A year and a half ago, life was simple. Relatively speaking, that is. We had only one SARS-CoV-2 virus to deal with and though we did not know much about it, science bore down fast and hard. In a few months, the biotech and pharmaceutical industry achieved what previously would have taken years to, and that was to bring forth many vaccines. By the end of 2020, vaccination had started in the rich world, with the stated goal of providing “herd immunity” by the summer of 2021. And stock price of vaccine companies took off, Moderna (MRNA) and BioNTech (BNTX) being the most notable,

But, as the Scottish poet Robert Burns said, the best-laid plans of mice and men gang aft a-gley (often go wrong).

The virus began to mutate.

There was alpha, beta, and then the daddy of them, delta. The initial results showed that the vaccines maintained efficacy, though less than the original strains. Data from Israel in particular showed lower hospitalization and death among those vaccinated than among those not vaccinated. So far so good. But storm clouds are gathering, and it is worth taking a closer look at how our dams will hold.

1. Waning efficacy against Delta: As mentioned above, vaccination seemed at least initially to still provide protection. However, that efficacy seems to be waning. The latest study conducted by nference and the Mayo Clinic compared the effectiveness of the Pfizer and Moderna vaccines in the Mayo Clinic Health System over time from January to July.
   • The vaccines' effectiveness against infection dropped sharply in July when the Delta variant's prevalence in Minnesota had risen to over 70%.
   • Moderna was 76% effective against infection, and Pfizer was only 42% effective.
   • The study found similar results in other states. For example, in Florida, the risk of infection in July for people fully vaccinated with Moderna was about 60% lower than for people fully vaccinated with Pfizer
2. Low efficacy against Lambda and Gamma: Delta is not the only strain one has to contend with. Gamma strain was found in French Guinea to be resistant to vaccines. And so is Lambda, first found in Peru. Lambda is already in Houston, waiting to take over from Delta. How will vaccinations help?
3. Wither herd immunity? The mantra last year was herd immunity. Once 70% of the population was vaccinated, we would have herd immunity. Or so the party line went. With delta, gamma, and lambda, the concept may be dead. As the developer of the Astra Zeneca vaccine said:

Speaking at a UK parliamentary meeting on Tuesday, Sir Andrew Pollard, a professor of pediatric infection and immunity at the University of Oxford, said that achieving herd immunity is "not a possibility" now that the Delta variant is circulating.

"We know very clearly with coronavirus that this current variant, the Delta variant, will still infect people who have been vaccinated and that does mean that anyone who's still unvaccinated, at some point, will meet the virus," Pollard said.

He said it was unlikely that herd immunity will ever be reached, saying the next variant of the novel coronavirus will be "perhaps even better at transmitting in vaccinated populations."

4.  Will vaccines actually make the situation worse? So there may never be herd immunity, and vaccines look ineffective against some strains, and increasingly ineffective against delta. But can they make the situation worse? A study suggested that may happen.

"When most people are vaccinated, the vaccine-resistant strain has an advantage over the original strain," Simon Rella of the Institute of Science and Technology Austria, who worked on the study, told reporters.

"This means the vaccine-resistant strain spreads through the population faster at a time when most people are vaccinated."

This is likely to be especially true with a more transmissible variant such as the Delta variant, said Fyodor Kondrashov, also of the Institute of Science and Technology Austria.

"Generally, the more people are infected, the more the chances for vaccine resistance to emerge. So the more Delta is infectious, the more reason for concern," Kondrashov told reporters.

"By having a situation where you vaccinate everybody, a vaccine-resistant mutant actually gains a selective advantage."

5.  Execution, execution, execution: At present, we have this mix of a relatively vaccinated North America and Western Europe, and mostly unvaccinated Africa, Asia, and South/Latin America. The virus has all the time to mutate in both places under differing conditions, leading to a bizarre mix and match scenario. Unlike Influenza, there is not a single predominant strain that will last a year. There are simultaneously many strains, and it is impossible to vaccinate 8 billion people to every single variant continuously. The globe has been unable to vaccinate against the original strain a year and half into the pandemic. How will it be able to cope with ever-evolving strains and variants?

If the motto in real estate is location, location, location, in the business world it is execution, execution, execution. Where is the execution expertise to vaccinate 8 billion people, repeatedly? In remote parts of Congo in Africa, Archipelagos in Indonesia, Pampas in Argentina? In North Africa and Afghanistan/Pakistan where Islamic fundamentalists kill even polio workers?

6.  Follow the money: Vaccinating is expensive. Countries threw money at vaccines, hoping for the mythical herd immunity, thinking it was a one-time expenditure. The US alone spent a trillion dollars. Where will the money come from to vaccinate again and again and again? Even if Moderna and BioNTech give up patents, it is still expensive to manufacture, transport, store, and administer the vaccines. So, where will the money come from?

This article is not meant to be the musings of a nattering nabob of negativism. It is a hard look at the ground realities of the pandemic and the future of vaccines. And for the holders of vaccine stocks, which have reached astronomical levels. Maybe time to take your profits?