature from scientific investigations and those reported in mass media, most discourse tend to offer guidance of limited practical utility to the general public.
In the just published report in the Journal of the American Medical Association, researchers from Singapore report COVID-19 mRNA booster vaccines offered protection against sever COVID-19 by the Omicron variant for at least six months, whereas three doses of an inactivated virus-vector vaccine provided more protection than two doses, but not as protective as three doses of mRNA vaccines. In this cohort study involving more than 2.4 million individuals, the study reported mRNA booster effectiveness against severe COVID-19 was 87.4% for up to 6 months, compared to a virus-inactivated booster effectiveness at 69.6% for the same post-vaccinated period. These results indicate a 3-dose regimen of mRNA vaccine affords better and steady protection compared to a 2-dose regimen of virus-inactivated vaccine for a comparable post-vaccination period of six months, supporting boosting following initial vaccination.
A study with a similar design in the just-published Lancet Infectious Disease report on the mRNA vaccine boosters against Omicron variant, in Spain. In this nationwide cohort study involving more than 3.1 million individuals, COVID-19 vaccine registries were tracked for groups that received either mRNA (Moderna, or Pfizer) or virus-vector (AstraZeneca) three-dose (with booster) and two-dose (without booster) and who have completed two-dose mRNA vaccination at least 3 months before study start date, The results of this study indicated only a 51.3% overall effectiveness for the mRNA boosters in preventing SARS-CoV-2 infection for up to 34 days after administration, with a higher level of effectiveness among females (52.6%) compared to males (49.8%). Higher effectiveness was reported among individuals in the 60-79 years age-group (60.4%) compared to only 55.8% in the 40-59 years age-group.
According to these researchers, the Spanish data reporting a substantially lower booster effectiveness against Omicron variant is consistent with other nationwide studies done in Qatar (49%), Scotland (57%), US (66%), and Canada (37%).
Although the effectiveness of boosters against the omicron variant is substantially lower, the investigation confirmed results from other previous studies that a third vaccine dose with AstraZeneca’s virus-vector based vaccine booster performed better (58.6%) compared to Moderna’s mRNA-1273 (52.5%) and Pfizer’s BNT162b2 booster (46.2%). Generally, higher effectiveness is reported in individuals vaccinated with virus-vector based vaccines, but reports of lower effectiveness of Pfizer’s mRNA vaccine boosters compared to the other mRNA vaccine (Moderna), or virus-inactivated vaccine (AstraZeneca) was reported by the researchers as inconsistent.
What then is an optimal initial vaccination course, follow-up booster for maximal and extended protection?
A key factor to delineate vaccination regime against COVID-19 is the effectiveness of the vaccine-booster regime to prevent vaccinated individuals from getting the COVID-19 disease as opposed to the risk of getting severe COVID-19 disease. It is in this key metric most published studies show two lines of diverging data. First, the mRNA booster effectiveness ranged poorly from 31.7 to 41.3 percent against confirmed COVID-19 infection 15 to 60 days after boosting, with protection lasting for about 6 months waning residual protection to a mere 2.8 to 14.6% against the infection. On the other hand, mRNA booster effectiveness against severe forms of COVID-19 disease was an impressive 87.2% for up to 6 months after boosting irrespective of the vaccine and booster combinations received by all vaccinated groups.
These study results reveal the limited effectiveness of vaccination with mRNA or virus-inactivated vaccines in preventing infection and appearance of COVID-19 disease, but vaccination appear to provide substantial protection from getting a severe form of the COVID-19 disease, with protection lasting for over 6 months.
“Leading Edge and Lagging Tail” of the COVID-19 vaccination
Large scale global vaccination against SARS-CoV-2, a new virus, yielded initial impressive results. However, propensity of SARS-CoV-2 virus to evolve into variants, together with the monovalent vaccines used as boosters targeting a specific variant has resulted in a situation where the viral variant generation became the leading edge and booster’s regime that follows as the lagging tail. As a result, booster regime remains in a catch-up mode, in that it is protective of the previous variants of the virus and not the newer variants at the leading edge of the pandemic onslaught. The basic presupposition in this approach that immunization against a previous variant may be protective of new variants turns out to be less successful based on the current published data on COVID-19.
To explain the outcome of COVID-19 immunization shortcomings in managing the pandemic, researchers are using a catchy phrase, “Original Antigenic Sin” or OAS for short, to immune system defense against the previous variants as the basis to afford protection against new and emerging variants. This brings up the question: how broad is the immunity gained through boosters? In the case of Influenza, those infected with the virus carry an immune system “memory” from the first infection, which when stimulated through boosting afford enhanced and continued immunity. This led to the concept of OAS. This concept is the basis to postulate that subsequent infections with similar influenza virus strains preferentially boost antibody response against the original strain. Although in some cases as in the influenza, the OAS formulation seems to be beneficial, it is unclear If it works in that fashion in the case of coronavirus-induced diseases.
When COVID-19 appeared globally, the most prevalent and potent Delta and Omicron viruses were encountered by our body immune system for the first time. The new infection creates an immune system memory specific to the infection, which with subsequent vaccination and booster further increases immunity, or so we believe is the case. If each new COVID-19 infection does not leave an immune memory, then the vaccination and boosters are fighting the old enemy and not the new one, which is evident from current published literature on booster effectiveness. It is our hope this does not become a limiting factor in the COVID-19 vaccination and booster regimen, where we remain stuck in the conundrum of fighting an older enemy while facing newer variants defenseless.