## Vaccine, Immunity and Reproduction Number R - 2020.05.04

**Why it takes so long to develop a corona vaccine?**

There is still no vaccine against the coronavirus. Development is in full swing worldwide, initial trials and clinical studies have already started. However, despite intensive research, it may still be some time before a vaccine hits the market. We explain why.

A vaccine is a medical trick. It is supposed to pretend to the body that it is infected with an aggressive pathogen such as SARS-CoV-2. If the deception succeeds, the immune system forms specific antibodies and T cells for virus defense. Vaccinations thus lead to the formation of an immune memory: If the same pathogen starts an infection again, the specific immune system can react directly and often there is no longer a disease.

However, this immunity does not exist for a lifetime against all pathogens. SARS-CoV-2, in particular, reports that people have contracted COVID-19 disease again. If this is confirmed, it will be difficult to develop an effective vaccine.

**When does a vaccine come against the virus?**

It usually takes many years to develop a vaccine. So it is almost always too late for a current outbreak. With COVID-19 everything should go much faster now.

The vaccine of the Jenner Institute at Oxford University currently appears to be the most advanced. Tests on rhesus monkeys show that it can actually protect against infection with SARS-CoV-2. Like other companies and institutes, including the Mainz-based company BioNTech, the English researchers have started a Phase I study to prove the safety of the vaccine. However, they are already preparing a phase 3 effectiveness study with 5,000 volunteers, the results of which could be available in the autumn. At the same time, the Indian Serum Institute wants to produce the vaccine. In the best case it would be quickly available, in the worst case the institute would make large losses. It is currently unclear whether the vaccine will deliver what it promises.

**SARS-Cov-2 and Immunity**

Are you immune after undergoing SARS-CoV-2 infection?

Initial studies have shown that people who have had SARS-CoV-2 infection develop specific antibodies that are directed against the N or S protein and are detectable on average about 5–12 days or 14 days after the onset of symptoms. Based on animal experiments on rhesus monkeys, previous findings on SARS and plausibility assumptions, experts assume that recovered patients have a very low risk of reinfection. It is unclear how regularly, robustly and permanently this immune status is built up. Experience with other coronavirus infections (SARS and MERS) suggests that immunity could last up to three years. To determine this more precisely, longitudinal serological studies are required that monitor patient immunity over a longer period of time.

**What is the reproduction number R and how important is it for assessing the situation?**

The number of reproductions describes how many people infect an infected person on average. It cannot be used alone as a measure of the effectiveness / necessity of measures. Also important are the absolute number of new infections every day and the severity of the illnesses. The absolute number of new infections must be small enough to enable effective contact person tracking and not to overload the capacities of intensive care beds.

At the beginning of a pandemic, there is the starting value R0 (also: basic reproductive number), which describes how many people are infected on average if the entire population is susceptible to the virus (because there is still no immunity in the population), yet Vaccine available and no infection control measures have yet been taken.

With SARS-CoV-2, R0 is between 2.4 and 3.3, which means that every infected person is infected with a little more than two to a little more than three people. Without countermeasures, the number of infections would increase exponentially and only stop when up to 70% of the population has gone through an infection or illness, i.e. is immune and can no longer spread the virus.

The number of reproductions can be reduced through infection protection measures. One speaks of a time-dependent reproduction number R (t). The following applies:

• If R is higher than 1, then increasing number of new infections every day, exponential increasing.

• If R = 1, then a constant number of new infections every day.

• If R is less than 1, then the number of new infections per day decreases.

With SARS-CoV-2, the goal is to keep the reproduction number stable below 1.

The number of reproductions can be determined on the basis of the data transmitted to the RKI on the confirmed cases. However, this data is available with a certain reporting delay. In order to compensate for this delay in reporting and to be able to indicate current values of R, a statistical procedure (so-called nowcasting) is implemented. However, nowcasting can only be used if the maximum reporting delay in an outbreak is known. This was the case in the current COVID 19 outbreak from the end of March. The nowcasting model was then adapted and validated over several days. The retrospective evaluation was first published online on April 9, 2020 as an article in Epidemiological Bulletin 17/2020 and then updated twice.