Avoid having ‘booster’ shots of the same vaccines—wait for the ‘souped up’ versions
CLINICAL MATTERS
Dr. Edsel Maurice T. Salvana
On Aug. 15, 2021, the Department of Health along with the Philippine Genome Center announced the latest variant detected in the Philippines. Lambda, also known as C.37, is a variant of interest first detected in Peru. Lambda subsequently spread to the rest of South America and from there made its way to other parts of the world.
The World Health Organization (WHO) has three tiers for tracking SARS-CoV-2 variants. The highest level are the “variants of concern” or VOCs. VOCs are SARS-CoV-2 variants with real-world evidence of increased transmissibility and/or decreased vaccine susceptibility and/or severity. There are currently four VOCs: Alpha (B.1.1.7, first described in the UK), Beta (B.1.351, first described in South Africa), Gamma (P.1, first described in Brazil), and Delta (B.1.617.2, first described in India.).
The next tier are the “variants of interest” or VOIs. These are variants with mutations that could potentially impact transmissibility and/or vaccine susceptibility and/or severity, but evidence is still being gathered whether this is the case in real life. There are currently four VOIs, including Lambda. VOIs can be upgraded to VOCs if the evidence shows higher transmission or decreased vaccine efficacy. They can also be downgraded to the next tier or even removed entirely if there is sufficient evidence that they do not exhibit any of the characteristics of VOCs. The latter occurred with Theta, or P.3, which was first described in the Philippines. After a period of observation, Theta did not turn out to have any significant deleterious effects and so it was removed from the list.
The last tier is the “Alerts for Further Monitoring,” a list that monitors variants that have the potential to become VOIs or VOCs. It may also be the tier to which former VOIs are downgraded if further monitoring is needed. Epsilon (B.1.427/B.1429, first described in the US) is a former VOI that has been downgraded to this tier because predicted decreases in vaccine efficacy have not materialized. The case of Epsilon is instructive because of earlier worries that Epsilon was going to be the next VOC, based on preliminary studies on the effect of its spike protein mutations on the vaccine. This is why it is always important that laboratory observations are validated against real world data, since in vitro studies are not necessarily reflective of real-world conditions.
Lambda was first described in December 2020 and designated a variant of interest in June 2021. It has some mutations in the spike protein, particularly L452Q, which may decrease vaccine efficacy. Some preprint articles have described increased evasion of the Lambda variant versus some vaccines, particularly Coronavac/Sinovac. Real world data, however, has not shown an extreme decrease in vaccine efficacy. Published data from Chile, where Coronavac/Sinovac is used extensively, and where Lambda makes up to one third of the circulating variants, have not shown a drastic decrease in protection against clinical disease or severe disease. In Peru, where up to 90 percent of circulating viruses are Lambda, the Sinopharm vaccine has shown preliminary efficacy in preventing death by as much as 94 percent. In contrast to the hype generated by the supposed “immune evasion” properties of Lambda, the United States Centers for Disease Control (CDC) does not even consider Lambda a Variant of Interest.
What does the detection of Lambda mean for the Philippines? First is that the threat of VOCs and VOIs is ever present from travelers. More than half of the representative sequences from COVID-19 positive Returning Overseas Filipinos (ROFs) intercepted during quarantine are variants of concern. Border control isn’t perfect, but it can slow down the entry of the different VOCs and VOIs as well as new variants of COVID-19. Second, there are still gaps in genomic surveillance, and these need to be addressed by casting a wider net and deploying sequencing capacity to more laboratories in the Philippines. Third is that there is clearly a lot of misinformation on social media and even mainstream media, which can cause undue panic if proper information is not forthcoming.
Lambda looks scary, but Delta is still scarier. What one does to prevent infection from Delta will work for Lambda. Getting vaccinated, wearing a mask with a face shield, and practicing public health standards work on all the variants.
As for misinformation, there is no truth to recent reports that some COVID-19 vaccines only protect for six months or eight months or one year. The long-term follow-up for the original Phase 3 clinical trials of the different COVID-19 vaccines are still ongoing. This is why the original regulatory approval for the different vaccines was only for emergency use. While the efficacy data already showed significant protection and safety against COVID-19 in the short term, long-term efficacy and safety data continue to be gathered.
Data being reported are of two types: laboratory measures of immunity and clinical efficacy. The laboratory-measured neutralizing antibody levels in response to the different vaccines are the easiest to measure. Antibody levels naturally decline over time if there is no exposure. It is not efficient for the body to maintain high antibody levels over time without a reason to do so. If there are sufficient memory B-cells generated, these can quickly churn out antibodies if there is exposure to COVID-19. Therefore, declining antibody levels do not necessarily mean protection is gone completely, since the body has already been “trained” to recognize SARS-CoV-2 and has a rapid mechanism for defending itself. Interpretation of studies dealing with lowering of antibody levels need to be done in the context of actual protection against disease. So far, studies in real life seem to confirm continued protection against severe disease for all the COVID-19 vaccines being used in our country. Whether protection against asymptomatic disease or clinical disease is going down as a result of decreased antibody levels, or because of the increasing proportion of variants of concern remains an open scientific question.
In addition, the cell-mediated T-cell immune component, which works against severe disease, seems to remain robust for now, even against the VOCs. Studies on boosters are ongoing, but aside from immunocompromised individuals (organ transplant patients or those with an equivalent level of immunosuppression), there is no strong consensus on the current need for boosters, and WHO does not recommend it at this time.
Finally, modified versions of some of the vaccines directed against the variants of concern have been developed and are in clinical trials. It is best to wait for these “souped-up” boosters rather than experimenting with boosters of old vaccines, which haven’t been adjusted against the variants. The current vaccines do work and will continue to protect against severe disease for the foreseeable future.