• P.K. Peterson

Vaccines vs. Variants: A Marathon Not a Sprint

“We need to keep an eye on the variants, but still I think we also have to trust the vaccine itself because we have evidence that it works.” - Adi Stern, evolutionary virologist, Tel Aviv University

“No marathon gets easier later. The halfway point only marks the end of the beginning.” - Joe Henderson, American runner, running coach, and writer

About 14 months ago the World Health Organization (WHO) declared that COVID-19 had become a pandemic, i.e., an infectious disease that was rapidly spreading globally. At that time, it was already obvious to some epidemiologists that SARS-CoV-2, the novel coronavirus that causes COVID-19, would be no pushover and that the race to defeat it was going to be a marathon, not a sprint. It was also clear to all the experts that the main weapon needed to end the pandemic would be a vaccine. But in March 2020, few, if any, experts predicted that we’d have a vaccine by the end of the year.

Today, we have not one but three highly effective and safe vaccines that have received Emergency Use Authorization (EUA) from the US Food & Drug Administration (FDA). And approximately 42% of adults in the U.S have been fully vaccinated.

SARS-CoV-2 is, however, an RNA virus, and RNA viruses mutate—that’s the way they operate. It therefore came as no surprise to the viral geneticists who were tracking the SARS-CoV-2 mRNA genome from the beginning of the pandemic that mutations were quickly emerging. Fortunately, most of these mutants (also called variants) were of no biological consequence. But by the end of 2020, mutants had emerged in the UK and South Africa that were considerably more contagious and possibly more lethal. (I addressed some of the variants in my January 6, 2021 Germ Gems post.) Consequently, concern also arose that the available vaccines would no longer protect against these mutants. In this Germ Gems post, I summarize where we are positioned in the “vaccines vs. variants marathon,” and I discuss several new strategies aimed at helping achieve the long-term goal—ending the COVID-19 pandemic.

Status of current COVID-19 vaccines. All three of the vaccines approved in the US (Pfizer-BioNTech, Moderna, and Janssen/Johnson & Johnson) have been proven to be phenomenally effective at preventing severe COVID-19 and safe.

In keeping with the focus on safety, usage of the vaccines is carefully monitored. For example, there was a brief pause in the use of the Janssen/J&J vaccine that was prompted by reports of an increased risk of a rare adverse event called thrombosis with thrombocytopenia syndrome (TTS), a condition that involves blood clots with low platelets.

Nearly all reports of this condition have been in adult women younger than 50 years old. At the time of the pause, this condition had occurred in only 6 of 7 million vaccinees. A review by the FDA concluded, however, that the benefits of the Janssen/J&J vaccine outweigh its known and potential risks. Nevertheless, women younger than 50 years old should be aware of the very rare but increased risk of this adverse event, and they should also bear in mind that there are other COVID-19 vaccine options available for which this risk has not been seen. (For more detailed information on vaccine side effects, I recommend Emily Mullin’s April 20, 2021 article in Smithsonian Magazine, “Experts Answer Eight Key Questions About COVID-19 Reactions.”)

Similar to the TTS associated with the Janssen/J&J vaccine, comparable side effects were observed with another adenovirus-vectored vaccine produced by Oxford University/AstraZeneca. To date, the FDA has not given EUA to AstraZeneca’s vaccine. Moreover, given that the US appears to have adequate supplies of the other three vaccines, it appears that AstraZeneca may not even seek EUA for its vaccine. The Oxford/AstraZeneca vaccine is, however, playing an important role outside the US, especially in the developing world.

While the three approved vaccines in the US have a high efficacy rate, they are not 100% effective. Therefore “breakthrough infections,” that is, COVID-19 infections in people who have been vaccinated, do occur and are expected. In the US, 0.01% of fully vaccinated people are known to have caught the virus through a breakthrough infection. Right now, experts agree that breakthrough infections are exceedingly rare and don’t require updated shots. It is possible, however, that down the line “booster” doses of vaccine may be recommended.

Enter the variants. A plethora of SARS-CoV-2 genetic variants have been identified since the outset of the COVID-19 pandemic. While most of these mutants aren’t more problematic than the original wildtype virus, several variants are being tracked carefully because they are more contagious, possibly more virulent, and some may have the ability to evade immunity conferred by COVID-19 vaccines.

Recently, the Centers for Disease Control and Prevention (CDC) and WHO developed a classification system of SARS-CoV-2 variants that conveys three levels of associated risk: “variant of interest,” “variant of concern,” and “variant of high consequence.” To date, none of the variants fits the third risk category. But the CDC is presently tracking the following variants of concern (VOC): B.1.1.7 variant, first identified in the UK (and currently circulating widely in the US); B.1.351 variant, first reported in South Africa; P1 variant, first detected in Japan and Brazil; and B.1.427 and B.1. 429 variants that have been spreading in California. (A multitude of other “homegrown variants” have been found in the US, but to date these are classified as “variants of interest.”)

In addition, the WHO and CDC recently added two other VOCs to the list: B.1.617.1 and B.1.617.2, variants that emerged in India. As you’re likely aware, India is currently overwhelmed by a marked increase in COVID-19 cases and deaths. While the reasons for the deterioration of the situation in India are complex, these viral mutants appear to play a role as the preliminary evidence has shown they are more transmissible than earlier strains of the virus. To add to the tragedy, India’s vaccine supplies are limited. Therefore, leaders in rural India are struggling to stretch their already thin vaccine supplies even farther.

Moreover, B.1.6.17 appears to be spreading. It was detected recently in nearby Thailand and further afield, in the UK. It was also identified for the first time in the US on May 14th, in an international traveler in Nebraska.

Vaccination protection against variants. A burning question that everyone who’s been vaccinated wants answered is, “Can the COVID-19 vaccine protect me against virus variants?” It appears that the mRNA vaccines are highly effective against the latest mutations that have emerged in India. But there is some evidence suggesting that the three vaccines in use in the US may not be quite as protective against certain other variants. Nonetheless, I agree with the argument made in a May 7, 2021 Medscape article “COVID-19 Variants are Innocent Until Proven Guilty,” that is, the current vaccines continue, for the most part, to be highly effective. The biggest challenge now is to get as many people vaccinated as quickly as possible to slow the pace of emergence of additional variants.

Obstacles in our path. Some naysayers contend that “herd” or community immunity (pegged at about 70% of people achieving immunity through vaccination or natural infection) can never be reached. Other experts, however, suggest we have reason to still give herd immunity a shot. In an article in the March 7, 2021 New Yorker, “What the Coronavirus Variants Mean for the End of the Pandemic,” Dr. Dhruv Khullar provides an optimistic assessment that even though SARS-CoV-2 is mutating, “we can still beat it, one vaccination at a time.” In support of this view, COVID-19 case counts and deaths continue to fall in the US in parallel with mounting numbers of vaccinated adults (to date, approximately 42% of the US population).

But at the same time that numbers of cases and deaths are receding in the US, the situation is not nearly so sanguine in many other countries. Because COVID-19 is a pandemic “nobody is safe until everyone in the world is immune.” Inequity-fueled catastrophic infection rates and death tolls are occurring in many low and middle-income countries (LMICs), where vaccines are scarce. This represents the single biggest roadblock to ending the pandemic.

There is good news, however. Other sources of vaccines, some produced by Russia and China, are available to people in LMICs. Also, additional vaccines that have shown promise are in development. Among 96 vaccine candidates in clinical trials, eight are intranasal vaccines. The advantage of a nasal vaccine is that it produces a strong immune response, involving secretory IgA antibodies, at the site of viral entry.

New vaccination strategies. In the US we are making steady progress and are on track to achieve President Biden’s most recent goal—administering at least one COVID-19 vaccine shot to 70% of the US adult population by July 4th. In addition, the FDA recently authorized the Pfizer-BioNTech vaccine for those 12-15 year olds and Moderna expects results soon from its own clinical trials involving adolescents ages 12-17. Moreover, the results from trials of the Pfizer-BiotechNTech and Moderna vaccines in children 6 months to 12 years-of-age are expected before the end of the year.

It is worrisome, however, that the pace of vaccinations of adults has slowed in recent weeks throughout the US. In an article, “Don’t Wait for Herd Immunity,” former Department of Homeland Security official Julliette Kayyem makes the case for doubling down in America’s vaccine-distribution program. She claims that the number of Americans who are resolutely anti-vaccine is small, “a stubborn 13%.” Therefore we need to find ways to provide more help for unvaccinated people who aren’t anti-vaxxers.

Removing practical obstacles to enable unvaccinated adults easy access to the vaccine is an achievable goal. In many cities, public health personnel are “beating the pavement” to vaccinate underserved people. Also, free rides to vaccination sites via Uber or Lyft or providing $100 incentives seem to be working. Other “stick rather than carrot” approaches include vaccine requirements for entry to college (now enforced by more than 300 US colleges) and for employment (“no jab, no job”).

Globally, we appear to have reached “heartbreak hill” in the COVID-19 marathon. But several strategies are afoot to bolster commitment to LMICs. For example, in February President Biden announced a plan to increase funding of Covax by $4 billion. (COVID-19 Vaccines Global Access, abbreviated “Covax,” is a worldwide initiative aimed at equitable access to COVID-19 vaccines directed by Gavi, the Vaccine Alliance, the Coalition for Epidemic Preparedness Innovations, and the WHO.) At the same time, discussions are underway with pharmaceutical companies to waive patent rights in LMICs. Equally promising are vaccines such as NVD-HXP-S and 2P that are in development with the potential to be real “game-changers” in LMICs. While a discussion of these vaccines is beyond the scope of this Germ Gems post, I recommend Carl Zimmer’s April 5, 2021 article in the New York Times, “Researchers Are Hatching a Low-Cost Coronavirus Vaccine” to those who might be interested.

In the recent article “One Vaccine to Rule them All,” Dr. James Hamblin asks, “What if a single vaccine could protect us against SARS, MERS, COVID-19, and every other coronavirus-related disease for ever and ever?” In February 2021, it was announced that the first human trials of a universal coronavirus vaccine are set to begin later this year. It appears that the aspirational goal of a universal vaccine that is active against all coronaviruses may be getting closer to reality. This past year, we’ve witnessed the astonishing success of SARS-CoV-2 vaccines. We’ve seen that when science, dedication, courage, and investments (by both the private and public sectors) are aligned, remarkable achievements are possible…perhaps even a universal coronavirus vaccine.

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Main Page images courtesy of Shuxian Hu, MD. Dr. Hu is a scientist in the Neuroimmunology Research Laboratory at the University of Minnesota.


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